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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00023920

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Blastic Phase Chronic Myelogenous Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive	Biological: bevacizumab Drug: idarubicin Drug: cytarabine	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

Determine the anti-leukemic activity of bevacizumab, idarubicin, and cytarabine in patients with blastic phase chronic myelogenous leukemia.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2001

Actual Primary Completion Date :

Sep 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (bevacizumab, idarubicin, cytarabine) 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 Given IV Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF Drug: idarubicin Given IV Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA Drug: cytarabine Given SC Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside

Arm

Intervention/Treatment

Experimental: Treatment (bevacizumab, idarubicin, cytarabine)

Biological: bevacizumab

Given IV

Other Names:

anti-VEGF humanized monoclonal antibody

anti-VEGF monoclonal antibody

Avastin

rhuMAb VEGF

Drug: idarubicin

Given IV

Other Names:

4-demethoxydaunorubicin

4-DMDR

DMDR

IDA

Drug: cytarabine

Given SC

Other Names:

ARA-C

arabinofuranosylcytosine

arabinosylcytosine

Cytosar-U

cytosine arabinoside

Outcome Measures

Primary Outcome Measures

Improvement in response rate [Up to 3 years]
Controlled toxicity rate graded according to NCI Common Toxicity Criteria [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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