Rebeccamycin Analog in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

OBJECTIVES:

I. Determine the maximum tolerated dose and dose-limiting toxicity of rebeccamycin analogue (XL119) in patients with relapsed or refractory acute myeloid leukemia, myelodysplastic syndromes, acute lymphoblastic leukemia, or chronic myelogenous leukemia in blastic phase.

OUTLINE: This is a dose-escalation study.

Patients receive rebeccamycin analogue (XL119) IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 1 additional course beyond CR. Patients achieving a partial response (PR) or hematologic improvement (HI) receive 2 additional courses beyond PR or HI. Cohorts of 3-6 patients receive escalating doses of XL119 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Inclusion criteria

• Diagnosis of 1 of the following:

• Acute myeloid leukemia
• Myelodysplastic syndromes, including 1 of the following:

• Refractory anemia with excess blasts (RAEB)
• RAEB in transformation
• Chronic myelomonocytic leukemia in transformation with ≥ 10% peripheral blood or bone marrow blasts
• Acute lymphoblastic leukemia
• Chronic myelogenous leukemia in blastic phase
• Relapsed or refractory disease, defined as 1 of the following:

• Failed to achieve a complete response (CR) to a standard induction regimen
• Relapsed after achieving a CR
• Failed last cytotoxic regimen before study entry
• No alternate, potentially curative option available
• No known CNS disease
• Performance status - ECOG 0-2
• SGOT and SGPT normal
• Bilirubin normal
• Creatinine normal
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV-positive patients with normal CD4 count and without AIDS-defining disease allowed
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to rebeccamycin analogue (XL119)
• No concurrent uncontrolled illness
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance
• No prior allogeneic stem cell transplantation
• No concurrent prophylactic hematopoietic colony-stimulating factors (CSF)
• No epoetin alfa or hematopoietic CSF during course 1 of study therapy
• More than 7 days since prior cytotoxic chemotherapy except for hydroxyurea
• More than 7 days since prior radiotherapy
• Recovered from all prior therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents or therapies
• No other concurrent antileukemic agents or therapies
• No other concurrent investigational agents or therapies
• No other concurrent cytotoxic agents