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

Leukemia, Lymphocytic, Acute Clinical Trial

— AFR07  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00763763
• Other study ID #: P030425
• Status: Completed
• Phase: Phase 2
• First received: July 25, 2008
• Last updated: October 4, 2011
• Start date: December 2004
• Est. completion date: January 2010

Study information

• Verified date: October 2011
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: January 2010
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blast Crisis
• Leukemia
• Leukemia, Lymphocytic, Acute
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Imatinib mesylate
imatinib 600 mg/day for 2 years
• Interferon
45 micrograms per week during 2 years
• Vincristine
2 mg IV injection repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation
• Dexamethasone
40 mg PO repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation

Locations

Country	Name	City	State
France	Service Clinique des Maladies du Sang	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the rate of hematological response induced by Gleevec™ combined with vincristine and dexamethasone		After 35 days or 56 days of induction	No