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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00039117
First received: June 6, 2002
Last updated: December 13, 2012
Last verified: December 2012
History of Changes
  Purpose

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


Condition Intervention Phase
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
 Biological: oblimersen sodium
Drug: cytarabine
Drug: daunorubicin hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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) 60 Years of Age

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD of cytarabine and daunorubicin in combination with G3139, defined as the dose level just below the dose level at which DLT is observed in 2 patients, graded according to NCI CTC version 2.0 [ Time Frame: Up to day 10 ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events, graded according to NCI CTC version 2.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    We will define the qualitative and quantitative toxicities in regard to organ specificity, time course, predictability, and reversibility.


Secondary Outcome Measures:
  • Pharmacokinetics of G3139 [ Time Frame: During induction therapy on day 1 at hour 0 and 24hours after G3139 administration; day 4 at hour 73 before cytarabine administration; day 11 at hour 0 and .5, 1, 2, 4, 6, and 8 hours ] [ Designated as safety issue: No ]
  • Level of bcl-2 in circulating and/or marrow leukemic blasts before and after initiation of treatment with G3139 [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
  • Spontaneous rate of apoptosis in leukemic blasts before and after initiation of treatment with G3139 [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
  • Incidence of therapeutic response (complete remission [CR]) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: April 2002
Estimated Primary Completion Date: January 2100 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

 Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00039117

Locations
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Guido Marcucci Ohio State University Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00039117     History of Changes
Other Study ID Numbers: NCI-2012-01409, OSU-0164, U01CA076576, CDR0000069353
Study First Received: June 6, 2002
Last Updated: December 13, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on May 16, 2013