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

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Completed

CT.gov ID

NCT00015951

Collaborator

National Cancer Institute (NCI) (NIH), University of Maryland Greenebaum Cancer Center (Other)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Biological: bevacizumab Drug: cytarabine Drug: mitoxantrone hydrochloride	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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)

Study Start Date :

Apr 1, 2001

Actual Primary Completion Date :

Apr 1, 2003

Actual Study Completion Date :

Mar 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia	United States	30342-1601
2	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
3	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410