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

NCT ID: NCT00763763

Last Updated: 2011-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2010-01-31

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

Conditions

Leukemia, Lymphocytic, Acute; Philadelphia Chromosome; Blast Crisis; Leukemia, Myeloid, Chronic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

imatinib in combination with chemotherapy by vincristin and dexamethasone

Group Type: EXPERIMENTAL

Imatinib mesylate

Intervention Type: DRUG

imatinib 600 mg/day for 2 years

Interferon

Intervention Type: DRUG

45 micrograms per week during 2 years

Vincristine

Intervention Type: DRUG

2 mg IV injection repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation

Dexamethasone

Intervention Type: DRUG

40 mg PO repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation

Interventions

Imatinib mesylate

imatinib 600 mg/day for 2 years

Intervention Type: DRUG

Interferon

45 micrograms per week during 2 years

Intervention Type: DRUG

Vincristine

2 mg IV injection repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation

Intervention Type: DRUG

Dexamethasone

40 mg PO repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation

Intervention Type: DRUG

Other Intervention Names

Interferon, Pegasys; Pegasys

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe ROUSSELOT, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Service Clinique des Maladies du Sang

Paris, Paris, France

Countries

France

Other Identifiers

P030425

Identifier Type: -

Identifier Source: org_study_id