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

NCT00085124 | Completed Phase 3

• 4 other identifiers: NCI-2012-02805CALGB-10201CDR367323U10CA031946
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Overall survival (OS)

  Up to 10 years

• Complete response (CR) rate

  Up to 10 years

• Median disease-free survival (DFS)

  Up to 10 years

Study Arms (2)

Arm I

EXPERIMENTAL

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; Drug: cytarabine; Drug: daunorubicin hydrochloride; Other: laboratory biomarker analysis

Arm II

EXPERIMENTAL

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; Drug: daunorubicin hydrochloride; Other: laboratory biomarker analysis

Interventions

oblimersen sodium BIOLOGICAL

Given IV

Also known as: augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense

Arm I

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Arm I; Arm II

daunorubicin hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, daunomycin hydrochloride, daunorubicin, RP-13057

Arm I; Arm II

laboratory biomarker analysis OTHER

Correlative studies

Arm I; Arm II

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Cancer and Leukemia Group B

Chicago, Illinois, 60606, United States

Location

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

Columbus, Ohio, 43210, United States

Location

Related Publications (4)

• Seffernick AE, Mrozek K, Nicolet D, Stone RM, Eisfeld AK, Byrd JC, Archer KJ. High-dimensional genomic feature selection with the ordered stereotype logit model. Brief Bioinform. 2022 Nov 19;23(6):bbac414. doi: 10.1093/bib/bbac414.

  PMID: 36184192 DERIVED

• Walker AR, Marcucci G, Yin J, Blum W, Stock W, Kohlschmidt J, Mrozek K, Carroll AJ, Eisfeld AK, Wang ES, Jacobson S, Kolitz JE, Thakuri M, Sutamtewagul G, Vij R, Stuart RK, Byrd JC, Bloomfield CD, Stone RM, Larson RA. Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance). Blood Adv. 2021 Jul 13;5(13):2775-2787. doi: 10.1182/bloodadvances.2021004233.

  PMID: 34251414 DERIVED

• Walker CJ, Kohlschmidt J, Eisfeld AK, Mrozek K, Liyanarachchi S, Song C, Nicolet D, Blachly JS, Bill M, Papaioannou D, Oakes CC, Giacopelli B, Genutis LK, Maharry SE, Orwick S, Archer KJ, Powell BL, Kolitz JE, Uy GL, Wang ES, Carroll AJ, Stone RM, Byrd JC, de la Chapelle A, Bloomfield CD. Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia. Clin Cancer Res. 2019 Nov 1;25(21):6524-6531. doi: 10.1158/1078-0432.CCR-19-0725. Epub 2019 Aug 2.

  PMID: 31375516 DERIVED

• Yin J, LaPlant B, Uy GL, Marcucci G, Blum W, Larson RA, Stone RM, Mandrekar SJ. Evaluation of event-free survival as a robust end point in untreated acute myeloid leukemia (Alliance A151614). Blood Adv. 2019 Jun 11;3(11):1714-1721. doi: 10.1182/bloodadvances.2018026112.

  PMID: 31171508 DERIVED

Related Links

• Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

MeSH Terms

Conditions

Congenital Abnormalities

Interventions

oblimersen; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Guido Marcucci

  Cancer and Leukemia Group B

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: December 1, 2003
• Primary Completion: June 1, 2007
• Last Updated: May 30, 2024

Record last verified: 2024-05

Locations

US (2)