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

Alternate Title

Oblimersen, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	60 and over	NCI	OSU-0164 NCI-4630, NCT00039117, 4630

Objectives

1. Determine the maximum tolerated dose of daunorubicin in combination with cytarabine and oblimersen in older patients with previously untreated acute myeloid leukemia.
2. Determine the qualitative and quantitative toxic effects of this regimen in these patients.
3. Determine the pharmacokinetics of oblimersen in this regimen in these patients.
4. Determine the disease-free survival and overall survival of patients treated with this regimen.
5. Assess the spontaneous rate of apoptosis in leukemic blasts in patients before and after initiation of treatment with oblimersen.
6. Determine therapeutic response (complete remission) in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed primary or secondary acute myeloid leukemia (AML)
  • More than 20% bone marrow blasts
  • Myelodysplastic syndromes (MDS) or a chronic myeloproliferative disorder antecedent to AML allowed
  • Therapy-related AML allowed
  • No acute promyelocytic leukemia

Prior/Concurrent Therapy:

Biologic therapy:

• No prior therapy for primary AML except emergency leukapheresis

Chemotherapy:

• No prior anthracyclines
• No prior chemotherapy for primary AML except hydroxyurea for hyperleukocytosis
• At least 3 months since prior chemotherapy for MDS or chronic myeloproliferative disorders antecedent to AML
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent corticosteroids as anti-emetics
• No concurrent steroids except for adrenal failure or septic shock
• No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes, tamoxifen or equivalent for breast cancer prevention or adjuvant treatment, or estrogens or progestins for gynecologic indications)

Radiotherapy:

• No prior radiotherapy for primary AML except cranial radiotherapy for CNS leukostasis
• No concurrent palliative radiotherapy
• No concurrent whole brain radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent investigational or commercial agents or therapies
• No concurrent cyclooxygenase-2 inhibitors

Patient Characteristics:

Age:

• 60 and over

Performance status:

• Not specified

Life expectancy:

• At least 4 weeks

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2 mg/dL
• ALT and AST no greater than 2 times upper limit of normal (unless directly attributable to AML)

Renal:

• Creatinine no greater than 2.5 mg/dL

Cardiovascular:

• Ejection fraction at least 50% by MUGA or echocardiogram
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• No allergy to any of the study medications
• No other uncontrolled concurrent illness
• No serious medical or psychiatric illness that would preclude giving informed consent
• Not pregnant or nursing
• Fertile patients must use effective contraception

Expected Enrollment

A total of 12-32 patients (6-16 per stratum) will be accrued for this study within 9 months.

Outline

This is a dose-escalation study of daunorubicin. Patients are stratified according to disease status (primary vs secondary).

• Induction therapy: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6.

  Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.




• Consolidation therapy: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course.

Cohorts of 3-6 patients receive escalating doses of daunorubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 2 months for 2 years.

Trial Contact Information

Trial Lead Organizations

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Guido Marcucci, MD, Protocol chair		Ph: 614-293-9868

Registry Information
Official Title		A Phase I Study Of G3139 (NSC # 683428) In Combination With Cytarabine And Daunorubicin In Previously Untreated Patients With Acute Myeloid Leukemia (AML) Greater Than Or Equal To 60 Years of Age
Trial Start Date		2002-04-10
Registered in ClinicalTrials.gov		NCT00039117
Date Submitted to PDQ		2002-03-29
Information Last Verified		2006-02-07
NCI Grant/Contract Number		P30-CA16058, U10-CA76576

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