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

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.

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