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

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

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

Study Overview

• Status: Terminated
• Conditions: Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blastic Phase Chronic Myelogenous Leukemia
• Intervention / Treatment: Biological: bevacizumab; Drug: cytarabine; Drug: idarubicin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Avastin; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; rhuMAb VEGF; Drug: cytarabine; Given SC; Other Names: Cytosar-U; cytosine arabinoside; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Drug: idarubicin; Given IV; Other Names: IDA; 4-demethoxydaunorubicin; 4-DMDR; DMDR

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: July 1, 2001
• Primary Completion (Actual): September 1, 2004

Study Registration Dates

• First Submitted: September 13, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 23, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Neoplastic Processes; Cell Transformation, Neoplastic; Carcinogenesis; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Antibodies; Immunoglobulins; Bevacizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cytarabine; Idarubicin
• Other Study ID Numbers: NCI-2012-02405; N01CM17003 (U.S. NIH Grant/Contract); ID00-323; CDR0000068876 (Registry Identifier: PDQ (Physician Data Query))