Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed Under 60 NCI MDA-2004-0342 NCI-6484, 6484, NCT00096148

Objectives

Primary

1. Compare the activity of idarubicin and cytarabine with or without bevacizumab in patients with newly diagnosed acute myeloid leukemia.
2. 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

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

Entry 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)

   [Note: *Enrollment without cytogenetic information is allowed for patients who require immediate therapy (e.g. patients with WBC > 50,000/mm³ or organ dysfunction thought to be due to blast infiltration of tissues)]




• No history or clinical evidence of primary brain tumors or brain metastasis

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

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)

Expected Enrollment

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

Outcomes

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

Safety of idarubicin+cytarabine+bevacizumab by AdEERS, CBC and chem. (during remission induction & consolidation every 4-7 days, and during maint. tx prior to bevacizumab dose), monthly for 6-12 mo. then every 3 mo. for 2 yrs after study complet.

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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Srdan Verstovsek, MD, Principal investigator		Ph: 713-792-7305; 800-392-1611 Email: sverstov@mdanderson.org

Registry Information
Official Title		Randomized Phase II Trial of Idarubicin + Ara-C +/- Bevacizumab in Patients Age < 60 with Untreated Acute Myeloid Leukemia
Trial Start Date		2004-10-04
Registered in ClinicalTrials.gov		NCT00096148
Date Submitted to PDQ		2004-09-09
Information Last Verified		2006-11-01
NCI Grant/Contract Number		CM17003, CA16672

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