A Study of Imatinib With Reinduction Chemotherapy Using Mitoxantrone, Etoposide and Cytarabine in Patients With Relapsed/Refractory C-kit Positive (AML) Acute Myeloid Leukemia
Summary
This is a Phase I-II study evaluating the toxicity and efficacy of imatinib combined with mitoxantrone, etoposide and high-dose cytarabine reinduction therapy in relapsed and refractory AML. Patients will be treated initially at a 200 mg dose of imatinib; if tolerated, the imatinib dose will be escalated in subsequent cohorts to 300 mg and 400 mg. Once the recommended dose is determined, the remaining patients will be treated at that dose, to evaluate the antileukemic activity of the regimen. Patients achieving complete remission will receive consolidation therapy with imatinib combined with high-dose cytarabine and mitoxantrone, followed by maintenance imatinib.
Description
Induction therapy:
- Imatinib 200-400 mg p.o. daily x 10 days, Days 1-10 (see dose escalation scheme in Section 5.4 below).
- Mitoxantrone 10 mg/m2 daily x 5 days, Days 4-8.
- Etoposide 100 mg/m2 daily x 5 days, Days 4-8.
- Cytarabine 1.5 grams/m2 q12h x 4 doses, Days 9-10 (for patients aged 60 years and over, 1.0 gram/m2).
Only one induction course will be permitted. Only patients achieving CR will proceed to consolidation and maintenance.
Consolidation therapy, maximum 2 cycles (for patients achieving CR):
- Imatinib 200-400 mg p.o. daily x 8 days, Days 1-8 (see dose escalation scheme in Section 5.4 below).
- Mitoxantrone 12 mg/m2 daily x 2 days, Days 4-5.
- Cytarabine 3 grams/m2 q12h x 6 doses, Days 4,6,8. For patients aged 60 years and over, the dose will be reduced to 1.5 grams/m2.
Maintenance therapy (for patients still in CR at end of consolidation):
Imatinib 600 mg p.o. daily, until relapse or toxicity (see dose modification criteria in Section 5.6.6 below). Patients must receive at least one consolidation cycle before being permitted to proceed to maintenance therapy (see Section 5.6 for details). Maintenance therapy with imatinib will be provided for a maximum period of 1 year.
Dose escalation scheme:
Imatinib will be used during induction and consolidation at one of the following dose levels:
Level -1 100 mg daily Level 1 200 mg daily Level 2 300 mg daily Level 3 400 mg daily
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Intervention
Imatinib (Gleevec)
Location
Princess Margaret Hospital
Toronto
Ontario
Canada
M5G 2M9
Status
Completed
Source
University Health Network, Toronto
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01126814
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:13:34-0400
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Medical and Biotech [MESH] Definitions
Imatinib Mesylate
A tyrosine kinase inhibitor and ANTINEOPLASTIC AGENT that inhibits the BCR-ABL kinase created by chromosome rearrangements in CHRONIC MYELOID LEUKEMIA and ACUTE LYMPHOBLASTIC LEUKEMIA, as well as PDG-derived tyrosine kinases that are overexpressed in gastrointestinal stromal tumors.
Dasatinib
A pyrimidine and thiazole derived ANTINEOPLASTIC AGENT and PROTEIN KINASE INHIBITOR of BCR-ABL KINASE. It is used in the treatment of patients with CHRONIC MYELOID LEUKEMIA who are resistant or intolerant to IMATINIB.
Abelson Murine Leukemia Virus
A replication-defective strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) capable of transforming lymphoid cells and producing a rapidly progressing lymphoid leukemia after superinfection with FRIEND MURINE LEUKEMIA VIRUS; MOLONEY MURINE LEUKEMIA VIRUS; or RAUSCHER VIRUS.
Friend Murine Leukemia Virus
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.
Moloney Murine Leukemia Virus
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk.
