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Imatinib Mesylate With Vincristine and Dexamethasone in Acute Lymphoblastic Leukemias With BCR-ABL Positive

Phase 2
Completed
Conditions
Leukemia, Lymphocytic, Acute
Philadelphia Chromosome
Blast Crisis
Leukemia, Myeloid, Chronic
Interventions
Registration Number
NCT00763763
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

Patients not previously exposed to imatinib and with resistant or refractory Ph+ ALL, lymphoid blast crisis chronic myelogenous leukaemia (LBC CML) or with de novo Ph+ ALL and aged over 55y were eligible in the study. The DIV regimen consisted in one IV injection of vincristine 2 mg combined with 2 days of dexamethasone 40 mg PO repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation. Imatinib was administered at 800 mg per day during the induction period and at 600 mg/d continuously during consolidation. Patients in CR not eligible for HSCT were allocated to maintenance therapy consisting in weekly SC injection of Pegasys 45 µg and continuous administration of imatinib 400 mg per day for 2 years.

Detailed Description

Gleevec™ is now considered as the gold standard treatment in chronic phase chronic myeloid leukemia (CML), for patients who are not candidate for an allogenic bone marrow transplantation. However, in advanced phase CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), development of resistance to imatinib has become the central issue concerning the use of imatinib as a monotherapeutic agent. The response rate (complete hematological remission) at the dose of 600 mg/d in poor prognosis lymphoid blast phase CML and Ph+ ALL was about 20% and median time to disease progression was only 2.2 months. In VITRO studies have addressed the question of combined therapy with imatinib. A synergistic or additive activity has been demonstrated with vincristine and dexamethasone, two major drugs for the treatment of acute lymphoblastic leukemia (ALL). On going clinical studies are also testing Gleevec™ in association with daunorubicin and cytarabine (standard dose) in CML in myeloid blast phase (CST571AFR01) or with MITHOXANTROME and cytarabine (intermediate dose) as a consolidation regiment in Ph+ ALL in first CR (CSTI571AFR03). The safety of the combined therapy was excellent in the two studies. Therefore, we propose to initiate a study to assess the efficacy and the safety of Gleevec™ combined with vincristine and dexamethasone in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemias

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
55
Inclusion Criteria
  • Male or female subjects over 18 years,
  • Poor prognosis BCR-ABL transcript-positive acute lymphoblastic leukemia (refractory or relapsing Ph+ ALL, BP lymphoid CML, BP lymphoid CML in relapse)
Exclusion Criteria
  • Pregnant female,
  • Blastic involvement of the CNS,
  • Participation in an investigational agent trial within 4 weeks,
  • High dose therapy within 4 weeks,
  • Gleevec administration within 3 months,
  • Transaminases grade 3 or 4 elevation.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1Imatinib mesylateimatinib in combination with chemotherapy by vincristin and dexamethasone
1Interferonimatinib in combination with chemotherapy by vincristin and dexamethasone
1Vincristineimatinib in combination with chemotherapy by vincristin and dexamethasone
1Dexamethasoneimatinib in combination with chemotherapy by vincristin and dexamethasone
Primary Outcome Measures
NameTimeMethod
To determine the rate of hematological response induced by Gleevec™ combined with vincristine and dexamethasoneAfter 35 days or 56 days of induction
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Service Clinique des Maladies du Sang

🇫🇷

Paris, France

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