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

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 2

Conditions: Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blastic Phase Chronic Myelogenous Leukemia

Treatments: Drug: idarubicin; Drug: cytarabine; Biological: bevacizumab

Study type: Interventional

Funder types: NIH

Identifiers

NCT00023920

N01CM17003 (U.S. NIH Grant/Contract)

NCI-2012-02405

CDR0000068876 (Registry Identifier)

ID00-323

Details and patient eligibility

About

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

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Treatment (bevacizumab, idarubicin, cytarabine)

Experimental group

Description:

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.

Treatment:

Biological: bevacizumab

Drug: cytarabine

Drug: idarubicin