LIJSTEN STUDIES HEMATOLOGIE

LIJSTEN STUDIES
HEMATOLOGIE
(juni 2014)
 Lopende studies
 Studies in voorbereiding
 Studies gesloten
Pagina 1 van 41
Lopende studies
met in- en exclusiecriteria (juni 2014)
_
Nummer
Leukemie
Omschrijving
Start UMCN Investigator
HOVON97
Azacitidine maintenance therapy in AML
29-11-2012
Huls G
1
HOVON100
Clofarabine in acute lymphoblastic leukemia in adults.
10-2-2011
Muus P
12
HOVON103
Addition of new drugs to standard induction
chemotherapy in AML and RAEB
29-3-2012
Muus P
8
HOVON132
Lenalidomide with remission-induction chemotherapy
and post-remission treatment in AML or high risk MDS
(18-65 years)
25-4-2014
Huls G
1
PLMA25
Allogeneic NK-cell therapy in AML
1-6-2011
Schaap N
6
PLMA33
The biology of ageing in relation to acute myeloid
leukemia (AML)
22-3-2013
Huls G
9
RLMA29 OCEAN
Observational study in patients with AML, MDS or CML
treated with azacitidine
13-12-2012
Huls G
17
HOVON105
Rituximab in primary CNS lymphoma
15-7-2013
Stevens W
2
HOVON120
Sequential zevalin versus observation in patients ≥ 60
years with newly diagnosed diffuse large B-NHL in CR
after R-CHOP or R-CHOP-like therapy
22-4-2014
Stevens W
0
HOVON89
Lenalidomide with or without erythropoietin and
granulocyte-colony stimulating factor in MDS
15-2-2010
Muus P
9
EU-MDS
EU-MDS registry
15-4-2008
MacKenzie M
44
17-2-2014
Huls G
0
Bortezomib and dexamethasone versus dexamethasone
alone followed by HDM and SCT in de novo amyloid light
chain (AL) amyloidosis
8-7-2013
Croockewit S
0
PSCT16
Vaccination with minor histocompatibility antigen-loaded
donor DC vaccines to boost graft-versus-tumor immunity
after partially T cell-depleted stem cell transplantation
19-12-2013
Schaap M
1
HOVON115
Double umbilical cord blood transplantation
28-11-2012
Schaap M
0
XEN/TG-001
T-Guard for acute GVHD
vd Velden W
3
Accrual
Lymfomen
MDS
Oral azacitidine in subjects with RBC transfusionAZA-MDS-003 dependent anemia and thrombocytopenia due to
IPSS lower-risk MDS
MM
HOVON104
SCT
2-1-2014
Pagina 2 van 41
Lopende studies
met in- en exclusiecriteria (juni 2014)
Supportive Care
Empirical versus pre-emptive antifungal therapy of
patients treated for haematological malignancies or
receiving an allogeneic stem cell transplant
1-4-2012
vd Velden W
42
PRO-RBDD
Rare bleeding disorder registry (PRO-RBDD)
21-8-2013
Laros B/ Brons P
18
RISE
Response to DDAVP in moderate/mild Hemophillia A
patients
6-8-2013
Laros B/ Brons P
37
VWD TEST
Implementatie nieuwe diagnostiek test voor de screening
en follow up van de ziekte van Von Willebrand
19-8-2013
Laros B/ Brons P
68
RPNH01
PNH registratie
15-4-2009
Muus P
108
RPNH02
Eculizumab treatment at home in PNH patients
20-2-2012
Muus P
36
EORTC
65091-06093
Stolling
PNH
Pagina 3 van 41
Studies in voorbereiding
met in- en exclusiecriteria (juni 2014)
_
Nummer
Omschrijving
Nilotinib with PegIntron in CML with suboptimal
NordDutchCML009 molecular response or stable detectable MRD after at
least 2 years of imatinib treatment
Investigator
Startdatum
Radboudumc
Blijlevens N
07 - 2014
Blijlevens N
07 - 2014
SC29
Enteral versus parenteral nutrition in SCT patients with
chemotherapy-induced gastro-intestinal mucositis
SC30
Farmacokinetiek en veiligheid van micafungin twee
maal per week ten opzichte van dagelijkse toediening
Velden vd W
gedurende 8 dagen bij patiÃ«nten die een risico hebben
op een schimmelinfectie
AC220-007
Quizartinib (AC220) monotherapy versus salvage
chemotherapy in FLT3-ITD+ AML refractory to or
relapsed after first-line treatment with or without HSCT
Huls G
08 - 2014
PLMA34
10-day decitabine, fludarabine and 2 Gray TBI as
conditioning strategy for poor and very poor risk AML in
CR1
Schaap M
08 - 2014
EORTC 1301AML21
10-day decitabine versus conventional chemotherapy
(“3+7”) followed by allografting in AML patients ≥ 60
years
Huls G
10 - 2014
OPTI-CLOT
prospective
Peri-operative pharmacokinetic-guided dosing of
clotting factor in hemophilia
Laros B
07 - 2014
EU-HASS
European haemophilia safety surveillance system –
EUHASS registry
Laros B
07 - 2014
Studies recent gesloten
(juni 2014)
_
Nummer
Omschrijving
CLDE225X2203/ Oral LDE225 in adult patients with relapsed/refractory
PLMA32
acute leukemia
HOVON95
Comparison VMP with high dose Melphalan in newly
diagnosed MM
Investigator
Inclusie
Huls G
2
Croockewit S
18
Pagina 4 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
HOVON 97 – PLMA30
Bron: HO97 AML protocol 16AUG2012.pdf
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Pagina 5 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
HOVON 103 – PLMA28
Bron: protocol HO103 tosedostat version 28may10 .pdf
Pagina 6 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
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Pagina 7 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
HOVON100 – PLLA11
Bron: HO100 PRO 07JUL2011.pdf
Pagina 8 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
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Pagina 9 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
PLMA25 ON HOLD
Bron: Samenvatting PLMA25 versie 1.0.pdf
Inclusion Criteria
 AML patients >65 year of age
 Absence of a HLA-Cw ligand for an inhibitory KIR (i.e. homozygous Cw group 1 or 2)
 CR after first line standard chemotherapy
 CR after second line chemotherapy
 WHO performance 0-1
 Life expectancy > 6 months
 Written informed consent
.
Exclusion criteria
 Patients candidates for SCT
 Progressive disease, no change or only minor response following induction and consolidation
therapy
 Patients on immunosuppressive drugs
 Presence of HLA-antibodies
 Patients with active infections (viral, bacterial or fungal) that requires specific therapy. Acute antiinfectious therapy must have been completed within 14 days prior to study treatment
 Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure
or symptomatic ischemic heart disease
 Severe pulmonary dysfunction (WHO III-IV)
 Severe renal dysfunction (serum creatinine > 3 times normal level)
 Severe hepatic dysfunction (serum bilirubin or transaminases > 3 times normal level)
 Severe neurological or psychiatric disease
terug naar overzicht
Pagina 10 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
PLMA32 ON HOLD
Bron: prot version 00 28jan2013
Inclusion criteria
Patients eligible for inclusion in this study have to meet all of the following criteria:
1. Written informed consent must be obtained prior to any screening procedures.
2. Male or female adult patients (≥18 years).
3. Histological or cytological diagnosis of either :
a. Relapsed or primary refractory non-M3 acute myeloid leukemia (AML), by the World
Health Organization (WHO) classification (irrespective of the number of prior
regimens), either de novo or secondary [i.e., to myelodysplastic syndrome (MDS),
myeloproliferative neoplasm or previous chemotherapy for another neoplasia].
b. Untreated AML in patients ≥ 65 years of age, if they are not candidates for standard
induction chemotherapy.
c. Relapsed or refractory non-T-cell acute lymphoblastic leukemia (ALL) by WHO
classification. Philadelphia chromosome positive (Ph+) ALL patients who have
demonstrated resistance to tyrosine kinase inhibitor therapy.
4. White blood cell count (WBC) ≤ 50 x 109/L. Prior cytoreductive measures, such as
leukapheresis, hydroxiurea, or corticosteroids are allowed.
5. Performance status corresponding to ECOG (WHO) score of 0, 1 or 2.
6. Adequate renal function as defined by the following:
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN).
7. Adequate liver function as defined by:
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) range of values, unless due to
elevated indirect bilirubin (i.e. Gilbert’s syndrome or hemolysis).
• Serum alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT)
≤ 3 x ULN.
• Albumin ≥ 2.0 g/dl.
• Alkaline phosphatase (AP) ≤ 2.5 x ULN.
8. Serum CK ≤ 1.5 x ULN.
9. At least 2 weeks since end of last leukemia therapy (except for hydroxyurea, which is
allowed if clinically indicated to lower blasts counts, but should be stopped after 2 weeks
of receiving study drug, and corticosteroids, which are allowed but should be stopped
upon starting treatment drug), given recovery to grade ≤ 1 from any non-hematological toxicity derived from
previous treatment (excluding alopecia of any grade and grade ≤ 2
Pagina 11 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
peripheral neuropathy). Only low oral stable doses of corticosteroid (≤10mg/day
prednisone or equivalent) will be permitted during the course of the study.
Exclusion criteria
Patients eligible for this study must not meet any of the following criteria at screening:
1. Allogeneic SCT within the last 4 months and/or active GVHD, or autologous SCT within
the last 4 weeks.
2. Active CNS leukemic involvement.
3. Major surgery within 2 weeks of initiation of study medication.
4. Concurrent uncontrolled medical conditions that may interfere or potentially affect the
interpretation of the study.
5. Unable to take oral drugs, or lack of physical integrity of the upper gastrointestinal tract,
or known malabsorption syndromes.
6. Patients with unresolved diarrhea > CTCAE grade 2.
7. Patients who have previously been treated with systemic LDE225 or with other Hh
pathway inhibitors.
8. Patients who have neuromuscular disorders (i.e. inflammatory myopathies, muscular
dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on
concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as
HMG CoA inhibitors (statins), clofibrate and gemfibrozil. Pravastatin may be used if
necessary, with extra caution.
9. Patients who are planning on embarking on new physical activities, such as strenuous
exercise, that can result in significant increases in plasma CK levels while on study
treatment. Strenuous muscular activity MUST be avoided within 1 week of blood tests
during the study.
10. Patient has history of cardiac dysfunction including any of the following:
a. Myocardial infarction documented by elevated cardiac enzymes or persistent regional
wall abnormalities on assessment of LVEF function within the last six months.
b. History of documented congestive heart failure (New York Association functional
classification III-IV).
c. Documented cardiomyopathy.
d. Familial history of long QT syndrome.
11. Patient has active cardiac disease including any of the following:
a. QTc interval corrected for heart rate using Fridericia’s formula [QTcF] > 450 msec
for males and > 470 msec for females on the screening ECG.
b. Angina pectoris that requires the use of anti-anginal medication.
Pagina 12 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
c. Ventricular arrhythmias except for benign premature ventricular contractions.
d. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with
medication.
e. Conduction abnormality requiring a pacemaker.
f. Valvular disease with documented compromise in cardiac function.
g. Symptomatic pericarditis.
12. Use of other investigational drugs within 30 days or 5 half-lives of initiation of study
medication, whichever is longer.
13. Patients who are receiving treatment with medications known to be moderate and strong
inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that
have narrow therapeutic index, and that cannot be discontinued before starting treatment
with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued at
least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment
with LDE225.
14. Patients are excluded if the use of warfarin (substrate of CYP2C9) is necessary and cannot
be substituted since LDE225 is competitive inhibitor of CYP2C9 based on in vitro data.
15. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female
after conception and until the termination of gestation, confirmed by a positive hCG
laboratory test (> 5 mIU/mL).
16. Patients who are not willing to apply highly effective contraception during the study and
through the duration as defined below after the final dose of study treatment.
Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, must use highly effective contraception during the study and through
6 months after the final dose of study treatment. Highly effective contraception is defined
as either:
• Total abstinence: When this is in line with the preferred and usual lifestyle of the
patient. Periodic abstinence (i.e., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception.
• Sterilization: Patient has had surgical bilateral oophorectomy (with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment. In
case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment.
• Male partner sterilization (with the appropriate post-vasectomy documentation of the
absence of sperm in the ejaculate). [For female study patients, the vasectomised male
partner should be the sole partner for that patient].
• Use a combination of the following (both a+b):
Pagina 13 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
a. Placement of a non-hormonal intrauterine device (IUD) or non-hormonal
intrauterine system (IUS).
b. Barrier method of contraception: Condom or Occlusive cap (diaphragm or
cervical vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
Note: Hormonal contraception methods (i.e. oral, injected, implanted) are not
allowed as it cannot be ruled out that the study drug decreases the effectiveness of
hormonal contraception.
Note: Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e.
age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea
with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral
oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by
follow up hormone level assessment is she considered not of child bearing potential.
Male patient must use highly effective (double barrier) methods of contraception (i.e.,
spermicidal gel plus condom) for the entire duration of the study, and continuing using
contraception and refrain from fathering a child for 6 months following the study drug. A
condom is required to be used also by vasectomized men in order to prevent delivery of the
study treatment via seminal fluid.
17. Known HIV positivity.
18. Patients unwilling or unable to comply with the protocol.
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Pagina 14 van 41
Lijsten studies
met in- en exclusiecriteria (uni 2014)
PLMA35
- HOVONI32
Bron: HO132 Protocol v4 05MAR14
8.1 Eligibility criteria for registration/randomization
I
All patients must be registered/ randomized before start of treatment and must meet all of the
following eligibility criteria.
8.1.1 Inclusion criteria
.
.
Age 18-65 years, inclusive
Patients with
a diagnosis of AML and related precursor neoplasms according to WHO 2008
classification (excluding acute promyelocytic leukemia) including secondary AML
(after an antecedent hematological disease (e.9. MDS) and therapy-related
AML), or
acute leukemia's of ambiguous lineage according to WHO 2008 or
a diagnosis of refractory anemia with excess of blasts (MDS) and IPSS-R score >
4.5
WHO performance status O, 1 or 2
Sampled bone marrow and/ blood cells at diagnosis for centralized molecular analysis,
MRD evaluation and biobanking, unless in case of a dry marrow tap with no possibility
to collect marrow cells. ln cases of marrow tap failure only blood cells will be sampled.
s indicated by the
Adequate renal and hepatic
following laboratory values:
Serum creatinine =1.0 mg/dL (=88.2 pmol/L); if serum creatinine >1.0 mg/dL
(>88.7 pmol/L), then the estimated glomerular filtration rate (GFR) must be >60
ml/min/1 .73 m2 as calculated by the Modification of Diet in Renal Disease
equation where Predicted GFR (ml/minll.73 m2) - 186 x (Serum Creatinine in
mg/dl)-1 .154x (age in years)-0.203x(0.742 if patient isfemale) x(1.212 if patient is
black)
NOTE: if serum creatinine is measured in umol/L, recalculate it in mg/dl
according to the equation: 1 mg/dL = 88.7 umol/L) and use above mentioned
formula.
Serum bilirubin =2.5 x upper limit of normal (ULN)
Aspartate transaminase (AST) = 2.5 x ULN
Alanine transaminase (ALT) = 2.5 x ULN
Alkaline phosphatase = 2.5 x ULN
Written informed consent
Ability and willingness to adhere to the lenalidomide Pregnancy Prevention Program
o
o
o
¡
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functions
o
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o
o
o
o
8.1.2 Exclusion criteria
.
.
.
.
Previous therapy with lenalidomide
Acute promyelocytic leukemia
Myeloproliferative neoplasia
Previous treatment for AML or high risk MDS (IPSS-R
t
4.5), except hydroxyurea
Pagina 15 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
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Concurrent history of active malignancy in two past years prior to diagnosis except for:
o basal and squamous cell carcinoma of the skin
o in situ carcinoma of the cervix
Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes,
infection, hypertension, pulmonary disease etcetera)
Cardiac dysfunction as defined by:
o Myocardial infarction within the last 6 months of study entry, or
o Reduced left ventricular function with an ejection fraction < 50% as measured by
o MUG scan or echocardiogram or
o Unstable angina, or
o Unstable cardiac arrhythmias
Pregnant or lactating females
Unwilling or not capable to use effective means of birth control
Any psychological, familial, sociological and geographical condition potentially
hampering compliance with the study protocol and follow-up schedule
8.2 Eligibility criteria for randomization 2a (Part B)
Eligibility criteria for post-transplantation lenalidomide for part B (after cycle III or autoHSCT)
The second randomization = 4 months after start chemotherapy cycle III or start conditioning
autoHSCT.
8.2.1 Inclusion criteria
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CR or CRi
Absolute neutrophil count (ANC) = 1.5 x 109/L
Platelet count = 75 x 109/L
Serum creatinine clearance = 30 ml/min
Total bilirubin = 2.5 x ULN
AST = 2.5 x ULN
ALT = 2.5 x ULN
8.2.2 Exclusion criteria
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Severe cardiac dysfunction (NYHA classification II-IV, see appendix G)
Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix F)
Severe neurological or psychiatric disease
Serious active infections
Previous serious toxicities related to the use of lenalidomide
CMV reactivation, which is not responsive to first line valganciclovir
Pagina 16 van 41
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met in- en exclusiecriteria (juni 2014)
RLMA29 – OCEAN
Bron: Protocol_NIPMS-VZ-NL-001_Final version 3_dated 20120223_signed.pdf
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Pagina 17 van 41
Lijsten studies
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PLYN37 – HOVON90
Bron: Samenvatting Hovon90 juli 2010.doc
Voornaamste inclusiecriteria
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Leeftijd: 18-60 jaar
Alle stadia, inclusief stadium I met bulky disease (≥ 7.5 cm)
Bewezen histologische diagnose van perifeer T cel NHL van de volgende WHO (Engels)
gedefinieerde typen:
Peripheral T-cell lymphoma PTCL-NOS
Angioimmunoblastic T cell lymphoma
Intestinal T/NK-cell lymphoma (± enteropathy)
Hepatosplenic gamma-delta lymphoma
Subcutaneous panniculitis-like PTCL
T/NK cel lymfoom, neustype
Performance status: ECOG 0 - 2 (Karnofsky index: 60 - 100%). ECOG 3 mag als veroorzaakt
door het NHL
Meetbare ziekte
Schriftelijke toestemming van de patiënt
Levensverwachting van 3 maanden of meer
Voornaamste exclusiecriteria
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Stadium I met IPI 0 zonder bulk
Al gestarte therapie
Ernstige bijkomende ziekte of orgaanschade, met name:
- Hartschade (NYHA class II-IV; LVEF <45%)
- Longschade (FeV1<50% or DC <50%)
- Nierfunctie: creatinine >2 maal bovenste referentiewaarde, tenzij veroorzaakt door NHL
- Lever: bilirubin >2 maal bovenste referentiewaarde, tenzij veroorzaakt door NHL
- Oncontroleerbare diabetes mellitus (prefase behandeling met prednison!)
Andere typen T cel maligniteiten
Centraal zenuwstelsel betrokkenheid
Bekende overgevoeligheid voor de te gebruiken medicatie, vooral muizen- of chimere antistoffen
Oncontroleerbare astma of allergie
Bekende HIV-positiviteit
Actieve hepatitis infectie, actieve CMV infectie, actieve systemische schimmel infectie, actieve
infectie met mycobacterium tuberculosis of atypische tuberculose
Twijfel aan de compliantie van de patiënt
Gelijktijdige deelname aan een andere studie
Eerdere chemo- of radiotherapie voor een maligniteit
Andere bijkomende maligniteit (anamnese van kanker gedurende de laatste 5
jaar, behalve basaalcelcarcinoom van de huid of stadium 0 cervixcarcinoom)
Wanneer andere eligibility criteria niet passen
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Pagina 18 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
PLYN38 – HOVON91
Bron: Samenvatting Hovon 91 maart 2011.doc
Inclusiecriteria
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Leeftijd: 61 - 80 jaar
Alle risico groepen, inclusief stadium I met bulk (≥ 7.5 cm) en stadia II tot IV, behalve stadium I
N zonder bulk en zonder IPI risk factor anders dan de leeftijd > 60 jaar (LDH, Performance,
meer dan 1 extranodale lokalisatie)
histologische bewezen diagnose van perifeer T cel NHL van de volgende WHO 2008
classificatie gedefinieerde typen:
o Peripheral T-cell lymphoma PTCL-NOS
 Lennert’s lymphoma
 T-zone lymphoma
 T-immunoblastic variant
 Perifollicular/follicular variant
o T-cell lymphoma of the AIL type
o Extranodal NK/T-cell lymphoma, nasal type
o Intestinal T/NK-cell lymphoma (± enteropathy)
o Hepatosplenic T-cell lymphoma
o Subcutaneous panniculitis-like PTCL
Performance status: ECOG 0 - 2 (Karnofsky index: 60 - 100%). ECOG 3 mag als veroorzaakt
door het NHL
Meetbare ziekte
Schriftelijke toestemming van de patient
Exclusiecriteria
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Stadium I N met IPI 0 (behalve leeftijd >60 jaar) zonder bulk
al geïnitieerde lymfoom behandeling (met uitzondering van de pre-fase behandeling)
Ernstige bijkomende ziekte of orgaanschade, met name:
o Cardiaal (angina pectoris CCS>2, NYHA class II-IV; LVEF <45%)
o Pulmonaal (FeV1<50% or DC <50%)
o Renaal: kreatinine >2 maal bovenste referentiewaarde, tenzij veroorzaakt door NHL
o Lever: bilirubine >2 maal bovenste referentiewaarde, tenzij veroorzaakt door NHL
o Oncontroleerbare diabetes mellitus (prefase behandeling met prednison!)
Trombo's <100 x 109/l, leukocyten <2,5 x 109/l
Beenmergbetrokkenheid >25%
Bekende overgevoeligheid voor de te gebruiken medicatie, vooral muizen- of chimere antistoffen
Primair leukemisch lymfoom
Bekende HIV-positiviteit
Actieve hepatitis infectie, actieve CMV infectie, actieve systemische schimmel infectie, actieve
infectie met mycobacterium tuberculosis of atypische tuberculose
Twijfel aan de compliantie van de patient
Gelijktijdige deelname aan een andere studie
Eerdere chemo- of radiotherapie voor een maligniteit
Andere bijkomende maligniteit (anamnese van kanker gedurende de laatste 5jaar, behalve
basaal carcinoom van de huid of stadium 0 cervix carcinoom)
terug naar overzicht
Pagina 19 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)
PLYN40 / HOVON98
Bron: in- en exclusiecriteria & samenvatting PLYN40 versie 1.1.doc
Inclusiecriteria
1. CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original diagnosis. If an evaluable biopsy or
fine needle aspiration (FNA) is performed prior to enrolment to the study it must confirm CD20 positive
DLBCL or grade 3b FL. Note: If evidence emerges that the binding of the immunohistochemical antibody
to CD20 can be blocked by rituximab, demonstration of CD20 positivity in the repeat biopsy/FNA will not
be required.
2. Refractory to, or relapsed following, first-line treatment with rituximab concurrently with anthracycline- or
anthracenedione-based chemotherapy.
Relapse is defined as:

Biopsy (preferred) or FNA confirmed DLBCL or grade 3b FL after a complete response (CR) or
unconfirmed complete response (CRu). However, for subjects relapsing during first-line treatment,
biopsy/FNA reconfirmation of the lymphoma is recommended but not mandatory.
Subjects must have received rituximab concurrently with at least 6 cycles of chemotherapy.
However, subjects with stage I/II disease will be eligible if they have received rituximab
concurrently with at least 3 cycles of chemotherapy and definitive involved-field radiation therapy#.
Refractory disease must fulfill one of the following:
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continuing partial response (PR) from termination of first-line treatment. It is strongly
recommended the lymphoma be reconfirmed by biopsy (preferred) or FNA, however, if these
procedures are deemed to be inappropriate, then HOVON may determine eligibility following
review of the imaging results and disease history.
Subjects must have received rituximab concurrently with at least 6 cycles of chemotherapy.
However, subjects with stage I/II disease will be eligible if they have received rituximab
concurrently with at least 3 cycles of chemotherapy and definitive involved-field radiation therapy#.

continuing stable disease (SD) from termination of first-line treatment. Reconfirmation of the
lymphoma by biopsy (preferred) or FNA is recommended but not mandatory.
Subjects must have received rituximab concurrently with at least 3 cycles of chemotherapy#.

progressive disease (PD). Biopsy or FNA reconfirmation of the lymphoma is recommended but
not mandatory.
Note: Disease response to first-line treatment is recommended to be determined according to Revised
Response Criteria for Malignant Lymphoma [Fout! Verwijzingsbron niet gevonden., 2007] or
nternational Workshop Response criteria for NHL [Fout! Verwijzingsbron niet gevonden., 1999]. For
guidance on the adequacy of dosing of rituximab during first-line therapy refer to the SPM.
3. Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical
tumor sites.
4. CT scan showing at least:

2 or more clearly demarcated lesions/nodes with a long axis >1.5cm and short axis 1.0cm
OR

1 clearly demarcated lesion/node with a long axis >2.0cm and short axis 1.0cm.
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Vervolg Inclusiecriteria:
5. Age ≥18
6. ECOG performance status 0, 1, or 2.
7. Eligible for high dose chemotherapy and ASCT.
8. Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not
contraindicate study participation.*
9. Signed written informed consent.
#
Eligibility of subjects treated with an intensive chemotherapy regimen will be determined by HOVON.
Exclusiecriteria
1. Any previous cancer therapy for the lymphoma, with the exception of:

First-line treatment with rituximab and an anthracycline- or anthracenedione-based chemotherapy.

Monotherapy rituximab, dosed prior to first-line rituximab combined with chemotherapy, or as
maintenance therapy.

Radiotherapy as part of the first-line treatment plan.

Radiotherapy to a limited field at a maximum dose of ≤10Gy to control life-threatening symptoms.

Prophylactic testicular radiotherapy for testicular lymphoma.

Intrathecal chemotherapy for the prophylaxis of CNS disease.
2. Received any of the following treatments within two weeks prior to start of study therapy (unless otherwise
stated):

Anti-cancer cytotoxics (e.g. alkylating agents, anti-metabolites, purine analogues)

Radiotherapy unless it is to a limited field at a maximum dose of ≤10Gy to control life-threatening
symptoms.
3. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half
lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other
interventional clinical study unless in the opinion of the investigator it does not contraindicate participation
in this study.*
4. Planned post-randomisation glucocorticoid therapy, unless

specified by the protocol

administered in doses 1mg/kg/day prednisolone (or equivalent dose of other glucocorticoid-refer to
the SPM for glucocorticoid equivalent doses)

administered as inhalation therapy for mild COPD or asthma.
5. History of significant cerebrovascular disease or event with significant symptoms or sequelae, unless in
the opinion of the investigator it does not contraindicate participation in the study.*
6. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six
months prior to randomisation, congestive heart failure (NYHA III-IV), a current LVEF of <40%, and
arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction
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Vervolg Exclusiecriteria:
7. abnormalities, unless in the opinion of the investigator it does not contraindicate participation in the
study.*
8. Significant concurrent, uncontrolled medical condition that in the opinion of the investigator
contraindicates participation in this study.*
9. Known lymphoma involvement of the CNS.
10. Known or suspected hypersensitivity to study treatments that in the opinion of the investigator
contraindicates their participation.*
11. Known HIV positivity.
12. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for
HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive
the subject will be excluded.
13. Active hepatitis C infection.
14. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such
as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis.
15. Other past or current malignancy within 2 years prior to randomization unless in the opinion of the
investigator it does not contraindicate participation in the study. Subjects who have been free of
malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer, or
successfully treated in situ carcinoma, are eligible.*
16. Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.
17. Screening laboratory values:

platelets <100x109/L (unless due to lymphoma involvement of the bone marrow)

neutrophils <1.5x109/L (unless due to lymphoma involvement of the bone marrow)

creatinine >2.0 times upper normal limit (unless due to lymphoma or unless creatinine clearance
>60mL/min)

total bilirubin >1.5 times upper normal limit (unless due to lymphoma or a known history of Gilbert’s
disease)

ALT >2.5 times upper normal limit (unless due to lymphoma)

alkaline phosphatase >2.5 times upper normal limit (unless due to lymphoma )
18. Subjects known or suspected of being unable to comply with the study protocol.
19. Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at
screening.
20. Women of childbearing potential, including women whose last menstrual period was less than one year
prior to screening, unable or unwilling to use adequate contraception from study start to one year after the
last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine
device, double barrier method or total abstinence.
21. Male subjects unable or unwilling to use adequate contraception methods from study start to one year
after the last dose of protocol therapy.
*The GSK Medical Monitor is available to discuss subject eligibility for all criteria
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PLYN41 – HOVON105
Bron: ho105-pro-17dec2012
Inclusion criteria
Patients with a histologically confirmed diagnosis of CD20 positive DLBCL based upon a
representative histology specimen of brain biopsy according to the WHO classification
(see appendix A):
OR
Patients with a diagnosis of PCNSL based on MRI evidence of brain parenchymal lesion
showing homogeneous contrast enhancement suspect for lymphoma
AND
o Unequivocal morphological and/or immunophenotypical evidence of CSF
CD20 + large cell lymphoma
o AND/OR Unequivocal morphological and/or immunophenotypical evidence of CD20 + large cell
lymphoma in vitreous fluid
OR
Patients with unequivocal morphological and/or immunophenotypical evidence of CD20 +
large cell lymphoma in vitreous fluid AND CSF but without a brain parenchymal lesion
 Age 18-70 years inclusive
 Performance status with or without administration of steroids WHO/ECOG 0 – 3 (see
appendix D)
 Written informed consent
Exclusion criteria
 Evidence of systemic lymphoma
 History of intolerance of exogenous protein administration
 Severe cardiac dysfunction (NYHA classification III-IV, appendix G, or LVEF < 45%)
Congestive heart failure or symptomatic coronary artery disease or cardiac arythmias not
well controlled with medication
 Severe pulmonary dysfunction (vital capacity or diffusion capacity < 50% of predicted
value)
 Significant hepatic dysfunction (bilirubin or transaminase = 2.5 x upper normal limit) at
Screening.
 Significant renal dysfunction (serum creatinine =150 .mol/l or clearance < 60 ml/min) at
Screening
 Presence of “third space fluid”, such as pleural effusion or ascites
 Prior cranial radiotherapy
 Active uncontrolled infection
 HIV-positivity
 (EBV positive) post-transplant lymphoproliferative disorder
 Untreated hepatitis B infection (inclusion is possible if adequate antiviral medication e.g.
lamivudine or alternative is started and continued for the duration of the trial)
 Positive pregnancy test in women of reproductive potential
 Lactating women
 Unable or unwilling to use adequate contraceptive methods (all men, pre-menopausal
women) until 12 months after last chemotherapy treatment
 Any psychological, familial, sociological or geographical condition potentially hampering
compliance with the study protocol and follow-up schedule
 An active malignancy, that is expected to require treatment with chemotherapy within one
year, or results in a life expectancy less than one year.
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PMDS27 – HOVON89
Bron: PMDS27_EligibilityCriteria_HOVON89_14dec2011.pdf
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PLYN42 - HOVON120
Bron: Protocol Number: SPI-ZEV-11-301, Amendment 2, 30 September 2012
6.1 Inclusion Criteria
Individual patients may be included only once in the study.
All of the following criteria have to be met for inclusion of a patient into the study:
1. Patient is 60-years of age or older at time of randomization
2. Histologically confirmed Ann Arbor stage II, III, or IV DLBCL; or FL Grade 3B
according to the WHO classification 2008 (from initial diagnosis made prior to starting
R-chemotherapy).
3. An H&E stained slide and unstained slides must be available for confirmatory pathology
review, as per the separate Pathology Guidance document. Patients may be randomized
based on the local diagnosis..
4. Presence of at least one IPI risk factor. The aaIPI is defined by one point for each factor:
a. LDH > upper limit of normal (ULN);
b. Stage III or IV; and
c. WHO/ECOG performance status >1.
5. First-line treatment must have been 6 cycles of standard R-CHOP or R-CHOP-like
chemotherapy (e.g. R-CHOP21, R-CHOP14, or DA-EPOCH-R). Patients who received
pre-phase therapy for the purpose of improving performance status prior to initiating RCHOP
are eligible. Standard dose reductions for toxicity are allowed.
6. Complete remission (CR) according to the Revised Response Criteria for Malignant
Lymphoma [22] (Appendix 2) after first-line treatment.
a. Diagnostic CT scans with contrast of chest, abdomen, and pelvis must have
been performed within 8 weeks after the first dose of the last cycle of
R-chemotherapy. PET-CTs obtained elsewhere before and after R-CHOP are
acceptable for evaluating response to R-CHOP, but a diagnostic CT prerandomization
is requested as reference for post randomization interval
change. A neck CT will be applicable if the patient had involvement of the
neck region by palpation / physical examination at initial diagnosis. The CT
portion of an FDG PET that includes the neck will be acceptable if the neck
had involvement.
b. A negative FDG-PET scan performed within 8 weeks after the first dose of
the last cycle of R-chemotherapy and confirming CR, with negative defined as
a score of 1-3 on the Deauville 5-point scale (Appendix 3) used to quantify
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radionucleotide density in PET scans as determined locally [23]. PET
positive/indeterminate lesions which are confirmed on biopsy to harbor no
active lymphoma will be considered negative for determination of CR status.
c. If positive bone marrow involvement at initial diagnosis the patient must have
a negative bone marrow biopsy following R-chemotherapy to confirm the CR.
7. WHO/ECOG performance status of 0, 1 or 2.
8. Adequate hematopoietic functions unsupported by transfusion within the last 2 weeks:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, Hemoglobin (Hgb) ≥ 9 g/dL, Platelets ≥
100 x 109/L. Patients with blood counts close to recovery towards these values after RCHOP
should be discussed with the study Medical Monitor prior to randomization, but
blood counts must have met these thresholds prior to treatment with Y-90 Zevalin.
9. In patients who had a post R-chemotherapy bone marrow biopsy performed, the marrow
must show cellularity > 15%. For patients without a post R-chemotherapy bone marrow
biopsy (i.e. those patients with negative marrow at diagnosis), a repeat biopsy to assess
bone marrow cellularity of > 15% will be required only for patients randomized to the
Zevalin Regimen.
10. Life expectancy of 6 months or longer.
11. Written informed consent obtained according to local guidelines.
6.2 Exclusion Criteria
1. Presence of any other malignancy or history of prior malignancy within 5 years of study
entry. Within 5 years, patients treated with curative intent for Stage I or II cancers are
eligible provided they have a life expectancy of > 5 years. The 5-year exclusion rule does
not apply to-non melanoma skin tumors and in situ cervical cancer.
2. Prior radioimmunotherapy, including radiation therapy for NHL, or any other NHL
therapy.
3. Presence of central nervous system (CNS) involvement, or testicular lymphoma at first
diagnosis.
4. DLBCLas histological transformation of previously diagnosed indolent B-cell
lymphoma. Patients with De Novo Transformed DLBCL, defined as DLBCL on lymph
node biopsy and a “discordant marrow” with small cells at initial diagnosis, are eligible.
5. Known seropositivity for hepatitis C virus (HCV) or hepatitis B surface antigen (HbsAg).
Patients who are positive for HbsAg but without active disease (Hep B PCR below the
limits of detection) and who receive adequate prophylaxis may be enrolled, but should
continue prophylaxis for at least 6 months after the last dose of rituximab or Zevalin.
6. Known history of HIV infection.
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7. Abnormal liver function: total bilirubin > 2 × ULN unless secondary to Gilbert disease.
8. Abnormal renal function: serum creatinine > 2.0 × ULN.
9. Ongoing toxic effects of chemotherapy > grade 2 and expected to interfere with Zevalin
treatment.
10. Known hypersensitivity to murine or chimeric antibodies or proteins.
11. Colony stimulating factor therapy administered more than 8 weeks after last dose of Rchemotherapy
or within 4 weeks prior to planned administration of Zevalin.
12. Concurrent severe and/or medically uncontrolled disease (e.g. uncontrolled diabetes,
congestive heart failure, myocardial infarction within 6 months of study, unstable and
uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which
could compromise participation in the study.
13. Treatment with investigational drugs less than 4 weeks prior to randomization.
14. Major surgery less than 4 weeks prior to randomization.
15. Concurrent systemic corticosteroid use for any reason except as premedication in case of
known or suspected allergies to contrast media or as premedication for potential side
effects of rituximab treatment. Patients on a chronic dose of prednisone for a medical
condition (e.g. Asthma or autoimmune disease) less than or equal to 20mg daily, stable
for 4 weeks, are permissible.
16. Unwillingness or inability to comply with the protocol.
17. Pregnant women or women who are breastfeeding
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PMDS29 – AZA-MDS-003
Bron: Protocol_AZA-MDS-003-_1May2012
Inclusion Criteria
Subjects must satisfy the following criteria to be enrolled in the study:
1. Age = 18 years§ at the time of signing the informed consent document
2. Have a documented diagnosis of MDS according to WHO 2008 classification
(Appendix A)
3. Be RBC transfusion-dependent as defined by:
 Average transfusion requirement of = 2 units** per 28 days of RBCs confirmed for a minimum
of 84 days immediately preceding randomization
o Hemoglobin levels at the time of or within 7 days prior to administration of an RBC
transfusion must have been = 9.0 g/dL in order for the transfusion to be counted
towards RBC transfusion-dependent status. Red blood cell transfusions administered
when Hgb levels were > 9.0 g/dL and/or RBC transfusions administered for elective
surgery will not qualify as a required transfusion for the purpose of providing evidence
of RBC transfusion-dependent status
 No consecutive 42 days that are RBC-transfusion-free during the 84 days immediately
preceding randomization
4. Have thrombocytopenia as defined by two platelet counts that are = 50 x 109/L and = 21 days apart.
The second confirmatory platelet count must be obtained = 14 days prior to randomization
 If additional platelet counts were obtained during the interim period, these must also have been
= 50 x 109/L. Platelet counts > 50 x 109/L within the interim period are acceptable only if
directly associated with a platelet transfusion administered within 7 days prior to the date of the
platelet count
5. Have an ECOG performance status of 0, 1, or 2 (Appendix C)
6. Females of childbearing potential (FCBP)†† may participate, providing they meet the
following conditions:
 Agree to use at least two effective contraceptive methods (oral, injectable, or implantable
hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with
spermicide; or vasectomized partner) throughout the study, and for 3 months following the last
dose of study drug; and
 Have a negative serum or urine pregnancy test (investigator’s discretion; sensitivity of at least
25 mIU/mL) at screening; and
 Have a negative serum or urine pregnancy test (investigator’s discretion) within 72 hours prior
to starting study therapy in the treatment phase (note that the screening serum pregnancy test
can be used as the test prior to starting study therapy in the treatment phase if it is performed
within the 72-hour timeframe)
7. Male subjects with a female partner of childbearing potential must agree to the use of at least two
physician-approved contraceptive methods throughout the course of the study and should avoid
fathering a child during the course of the study and for 3 months following the last dose of study drug
8. Understand and voluntarily sign an informed consent document prior to any study related
assessments/procedures being conducted
9. Able to adhere to the study visit schedule and other protocol requirements
§ In Japan, both the subject and the subject’s legal representative must sign an informed consent document in case the age of the
subject has not reached 20 years.
** As is consistent with medical practice in Japan, 1 unit RBC referenced in this protocol is equivalent to 2 units RBC in Japan.
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Exclusion Criteria
The presence of any of the following will exclude a subject from enrollment:
1. IPSS higher-risk (INT-2 or High risk) MDS (Appendix B)
2. Secondary MDS, ie MDS that is known to have arisen as the result of chemical injury or treatment with
chemotherapy and/or radiation for other diseases
3. Hypoplastic MDS or other subtype with eligibility for treatment with immunotherapy
4. CMML, atypical chronic myeloid leukemia (CML) and unclassifiable myeloproliferative disease (MPD)
5. Prior treatment with any of the following:
 Azacitidine (any formulation), decitabine or other hypomethylating agent
 Lenalidomide
6. Prior allogeneic or autologous stem cell transplant
7. History of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis), celiac disease (ie,
sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that
would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or
predispose the subject to an increased risk of gastrointestinal toxicity
8. Thrombocytopenia secondary to other possible causes, including medication(s), congenital
disorder(s), immune disorder(s) (eg, idiopathic thrombocytopenic purpura [ITP]), or microvascular
disorder(s) (eg, disseminated intravascular coagulation, hemolytic uremic syndrome, thrombotic
thrombocytopenic purpura)
9. Use of any of the following within 28 days prior to randomization:
 cytotoxic, chemotherapeutic, targeted or investigational agents/therapies
 thrombopoiesis-stimulating agents (TSAs; eg, Romiplostim, Eltrombopag,
Interleukin-11)
 ESAs and other RBC hematopoietic growth factors (eg, Interleukin-3)
 hydroxyurea
10. Ongoing adverse events from previous treatment, regardless of the time period
11. Concurrent use of any of the following:
 iron-chelating agents, except for subjects on a stable dose for at least 8 weeks (56 days) prior
to randomization
 corticosteroid, except for subjects on a stable or decreasing dose for = 1 week prior to
randomization for medical conditions other than MDS
12. Prior history of malignancies, other than MDS, unless the subject has been free of the disease for = 3
years. However, subjects with the following history/concurrent conditions are allowed:
 Basal or squamous cell carcinoma of the skin
 Carcinoma in situ of the cervix
 Carcinoma in situ of the breast
 Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis
[TNM] clinical staging system)
13. Significant active cardiac disease within the previous 6 months, including:
 New York Heart Association (NYHA) class IV congestive heart failure (see Appendix G);
 Unstable angina or angina requiring surgical or medical intervention; and/or
 Myocardial infarction
14. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related
to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other
treatment)
15. Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence of active
Hepatitis B Virus (HBV) infection
16. Abnormal coagulation parameters (PT > 15 seconds, PTT > 40 seconds, and/or INR > 1.5)
17. Any of the following laboratory abnormalities:
 Serum AST/SGOT or ALT/SGPT > 2.5 x upper limit of normal (ULN)
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
Serum bilirubin > 1.5 x ULN. Higher levels are acceptable if these can be attributed to active
red blood cell precursor destruction within the bone marrow (ie, ineffective erythropoiesis).
Subjects are excluded if there is evidence of autoimmune hemolytic anemia manifested as a
corrected reticulocyte count of > 2% with either a positive Coombs’ test or over 50% of indirect
bilirubin
 Serum creatinine > 2.5 x ULN
18. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or
hereditary hemolytic anemia, or gastrointestinal bleeding. Iron deficiency would be determined by a
bone marrow aspirate stain for iron, the transferrin saturation (iron/total iron binding capacity [Fe/TIBC]
= 20%), or serum ferritin = 15 ng/dL
19. Known or suspected hypersensitivity to azacitidine or mannitol
20. Pregnant or lactating females
21. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the
subject from participating in the study
22. Any condition including the presence of laboratory abnormalities, which places the subject at
unacceptable risk if he/she were to participate in the study
23. Any condition that confounds the ability to interpret data from the study
†† A woman of childbearing potential is a sexually mature woman who 1) has not undergone a hysterectomy (the surgical
removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been naturally
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive
months (ie, has had menses at any time during the preceding 24 consecutive months).
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PMM25 - HOVON95 Substudie MM
Bron: ho95_pro_27may2010.pdf
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PMM27 - HOVON104 In- en exclusie criteria
Bron: HO104 pro v AM3_27112012 signed.pdf
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Vervolg exclusie criteria:
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PSCT16 - In- en exclusie criteria
Bron: PSCT16_Protocol_clean_versie1.6_12feb2013
Patient inclusion criteria
 Patients with AML, myelodysplasia (MDS), ALL, CML (accelerated or blast phase), CLL, MM or
malignant NHL, who underwent partially T cell-depleted allo-SCT

Patients positive for HLA-A2 and/or HLA-B7

Patients positive for HA-1, LRH-1 and/or ARHGDIB transplanted with corresponding MiHA-negative
donor

Patients >18 and <65 years of age

WHO performance 0-2 (see Appendix 3)

Witnessed written informed consent
Patient exclusion criteria
 Life expectancy < 3 months

Severe neurological or psychiatric disease

Progressive disease needing cytoreductive therapy

HIV positivity

Patients with acute GVHD grade 3 or 4

Patients with extensive chronic GVHD

Patients with active infections (viral, bacterial or fungal) that requires specific therapy. Acute antiinfectious therapy must have been completed within 14 days prior to study treatment

Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or
symptomatic ischemic heart disease

Severe pulmonary dysfunction

Severe renal dysfunction (serum creatinine > 3 times normal level)

Severe hepatic dysfunction (serum bilirubin or transaminases > 3 times normal level)

Patients with known allergy to shell fish
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PSCT17 - HOVON115
Bron: ho115-pro-v2-31may2012_signed.pdf
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SC26 - EORTC 65091-06093
Bron: Protocol EORTC 65091-06093 FP v1.2.pdf
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PSCT18 – XEN/TG-001
Bron: Gebaseerd op protocol versie 2.0 01092013
Inclusion criteria
• Patients suffering from acute GVHD which is staged as Grade II-IV (Appendix
1) according to the modified Glucksberg Criteria and progressing after 3 days,
or not improving after 7 days, of methylprednisolone at a dose of 2 mg/kg per
day.
• Age ≥ 18 years.
• Patients or an impartial witness (in case the patient is capable to provide
verbal consent but not capable to sign the informed consent) should have
given written informed consent.
Exclusion criteria
• Patients receiving concomitant investigational therapeutics for acute GVHD,
including investigational agents used for GVHD prophylaxis, at the time of
enrollment.
• Patients with signs or symptoms suggestive of chronic GVHD (e.g.
poikiloderma, sclerotic skin features, oral lichen type changes, nail dystrophy,
vitiligo-like depigmentation or bronchiolitis obliterans, not being caused by other
potential diagnoses such as infection, drug toxicity etc.).
• Patients requiring mechanical ventilation, requiring vasopressor support,
requiring hemodialysis, having serum creatinine > 266 μmol/l (> 3mg/dl), or
having a serum albumin level of 15 g/l or less.
• Patients having uncontrolled bacterial, viral or fungal infections, at the
discretion of the investigator, at the start of therapy.
• Patients with current signs or symptoms of active intrapulmonary disease.
• Patients with known hypersensitivity to any of the components of the study drug
(murine mAb or RTA).
• Female patients who are pregnant, breast feeding, or, if sexually active,
unwilling to use effective birth control for the duration of the study.
• Male patients who are, if sexually active, unwilling to use effective birth control
for 30 days after the last infusion.
• Patients participating in a clinical trial with another investigational medicinal
product within 30 days prior to providing informed consent.
• Patients whose decision to participate might be unduly influenced by perceived
expectation of gain or harm by participation, such as patients in detention due
to official or legal order.
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PcMPD03 – ARD12181
Bron: PcMPD03 protocol version3 dd28nov2012.pdf
YES
INCLUSIE CRITERIA

I01
I 01. Diagnosis of PMF or Post-PV MF or Post-ET MF, according to the 2008 World
Health
Organization (Appendix B) and IWG-MRT criteria (Appendix C).

I02
Subjects who previously received Ruxolitinib treatment for PMF or Post-PV MF or PostET MF or PV or ET for at least 14 days and discontinued the treatment for at least 30
days prior to study entry.

I03
Myelofibrosis classified as high-risk or intermediate-risk level 2 (IWG-MRT response
criteria IPSS assess MF score (Cervantes, et al, Blood 2009 [1]).

I04
Spleen ≥5 cm below costal margin as measured by palpation.
I 05.

I05
Male and female subjects ≥18 years of age.

I06
Signed written informed consent.
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No/Nee
EXCLUSIE CRITERIA ARD12181 studie

Eastern Cooperative Oncology Group (ECOG) PS of >2 at study entry (Appendix E).
E01
The following laboratory values within 14 days prior to the initiation of SAR302503:
• Absolute neutrophil count (ANC) <1.0 x 109/L
• Platelet count <50 x 109/L
• Serum creatinine >1.5 x upper limit of normal (ULN)
• Serum amylase and lipase >1.5 x ULN
Subjects with known active (acute or chronic) Hepatitis A, B, or C; and hepatitis B and C
carriers

E02

E03

E04

E05

E06

E07

E08

E09

E10
Splenectomy

E11
Any chemotherapy, immunomodulatory drug therapy (eg, thalidomide, interferon-alpha),
Anagrelide, immunosuppressive therapy, corticosteroids >10 mg/day prednisone or
equivalent, or growth factor treatment (eg, erythropoietin), or hormones (eg, androgens,
danazol) within 14 days prior to initiation of SAR302503; darbepoetin use within 28 days
prior to initiation of SAR302503. The only chemotherapy allowed will be hydroxyurea
within 1 day prior to initiation of SAR302503.

E12
Major surgery within past 28 days or radiation within 6 months prior to initiation of
SAR302503

E13
Concomitant treatment with or use of pharmaceutical or herbal agents known to be
moderate or severe inhibitors or inducers of CYP3A4 (Appendix D)

E14
Treatment with aspirin in doses >150 mg/day within a week

E15

E16

E17

E18
Active acute infection requiring antibiotics
Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4),
angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass
graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to
initiation of SAR302503(Appendix F)
Participation in any study of an investigational agent (drug, biologic, device) within 30
days prior to initiation of SAR302503, unless during a non-treatment phase
Pregnant or lactating female
AST or ALT ≥2.5 x ULN
Total Bilirubin:
• Exclude if ≥3.0 x ULN
• Subjects with total bilirubin between 1.5-3.0 x ULN must be excluded if the direct
bilirubin fraction is ≥25% of the total
Subjects with prior history of chronic liver disease (eg, chronic alcoholic liver disease,
autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis,
non-alcoholic steatohepatitis [NASH])
Life expectancy <6 months.
Subjects with any other prior malignancies are not eligible, except for the following:
adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or
other cancer from which subject has been disease-free for at least 5 years
Lack of willingness or ability to comply with scheduled visits, treatment plans, laboratory
assessments and other study-related procedures
Pagina 40 van 41
Lijsten studies
met in- en exclusiecriteria (juni 2014)

E19

E20

E21

E22

E23

E24
Women of childbearing potential, unless using effective contraception while on
SAR302503
Men who partner with a woman of childbearing potential, unless they agree to use
effective contraception while on SAR302503
Known human immunodeficiency virus or acquired immunodeficiency syndrome-related
illness
Any severe acute or chronic medical, neurological, or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or SAR302503
administration, may interfere with the informed consent process and/or with compliance
with the requirements of the study, or may interfere with interpretation of study results
and, in the Investigator’s opinion, would render the subject inappropriate for entry into this
study
Unable to swallow capsules
Presence of any significant gastric or other disorder that would inhibit absorption of oral
medication
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Pagina 41 van 41

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