Bevacizumab, Idarubicin, and Cytarabine in Treating Patients With Blast Phase Chronic Myelogenous Leukemia

Study Overview
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Brief Summary
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This phase II trial is to see if combining bevacizumab with idarubicin and cytarabine works better in treating patients who have blast phase chronic myelogenous leukemia. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may be an effective treatment for blast phase chronic myelogenous leukemia

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the anti-leukemic activity of bevacizumab, idarubicin, and cytarabine in patients with blastic phase chronic myelogenous leukemia. II. Determine the toxicity profile of this regimen in these patients. III. Determine the effect of bevacizumab on angiogenesis in these patients. OUTLINE: Patients receive bevacizumab IV over 90 minutes once on day -13. Patients then receive bevacizumab IV over 90 minutes and idarubicin IV on days 1 and 15 and cytarabine subcutaneously (SC) once daily beginning on day 1. Treatment repeats every 4 weeks for a maximum of 3 courses. Patients with responding disease receive maintenance therapy comprising bevacizumab IV over 90 minutes on days 1 and 15, idarubicin IV on day 1, and cytarabine SC once daily beginning on day 1. Treatment repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase II Study of Bevacizumab (rhuMab VEGF, NSC 704865), Idarubicin and Cytarabine in Patients With Chronic Myeloid Leukemia in Blast Phase

Conditions
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Blastic Phase Chronic Myelogenous Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Intervention / Treatment
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* Biological: bevacizumab
* Drug: idarubicin
* Drug: cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Philadelphia chromosome-positive blastic phase chronic myelogenous leukemia (CML), defined by 1 of the following: At least 30% blasts in peripheral blood and/or bone marrow Presence of extramedullary disease Performance status - Zubrod 0-2 At least 8 weeks No prior coagulopathies Bilirubin no greater than 1.5 mg/dL INR less than 2 PTT no greater than 60 seconds Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min No nephrotic syndrome No uncontrolled hypertension No New York Heart Association class II-IV heart disease No prior thrombotic events LVEF ≥ 50% Not pregnant or nursing Fertile patients must use effective contraception No more than 2 prior chemotherapy regimens (no more than 1 regimen containing cytarabine) for CML in blast crisis Prior hydroxyurea allowed Prior imatinib mesylate allowed At least 10 days since prior anticoagulants No concurrent anticoagulants

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 (bevacizumab, idarubicin, cytarabine)<br>Patients receive bevacizumab IV over 90 minutes once on day -13. Patients then receive bevacizumab IV over 90 minutes and idarubicin IV on days 1 and 15 and cytarabine subcutaneously (SC) once daily beginning on day 1. Treatment repeats every 4 weeks for a maximum of 3 courses. Patients with responding disease receive maintenance therapy comprising bevacizumab IV over 90 minutes on days 1 and 15, idarubicin IV on day 1, and cytarabine SC once daily beginning on day 1. Treatment repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity. | Biological: bevacizumab<br>* Given IV<br>* Other names: rhuMAb VEGF;Drug: idarubicin<br>* Given IV<br>* Other names: IDA;Drug: cytarabine<br>* Given SC<br>* Other names: cytosine arabinoside;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in response rate |  | Up to 3 years | 
| Controlled toxicity rate graded according to NCI Common Toxicity Criteria |  | Up to 3 years |