AFR07: Imatinib Mesylate With Vincristine and Dexamethasone in Acute Lymphoblastic Leukemias With BCR-ABL Positive

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT00763763

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Lymphocytic, Acute Philadelphia Chromosome Blast Crisis Leukemia, Myeloid, Chronic	Drug: Imatinib mesylate Drug: Interferon Drug: Vincristine Drug: Dexamethasone	Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study to Evaluate Efficacy and Safety of Glivec® in Combination With Vincristine and Dexamethasone in Patients With Lymphoid Blast Crisis CML or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in Relapse or Refractory

Study Start Date :

Dec 1, 2004

Actual Primary Completion Date :

Oct 1, 2007

Actual Study Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 imatinib in combination with chemotherapy by vincristin and dexamethasone	Drug: Imatinib mesylate imatinib 600 mg/day for 2 years Other Names: Interferon, Pegasys Drug: Interferon 45 micrograms per week during 2 years Other Names: Pegasys Drug: Vincristine 2 mg IV injection repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation Drug: Dexamethasone 40 mg PO repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation

Arm

Intervention/Treatment

Experimental: 1

imatinib in combination with chemotherapy by vincristin and dexamethasone

Drug: Imatinib mesylate

imatinib 600 mg/day for 2 years

Other Names:

Interferon, Pegasys

Drug: Interferon

45 micrograms per week during 2 years

Other Names:

Pegasys

Drug: Vincristine

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

Drug: Dexamethasone

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

Outcome Measures

Primary Outcome Measures

To determine the rate of hematological response induced by Gleevec™ combined with vincristine and dexamethasone [After 35 days or 56 days of induction]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)