RATIONALE: 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.

PURPOSE: 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.

Condition	Treatment or Intervention	Phase
adult acute erythroid leukemia adult acute monoblastic and acute monocytic leukemia adult acute myeloid leukemia childhood acute monocytic leukemia childhood acute myeloid leukemia and other myeloid malignancies secondary acute myeloid leukemia	Drug: bevacizumab  Drug: cytarabine  Drug: idarubicin  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

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

• Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized 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.

• 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.

• 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.

Patients are followed monthly for 6 months and then 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.

Ages Eligible for Study:  up to  59 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS: Age

• Under 60

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• No bleeding diathesis or coagulopathy (unless related to AML)

Hepatic

• Bilirubin ≤ 2.0 times upper limit of normal (ULN)
• ALT ≤ 2.5 times ULN

Renal

• Creatinine ≤ 2.0 times ULN
• No proteinuria OR
• No more than 1 g of protein on 24-hour urine collection

Cardiovascular

• 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

Other

• 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 CONCURRENT THERAPY: Biologic therapy

• Prior or concurrent transfusions or hematopoietic growth factors for AML allowed
• No concurrent prophylactic hematopoietic colony-stimulating factors

Chemotherapy

• Prior or concurrent hydroxyurea for AML allowed

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• More than 28 days since prior major surgery or open biopsy
• No concurrent major surgery

Other

• 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

Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009-1402,  United States; Recruiting

Study chairs or principal investigators

Srdan Verstovsek, MD,  Principal Investigator,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000391189; MDA-2004-0342; NCI-6484; NCT00096148
Record last reviewed:  November 2004
Last Updated:  February 24, 2005
Record first received:  November 9, 2004
ClinicalTrials.gov Identifier:  NCT00096148
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08