Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

January 23, 2013 updated by: National Cancer Institute (NCI)

Randomized Phase II Trial of Idarubicin + Ara-C +/- Bevacizumab in Patients Age < 60 With Untreated Acute Myeloid Leukemia

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. Bevacizumab may stop the growth of cancer by stopping blood flow to the leukemic cells in the bone marrow. Giving idarubicin and cytarabine with bevacizumab may kill more cancer cells. It is not yet know whether giving idarubicin together with cytarabine is more effective with or without bevacizumab in treating acute myeloid leukemia. This randomized phase II trial is studying how well giving idarubicin and cytarabine together with bevacizumab works compared to idarubicin and cytarabine alone in treating patients with newly diagnosed acute myeloid leukemia

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Compare the activity of idarubicin and cytarabine with or without bevacizumab in patients with newly diagnosed acute myeloid leukemia.

II. Compare the proportion of patients who survive and remain in first complete remission (CR) one year from achieving CR after treatment with these regimens.

SECONDARY OBJECTIVES:

I. Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (< 45 vs 45 to 59), cytogenetics (normal vs -5/-7 vs other), flt 3 status (normal vs mutated), and type of acute myeloid leukemia (AML) (de novo vs secondary [arising after cytotoxic therapy or after an antecedent hematologic disorder, defined as a documented abnormality in blood count for >= 3 months before diagnosis of AML]. Patients who require treatment before cytogenetics or flt 3 status is known (e.g., patients with WBC > 50,000 OR with organ dysfunction thought to be due to blast infiltration) are stratified only according to age and type of AML. Induction therapy: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive idarubicin IV over 1 hour on days 1-3 and cytarabine IV continuously over 24 hours on days 1-4.

Arm II: Patients receive idarubicin and cytarabine as in arm I. Patients also receive bevacizumab* IV over 30-90 minutes on day 1. Patients who do not achieve complete remission (CR) after the first induction course may receive a second induction course approximately 28 days* later. Patients who do not achieve CR after 2 courses are removed from the study.

NOTE: *Patients in arm II receive bevacizumab, independently of chemotherapy administration schedule, once every 21 days for 1 year from CR date.

Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.

Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.

Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.

Course 3: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-2. After completion of the 4 post-CR chemotherapy courses, patients in arm I induction therapy do not receive further therapy. Patients in arm II induction therapy continue to receive bevacizumab as described above.After completion of study treatment, patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 60-120 patients (30-60 per treatment arm) will be accrued for this study within 12-30 months.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 59 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Newly diagnosed acute myeloid leukemia (AML)

    • No acute promyelocytic leukemia

    • None of the following cytogenetic abnormalities*:

      • t(8;21)
      • t(16;16)
      • inv(16)
  • No history or clinical evidence of primary brain tumors or brain metastasis
  • Performance status - ECOG 0-2
  • No bleeding diathesis or coagulopathy (unless related to AML)
  • Bilirubin ≤ 2.0 times upper limit of normal (ULN)
  • ALT ≤ 2.5 times ULN
  • Creatinine ≤ 2.0 times ULN
  • No proteinuria
  • No more than 1 g of protein on 24-hour urine collection
  • LVEF ≥ 50%
  • No uncontrolled hypertension
  • No New York Heart Association class II-IV congestive heart failure
  • No serious cardiac arrhythmia requiring medication
  • No peripheral vascular disease ≥ grade II
  • No stroke within the past 6 months

  • No arterial thromboembolic event within the past 6 months, including any of the following:

    • Transient ischemic attack
    • Cerebrovascular accident
    • Myocardial infarction
    • Unstable angina
  • No other clinically significant cardiovascular disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 3-4 months after study participation
  • No serious or non-healing wound ulcer or bone fracture
  • No uncontrolled infection
  • No significant traumatic injury within the past 28 days
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No history or clinical evidence of CNS disease (e.g., seizures not controlled with standard medical therapy)

  • Prior or concurrent transfusions or hematopoietic growth factors for AML allowed

    • No concurrent prophylactic hematopoietic colony-stimulating factors
  • Prior or concurrent hydroxyurea for AML allowed
  • More than 28 days since prior major surgery or open biopsy
  • No concurrent major surgery
  • No other prior therapy for AML

  • No concurrent full-dose anticoagulation therapy

    • Concurrent prophylactic anticoagulation (e.g. low-dose warfarin to maintain patency of permanent indwelling IV catheters) allowed provided INR < 1.5
  • No other concurrent anticancer therapies
  • No other concurrent investigational cytotoxic agents

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (idarubicin, cytarabine)

Arm I: Patients receive idarubicin IV over 1 hour on days 1-3 and cytarabine IV continuously over 24 hours on days 1-4.

Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.

Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.

Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.
Other: laboratory biomarker analysis
Correlative studies
Drug: cytarabine
Given IV
Other Names:
  • Cytosar-U
  • cytosine arabinoside
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
Drug: idarubicin
Given IV
Other Names:
  • IDA
  • 4-demethoxydaunorubicin
  • 4-DMDR
  • DMDR
Experimental: Arm II (idarubicin, cytarabine, bevacizumab)

Patients receive idarubicin and cytarabine as in arm I. Patients also receive bevacizumab* IV over 30-90 minutes on day 1. Patients who do not achieve complete remission (CR) after the first induction course may receive a second induction course approximately 28 days* later. Patients who do not achieve CR after 2 courses are removed from the study.

NOTE: *Patients in arm II receive bevacizumab, independently of chemotherapy administration schedule, once every 21 days for 1 year from CR date.

Post-CR therapy: All patients receive 4 post-CR chemotherapy courses approximately every 28 days in the absence of disease progression or unacceptable toxicity.

Course 1: Patients receive cytarabine IV continuously over 24 hours on days 1-5.

Course 2 and 4: Patients receive idarubicin IV over 1 hour and cytarabine IV continuously over 24 hours on days 1-4.
Other: laboratory biomarker analysis
Correlative studies
Biological: bevacizumab
Given IV
Other Names:
  • Avastin
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • rhuMAb VEGF
Drug: cytarabine
Given IV
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
Measure Description
Time Frame
Proportion of patients who remain alive in the first complete remission (CR) 1 year from achievement of CR assessed every 3 weeks for 1 year
Time Frame: 13 months from registration
Fisher's exact test will be used to compare the proportion of patients alive in CR 13 months from registration date. The test has approximately 89% power to detect an absolute increase of 20% in this proportion, testing at the one-sided 0.15 significance level.
13 months from registration

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety of idarubicin+cytarabine+bevacizumab by AdEERS, CBC and chem.
Time Frame: Up to 2 years after study completion
Up to 2 years after study completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Primary Completion (Actual)

November 1, 2006

Study Registration Dates

First Submitted

November 9, 2004

First Submitted That Met QC Criteria

November 8, 2004

First Posted (Estimate)

November 9, 2004

Study Record Updates

Last Update Posted (Estimate)

January 24, 2013

Last Update Submitted That Met QC Criteria

January 23, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02627
  • N01CM62204 (U.S. NIH Grant/Contract)
  • N01CM62202 (U.S. NIH Grant/Contract)
  • MDA-2004-0342
  • CDR0000391189 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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