Daunorubicin Hydrochloride, Cytarabine and Oblimersen Sodium in Treating Patients With Previously Untreated Acute Myeloid Leukemia - Full Text View

Purpose

This randomized phase III trial is studying daunorubicin, cytarabine, and oblimersen to see how well they work compared to daunorubicin and cytarabine in treating older patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of daunorubicin and cytarabine by making cancer cells more sensitive to the drugs. It is not yet known whether daunorubicin and cytarabine are more effective with or without oblimersen in treating acute myeloid leukemia

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(15;17)(q22;q12) 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	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia

Drug Information available for: Cytarabine Daunorubicin Daunorubicin hydrochloride Daunorubicin citrate

U.S. FDA Resources

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

Primary Outcome Measures:

Overall survival (OS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
Complete response (CR) rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
Median disease-free survival (DFS) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Enrollment:	500
Study Start Date:	December 2003
Primary Completion Date:	June 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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 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.	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
Experimental: 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.	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

Arms

Assigned Interventions

Experimental: 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 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.

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

Experimental: 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.

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

Show Detailed Description

Eligibility

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

Criteria

Inclusion 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00085124

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

Cancer and Leukemia Group B (CALGB) Research Base

More Information

No publications provided

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00085124 History of Changes
Other Study ID Numbers:	NCI-2012-02805, CALGB 10201, U10CA031946, CDR0000367323
Study First Received:	June 10, 2004
Last Updated:	January 4, 2013
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 19, 2013