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

NCT ID: NCT00039117

Last Updated: 2015-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-04-30

Brief Summary

Phase I trial to study the effectiveness of combining oblimersen with cytarabine and daunorubicin in treating older patients who have previously untreated acute myeloid leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may help cytarabine and daunorubicin kill more cancer cells by making them more sensitive to chemotherapy.

Detailed Description

OBJECTIVES:

I. Determine the maximum tolerated dose of daunorubicin in combination with cytarabine and oblimersen in older patients with previously untreated acute myeloid leukemia.

II. Determine the qualitative and quantitative toxic effects of this regimen in these patients.

III. Determine the pharmacokinetics of oblimersen in this regimen in these patients.

IV. Determine the disease-free survival and overall survival of patients treated with this regimen.

V. Assess the spontaneous rate of apoptosis in leukemic blasts in patients before and after initiation of treatment with oblimersen.

VI. Determine therapeutic response (complete remission) in patients treated with this regimen.

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.

Conditions

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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.

Group Type: EXPERIMENTAL

oblimersen sodium

Intervention Type: BIOLOGICAL

Given IV

cytarabine

Intervention Type: DRUG

Given IV

daunorubicin hydrochloride

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

oblimersen sodium

Given IV

Intervention Type: BIOLOGICAL

cytarabine

Given IV

Intervention Type: DRUG

daunorubicin hydrochloride

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; Cerubidin; Cerubidine; daunomycin hydrochloride; daunorubicin; RP-13057; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• 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
• At least 4 weeks
• Bilirubin no greater than 2 mg/dL
• ALT and AST no greater than 2 times upper limit of normal (unless directly attributable to AML)
• Creatinine no greater than 2.5 mg/dL
• Ejection fraction at least 50% by MUGA or echocardiogram
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• 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
• No prior therapy for primary AML except emergency leukapheresis
• 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
• 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)
• No prior radiotherapy for primary AML except cranial radiotherapy for CNS leukostasis
• No concurrent palliative radiotherapy
• No concurrent whole brain radiotherapy
• No other concurrent investigational or commercial agents or therapies
• No concurrent cyclooxygenase-2 inhibitors

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guido Marcucci

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

OSU-0164

Identifier Type: -

Identifier Source: secondary_id

NCI-4630

Identifier Type: -

Identifier Source: secondary_id

CDR0000069353

Identifier Type: -

Identifier Source: secondary_id

U01CA076576

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01409

Identifier Type: -

Identifier Source: org_study_id