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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


Phase 3
60 Years
N/A
Not Enrolling
Both
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

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Overall survival (OS)

Outcome Time Frame:

Up to 10 years

Safety Issue:

No

Principal Investigator

Guido Marcucci

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02805

NCT ID:

NCT00085124

Start Date:

December 2003

Completion Date:

Related Keywords:

  • 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
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Cancer and Leukemia Group BChicago, Illinois  60606