Oblimersen, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia - Full Text View

Sponsor:	Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00039117

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Leukemia	Biological: oblimersen sodium Drug: cytarabine Drug: daunorubicin hydrochloride	Phase I

Study Type:	Interventional
Study Design:	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) Greater Than Or Equal To 60 Years of Age

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia

Drug Information available for: Cytarabine hydrochloride Daunorubicin Daunorubicin hydrochloride Oblimersen sodium Cytarabine

U.S. FDA Resources

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

Study Start Date:

April 2002

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of daunorubicin in combination with cytarabine and oblimersen in older patients with previously untreated acute myeloid leukemia.
Determine the qualitative and quantitative toxic effects of this regimen in these patients.
Determine the pharmacokinetics of oblimersen in this regimen in these patients.
Determine the disease-free survival and overall survival of patients treated with this regimen.
Assess the spontaneous rate of apoptosis in leukemic blasts in patients before and after initiation of treatment with oblimersen.
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.

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

Eligibility

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00039117

Locations

United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
Columbus, Ohio, United States, 43210-1240

Sponsors and Collaborators

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Guido Marcucci, MD

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier:	NCT00039117 History of Changes
Other Study ID Numbers:	CDR0000069353, OSU-0164, NCI-4630
Study First Received:	June 6, 2002
Last Updated:	February 6, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
adult acute myeloid leukemia with t(8;21)(q22;q22)

adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities

Additional relevant MeSH terms:

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 February 13, 2012