Bevacizumab, Cytarabine, and Mitoxantrone on Treating Patients With Hematologic Cancers

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as bevacizumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may be an effective treatment for hematologic cancer. PURPOSE: Phase II trial to study the effectiveness of bevacizumab combined with cytarabine and mitoxantrone in treating patients who have hematologic cancer.

Detailed Description
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OBJECTIVES: Determine the clinical effectiveness of bevacizumab, cytarabine, and mitoxantrone in patients with poor-risk hematologic malignancies. Determine the toxic effects of this regimen in these patients. Determine whether this regimen can induce cell apoptosis in these patients. Determine the effects of bevacizumab on coagulation profiles in these patients. OUTLINE: This is a multicenter study. Patients receive cytarabine IV continuously over 72 hours on days 1-3, mitoxantrone IV over 30-60 minutes on day 4, and bevacizumab IV over 90 minutes on day 8 in the absence of disease progression or unacceptable toxicity. Patients achieving partial or complete remission may receive a second course of therapy beginning approximately 30 days after the completion of the first course. Patients are followed until death. PROJECTED ACCRUAL: A total of 12-45 patients will be accrued for this study within 1-3 years.

Official Title
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A Phase II Study of the Recombinant Human Monoclonal Anti-Vascular Endothelial Growth Factor Antibody (rhuMAB VEGF) Bevacizumab (NSC #704865, IND # 7,921) Administered in Times Sequential Combination With Cytosine Arabinoside (Ara-C) and Mitoxantrone for Adults With Refractory and Relapsed Acute Myelogenous Leukemias (AMLs)

Conditions
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Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Biological: bevacizumab
* Drug: cytarabine
* Drug: mitoxantrone hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed poor-risk hematologic malignancy Relapsed or refractory acute myelogenous leukemia (AML) Primary induction failure Myelodysplasia(MDS)-related AML Secondary AML Relapsed or refractory MDS Primary induction failure Refractory anemia with excess blasts (RAEB) RAEB in transformation Chronic myelomonocytic leukemia Chronic myelogenous leukemia in blast crisis Failure of prior primary induction therapy or relapse after achieving complete remission allowed only if no more than 3 courses of prior induction/reinduction therapy were received No hyperleukocytosis (50,000 or more leukemic blasts/mm3) No active CNS leukemia PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics No disseminated intravascular coagulation Hepatic: AST/ALT no greater than 2 times normal Alkaline phosphatase no greater than 2 times normal Bilirubin no greater than 1.5 times normal Renal: Creatinine no greater than 1.5 times normal Cardiovascular: LVEF at least 45% by MUGA or echocardiogram No myocardial infarction within the past 3 months No history of severe coronary artery disease No cardiomyopathy No New York Heart Association class III or IV heart disease (congestive heart failure) Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active uncontrolled infection No history of cytarabine-related neurotoxicity No evidence of graft-versus-host disease PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior hematopoietic growth factors including epoetin alfa, filgrastim (G-CSF), and sargramostim (GM-CSF) At least 1 week since prior interleukin-3 or interleukin-11 At least 4 weeks since prior autologous stem cell transplantation At least 90 days since prior allogeneic stem cell transplantation No other concurrent immunotherapy Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy and recovered No prior cytarabine administered as a 72-hour continuous infusion followed by mitoxantrone IV over 30 minutes No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No concurrent radiotherapy Surgery: Not specified Other: At least 2 weeks since prior immunosuppressive therapy No other concurrent investigational or commercially available antitumor therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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 |
| --- |
|Biological: bevacizumab|nan|
|Drug: cytarabine|nan|
|Drug: mitoxantrone hydrochloride|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 myeloid leukemia, relapsing chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, secondary acute myeloid leukemia, previously treated myelodysplastic syndromes, childhood myelodysplastic syndromes