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

Brief Title

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

Official Title

A Phase III Study of Daunorubicin and Cytarabine +/- G3139 (Genasense, Oblimersen Sodium, NSC #683428, IND #58842), a BCL2 Antisense Oligodeoxynucleotide, in Previously Untreated Patients With Acute Myeloid Leukemia (AML) > / = 60 Years

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.
    

Detailed Description

      OBJECTIVES: Primary

      I. Compare outcome, in terms of overall survival, disease-free survival, event-free survival,
      and complete response rate, in older patients with previously untreated acute myeloid
      leukemia treated with daunorubicin and cytarabine with or without oblimersen.

      Secondary I. Determine the significance of expression of select Bcl-2 family member proteins
      known to be modulated by oblimersen (e.g., Bcl-2) or which potentially mediate resistance to
      oblimersen (e.g., Bcl-XL or Mcl-1) in predicting clinical outcomes in patients treated with
      these regimens.

      II. Correlate clinical outcomes with serial changes in levels of mRNA and protein expression
      of Bcl-2, its pro-apoptotic binding partner Bax, and other anti-apoptotic Bax-binding
      proteins (e.g., Bcl-XL or Mcl-1) in patients treated with these regimens.

      III. Determine the effect of pre-treatment characteristics (e.g., morphology, cytogenetics,
      molecular features, expression of multidrug resistance molecules, functional assays of drug
      efflux, prior myelodysplastic syndromes, age, and white blood cells) on toxicity of these
      regimens and outcomes in these patients.

      OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment
      arms.

      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 complete remission (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.

      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.

      In both arms, treatment continues in the absence of disease progression, unacceptable
      toxicity, failure to achieve CR after 2 courses of remission induction therapy, the presence
      of leukemic cells in the cerebrospinal fluid, leukemic regrowth, or relapse during
      consolidation therapy.

      Patients are followed every 2 months for 2 years, every 3 months for 2 years, and then
      annually for 10 years.

      PROJECTED ACCRUAL: A total of 500 patients (250 per treatment arm) will be accrued for this
      study within 4.2 years.
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Overall survival (OS)

Condition

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Intervention

oblimersen sodium

Study Arms / Comparison Groups

 Arm I

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

500

Start Date

December 2003

Primary Completion Date

June 2007

Eligibility 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
      

Gender

All

Ages

60 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Guido Marcucci, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00085124

Organization ID

NCI-2012-02805

Secondary IDs

CALGB-10201

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Guido Marcucci, Principal Investigator, Cancer and Leukemia Group B

Verification Date

June 2013