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Blood cancer in younger adults (18-59 years)

Phase 1
Conditions
Patients with de novo acute lymphoblastic leukemia of young adults.-GRAALL-2014/B: Ph- B lineage ALL -GRAALL-2014/T et ATRIALL: T-ALL -GRAAPH-2014: ALL Ph+
MedDRA version: 20.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2014-002146-44-BE
Lead Sponsor
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
1040
Inclusion Criteria

General criteria :
1. Whose blood and bone marrow explorations have been completed before the steroids prephase
2. Aged 18 to 59 years old with not previously treated ALL (including intrathecal injections) newly diagnosed according to the WHO 2008 definition with > or = 20% bone marrow blasts
3. Without other evolving cancer (except basal cell carcinoma of the skin or in situ carcinoma of the cervix) or its treatment should be finished at least since 6 months
4. With ECOG < or = 3
5. With or without central nervous system (CNS) or testis involvement
6. Who have received or being receiving the steroid prephase
7. With efficient contraception for women of childbearing age (excluding estrogens and IUS)
8. Having signed a written informed consent
9. With health insurance coverage

GRAALL-2014/B specific:
1. With B-ALL
2. Whose karyotype shows no t(9;22) and/or the absence in molecular biology of BCR-ABL marker

GRAALL-2014/T specific:
1. With T-ALL

ATRIALL specific:
1. Included in GRAALL-2014/T
2. With HR T-ALL
3. ECOG < or = 2
4. In CR after one or two induction cures and having received the three blocks of consolidation 1
5. Without documented CNS involvement at diagnosis
6. With or without allogeneic donor

GRAAPH-2014 specific:
1. With Ph+ ALL (confirmed diagnosis of the Philadelphia chromosome defined by the reciprocal translocation of chromosomes 9 and 22, t(9;22) and/or presence of the BCR-ABL molecular maker)
2. Having received no previous treatment for this hemopathy (including IT injection)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1040
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Principal criteria:
1. Myocardial infarction within 6 months prior to inclusion in the trial, cardiomyopathy, LEVF <50% and or RF <30%
2. Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Patients not willing to ensure not to beget a child during participation in the study and at least three months thereafter
3. Not able to bear with the procedures or the frequency of visits planned in the trial
4. Unable to consent, under tutelage or curatorship, or judiciary safeguard
5. Treated with any other investigational agent or participation in another trial within 30 days prior to entering this study

GRAALL-2014/B:
1. With lymphoblastic lymphoma and bone marrow blasts <20%, Burkitt-type ALL or with antecedents of CML or other myeloproliferative neoplasm
2. HIV, HTLV-I or HCV seropositivity or chronic HBV hepatitis (HbsAg-positive)
3. With contra-indication of anthracyclines or any other general or visceral contra-indication to intensive therapy except if considered related to the ALL:
a.AST or ALT >5 x ULN
b.Total bilirubin >or= 2.5 x ULN
c.Creatinine >1.5 x ULN or creatinine clearance <50 mL/mn

GRAAL-2014/T:
1. With lymphoblastic lymphoma and bone marrow blasts <20%, Burkitt-type ALL or with antecedents of CML or other myeloproliferative neoplasm
2. Other active malignancy
3. Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Patients not willing to ensure not to beget a child during participation in the study and at least three months thereafter
4. Treated with any other investigational agent or participation in another trial within 30 days prior to entering this study
5. with severe evolving infection, or known HIV or HTLV1 seropositivity, or chronic hepatitis B (HbsAg-positive) or C
6. With contra-indication of anthracyclines or any other general or visceral contra-indication to intensive therapy except if considered related to the ALL:
a.AST or ALT >5 x ULN
b.Total bilirubin >or= 2.5 x ULN
c.Creatinine >1.5 x ULN or creatinine clearance <50 mL/mn

ATRIALL specific:
1. With ECOG status > or = 3 after consolidation 1
2. With CNS disease at diagnosis, or symptomatic CNS disease, or uncontrolled epilepsy
3. With peripheral neuropathy grade >or= 2 after consolidation 1
4. With abnormal laboratory values as defined below after consolidation 1
a. AST and/or ALT >or= 5 x ULN
b. Total bilirubin >or= 1.5 x ULN
c. Creatinine >or= 1.5 x ULN or creatinine clearance <50 ml/min
d. Serum amylase and lipase >or= 1.5 x ULN
5. With active uncontrolled infection, any other concurrent disease or medical conditionthat is deemed to interfere with the conduct of the study as judged by the investigator
6. With childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Patients not willing to ensure not to beget a child during participation in the study and at least three months thereafter
7. With known hypersensitivity to nelarabine

GRAAPH-2014:
1. Previously treated with Tyrosine Kinase Inhibitor
2. With another active malignancy
3. With general or visceral contra-indication to intensive therapy (except if considered related to the ALL):
a. ASAT and/or ALAT>or= 2.5 x ULN
b. Total bilirubin >1.5 x ULN
c. Cre

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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