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

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.

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.

Eligibility Criteria:
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