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

Alternate Title

Daunorubicin and Cytarabine With or Without Oblimersen in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	60 and over	NCI	CALGB-10201 NCT00085124

Objectives

Primary

1. Compare outcome, in terms of overall survival, disease-free survival, event-free survival, and complete response rate, in older patients with previously untreated acute myeloid leukemia treated with daunorubicin and cytarabine with or without oblimersen.

Secondary

1. Determine the significance of expression of select Bcl-2 family member proteins known to be modulated by oblimersen (e.g., Bcl-2) or which potentially mediate resistance to oblimersen (e.g., Bcl-XL or Mcl-1) in predicting clinical outcomes in patients treated with these regimens.
2. Correlate clinical outcomes with serial changes in levels of mRNA and protein expression of Bcl-2, its pro-apoptotic binding partner Bax, and other anti-apoptotic Bax-binding proteins (e.g., Bcl-XL or Mcl-1) in patients treated with these regimens.
3. Determine the effect of pre-treatment characteristics (e.g., morphology, cytogenetics, molecular features, expression of multidrug resistance molecules, functional assays of drug efflux, prior myelodysplastic syndromes, age, and white blood cells) on toxicity of these regimens and outcomes in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed acute myeloid leukemia



• No promyelocytic leukemia



• History of antecedent myelodysplasia allowed provided that the patient received no prior cytotoxic therapy for myelodysplastic syndromes

Prior/Concurrent Therapy:

Biologic therapy

• Prior growth factor and/or cytokine support allowed
• No concurrent routine or prophylactic myeloid growth factors

Chemotherapy

• No prior chemotherapy for leukemia or myelodysplasia except under the following conditions:
  • Emergency leukapheresis
  • Emergency treatment for hyperleukocytosis with hydroxyurea
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormones except steroids for adrenal failure or hormones for non-disease-related conditions allowed (e.g., insulin for diabetes)

Radiotherapy

• Prior cranial radiotherapy for CNS leukostasis (1 dose only) allowed
• No concurrent palliative radiotherapy

Surgery

• Not specified

Other

• Concurrent enrollment on CALGB-8461, CALGB-9665, and CALGB-9760 allowed
• No other concurrent investigational or commercial agents or therapies intended to treat the malignancy

Patient Characteristics:

Age

• 60 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Fertile patients must use effective contraception

Expected Enrollment

A total of 500 patients (250 per treatment arm) will be accrued for this study within 4.2 years.

Outcomes

Overall survival

Complete remission during remission induction therapy
Disease-free survival
Event-free survival

Outline

This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I
  • Remission induction therapy: Patients receive oblimersen IV continuously on days 1-10, cytarabine IV continuously on days 4-10, and daunorubicin IV on days 4-6.

    Patients who achieve complete remission (CR) proceed to consolidation therapy. Patients who do not achieve CR receive a second course of induction therapy.

  
  
  
  • Second remission induction therapy: Patients receive oblimersen IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.

    Patients who achieve CR proceed to consolidation therapy.

  
  
  
  • Consolidation therapy: Patients receive oblimersen IV continuously on days 1-8 and high-dose cytarabine IV over 3 hours on days 4-8. Patients with a continuing CR receive a second course of consolidation therapy.
  
  
  



• Arm II
  • Remission induction therapy: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV on days 1-3.

    Patients who achieve CR proceed to consolidation therapy. Patients who do not achieve CR receive a second course of induction therapy.

  
  
  
  • Second remission induction therapy: Patients receive cytarabine IV continuously on days 1-5 and daunorubicin IV on days 1 and 2.

    Patients who achieve CR proceed to consolidation therapy.

  
  
  
  • Consolidation therapy: Patients receive high-dose cytarabine IV over 3 hours on days 1-5. Patients with a continuing CR receive a second course of consolidation therapy.
  
  
  

In both arms, treatment continues in the absence of disease progression, unacceptable toxicity, failure to achieve CR after 2 courses of remission induction therapy, the presence of leukemic cells in the cerebrospinal fluid, leukemic regrowth, or relapse during consolidation therapy.

Patients are followed every 2 months for 2 years, every 3 months for 2 years, and then annually for 10 years.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Guido Marcucci, MD, Protocol chair		Ph: 614-293-4275

Related Information

Featured trial article

Registry Information
Official Title		A Phase III Study Of Daunorubicin And Cytarabine ± G3139 (Genesense ™, Oblimersen Sodium, NSC # 683428, IND # 58842), A BCL2 Antisense Oligodeoxynucleotide, In Previously Untreated Patients With Acute Myeloid Leukemia (AML) ≥ 60 Years
Trial Start Date		2003-12-16
Registered in ClinicalTrials.gov		NCT00085124
Date Submitted to PDQ		2004-04-19
Information Last Verified		2006-10-22
NCI Grant/Contract Number		CA31946

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