NCT00763763

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (actual)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	Imatinib mesylate	imatinib 600 mg/day for 2 years
DRUG	Interferon	45 micrograms per week during 2 years
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

Timeline

• Start date: 2004-12-01
• Primary completion: 2007-10-01
• Completion: 2010-01-01
• First posted: 2008-10-01
• Last updated: 2011-10-05

Locations

1 site across 1 country: France