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

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of rebeccamycin analog in treating patients with relapsed or refractory acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, or chronic myelogenous leukemia in blast phase. Drugs used in chemotherapy, such as rebeccamycin analog, work in different ways to stop cancer cells from dividing so they stop growing or die

Detailed Description
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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.

Official Title
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A Phase I Study Of XL119 In Patients With Relapsed Or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndromes, Acute Lymphocytic Leukemia, Or Chronic Myeloid Leukemia In Blastic-Phase

Conditions
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Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Blastic Phase Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: becatecarin
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (becatecarin)<br>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 CR receive 1 additional course beyond CR. Patients achieving a PR or HI receive 2 additional courses beyond PR or HI. Cohorts of 3-6 patients receive escalating doses of XL119 until the 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. | Drug: becatecarin<br>* Given IV<br>* Other names: XL119;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of becatecarin | Graded using the NCI CTCAE version 3.0. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | From date of first study drug administration to the date of death of the patients, assessed up to 3 years | 
| Time to progression |  | From the date of first study drug administration to the date that the patient is withdrawn because of clinical or radiographic progressive disease, or death from any cause, assessed up to 3 years | 
| Time to treatment failure |  | From the date of first study drug administration to the date of withdrawal from the study for any reason other than study closure, assessed up to 3 years | 
| Duration of response |  | From the date of first objective response to the date of progression, assessed up to 3 years | 
| Time to response |  | From the date of first study drug administration until the first objective documentation of response, assessed up to 3 years |