STI571 Plus Combination Chemotherapy in Treating Patients With Chronic Myelogenous Leukemia or Acute Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. STI571 may stop the growth of leukemia cells. Combining chemotherapy and STI571 may kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus STI571 in treating patients who have chronic myelogenous leukemia or acute lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of daunorubicin when combined with imatinib mesylate, vincristine, and prednisone in patients with lymphoid blastic phase chronic myelogenous leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Determine the safety of this regimen in these patients. Determine the pharmacokinetics of this regimen in these patients. Determine the frequency of hematologic and cytogenetic responses in patients treated with this regimen. Determine the duration of response of this patient population treated with this regimen. Determine the survival of patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of daunorubicin. Patients who have not previously received imatinib mesylate receive oral imatinib mesylate on days 1-35. Patients who have previously received imatinib mesylate for at least 28 days receive oral imatinib mesylate on days 22-35. All patients receive daunorubicin IV over 2-3 minutes on days 1-3, vincristine IV over 1 minute on days 1, 8, 15, and 22, and oral prednisone on days 1-28. Patients with more than 5% residual blasts in bone marrow on day 28 receive a second course in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of daunorubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the recommended phase II dose. PROJECTED ACCRUAL: A maximum of 46 patients will be accrued for this study.

Official Title
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A Phase I/II Trial of STI-571 and Chemotherapy in Lymphoid Blast Crisis of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Lymphoid Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Drug: daunorubicin hydrochloride
* Drug: imatinib mesylate
* Drug: prednisone
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: One of the following diagnoses: Chronic myelogenous leukemia in lymphoid blast crisis Acute lymphoblastic leukemia (ALL) that is in first relapse or failed induction No more than 1 prior course of induction chemotherapy Philadelphia chromosome-positive (Ph+) by cytogenetic analysis OR bcr/abl translocation by fluorescent in situ hybridization At least 30% blasts in bone marrow Ineligible for or refused allogeneic stem cell transplantation Not previously treated with imatinib mesylate OR currently receiving imatinib mesylate with stable disease on 2 bone marrow biopsies at least 2 weeks apart PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 3 times upper limit of normal (ULN) ALT and AST less than 3 times ULN Renal: Creatinine less than 2 times ULN Cardiovascular: No New York Heart Association class III or IV cardiac disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception during and for at least 2 weeks after study for female patients and at least 3 months after study for male patients PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior allogeneic bone marrow or peripheral blood stem cell transplantation At least 48 hours since prior interferon alfa Chemotherapy: See Disease Characteristics At least 24 hours since prior hydroxyurea At least 6 weeks since prior busulfan Concurrent hydroxyurea or anagrelide for severe leukocytosis or thrombocytosis allowed Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: No prior therapy for blast crisis except hydroxyurea No prior salvage or reinduction therapy for Ph+ ALL At least 4 weeks since other prior investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: daunorubicin hydrochloride|nan|
|Drug: imatinib mesylate|nan|
|Drug: prednisone|nan|
|Drug: vincristine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia