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

Alternate Title

Daunorubicin and Cytarabine With or Without Zosuquidar Trihydrochloride in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or Refractory Anemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	Over 60	NCI	ECOG-E3999 E3999, NCT00046930

Objectives

1. Compare the overall survival and progression-free survival of elderly patients with newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts (RAEB) in transformation, or high-risk RAEB treated with daunorubicin and cytarabine with or without zosuquidar trihydrochloride.
2. Compare the complete remission rate of patients treated with these regimens.
3. Compare the toxicity of these regimens in these patients.
4. Compare the systemic exposure of daunorubicin and cytarabine in patients treated with zosuquidar trihydrochloride vs placebo.

Entry Criteria

Disease Characteristics:

• Histologically confirmed newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts (RAEB) in transformation (RAEB-T), or high-risk RAEB
  • AML with 30% myeloblasts on bone marrow aspirate or peripheral blood differential
    • Any FAB subtype except M3 (i.e., acute promyelocytic leukemia)
  • RAEB with 11-20% myeloblasts on bone marrow aspirate or peripheral blood differential, provided there are other criteria for high-risk disease
  • RAEB-T with 21-30% myeloblasts on bone marrow aspirate or peripheral blood differential



• No blastic transformation of chronic myelogenous leukemia



• Secondary AML allowed



• No CNS leukemia

Prior/Concurrent Therapy:

Biologic therapy

• No other concurrent colony-stimulating factors (e.g., epoetin alfa)

Chemotherapy

• No prior chemotherapy for AML except hydroxyurea

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age

• Over 60

Performance status

• ECOG 0-3

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin no greater than 3 mg/dL

Renal

• Creatinine less than 2 mg/dL

Cardiovascular

• Ejection fraction at least 45% by MUGA or 2-dimensional echocardiogram

Other

• No other malignancy for which patient is concurrently receiving treatment
• Not pregnant or nursing
• Fertile patients must use effective contraception

Expected Enrollment

Approximately 450 patients (225 per treatment arm) will be accrued for this study within 4.1 years.

Outline

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (60-69 years vs 70 years and over), disease (refractory anemia with excess blasts [RAEB] vs RAEB in transformation or acute myeloid leukemia [AML]), and disease type (de novo vs secondary). Patients are randomized to 1 of 2 treatment arms.

• Induction:
  • Arm I: Patients receive daunorubicin IV over 10-15 minutes and zosuquidar trihydrochloride IV over 6 hours on days 1-3. Patients also receive cytarabine IV continuously on days 1-7.
  
  
  
  • Arm II: Patients receive daunorubicin and cytarabine as in arm I. Patients also receive placebo IV over 6 hours on days 1-3.
  
  
  

  Beginning on day 12, patients who achieve aplasia receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) or IV daily until blood counts recover. Patients who have evidence of persistent AML are eligible to receive a second identical course of induction chemotherapy.




• Consolidation I (beginning within 8 weeks after documentation of complete remission [CR] or measurable remission [MR]): Patients who achieve a CR or MR receive cytarabine IV over 1 hour once or twice daily on days 1-6 and GM-CSF or G-CSF SC or IV beginning on day 7 and continuing until blood counts recover.



• Consolidation II: Patients who have maintained peripheral blood evidence of a remission receive daunorubicin, cytarabine, and zosuquidar trihydrochloride or placebo as in induction chemotherapy. Patients also receive GM-CSF or G-CSF SC or IV beginning on day 8 or after last cytarabine dose and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 2 years.

Cripe LD, Li X, Litzow M, et al.: A randomized, placebo-controlled, double blind trial of the MDR modulator, zosuquidar, during conventional induction and post-remission therapy for Pts > 60 years of age with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): ECOG 3999. [Abstract] Blood 108 (11): A-423, 2006.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Larry Cripe, MD, Protocol chair		Ph: 317-278-0757; 888-600-4822 Email: lcripe@iupui.edu
Brenda Cooper, MD, Protocol co-chair		Ph: 216-844-3213 Email: bxc12@po.cwru.edu

Registry Information
Official Title		A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride (LY335979), During Conventional Induction and Post-Remission Therapy in Patients Greater than 60 Years of Age with Newly Diagnosed Acute Myeloid Leukemia, Refractory Anemia with Excess Blasts in Transformation or High-Risk Refractory Anemia with Excess Blasts
Trial Start Date		2002-07-17
Registered in ClinicalTrials.gov		NCT00046930
Date Submitted to PDQ		2002-07-25
Information Last Verified		2005-09-23
NCI Grant/Contract Number		CA21115