IF Genasense is not working at all (for any indication) WHY NCI started large AML PIII trial, where G is in one active arm???
(In addition Aventis started PC trial:
First Published: 5/28/2004
Phase II Randomized Study of Docetaxel With or Without Oblimersen in Patients With Hormone-Refractory Adenocarcinoma of the Prostate)
First Published: 5/28/2004
Phase III Randomized Study of Daunorubicin and Cytarabine With or Without Oblimersen in Older Patients With Previously Untreated Acute Myeloid Leukemia
Objectives
Primary
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
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.
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.
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.
Projected Accrual
A total of 500 patients (250 per treatment arm) will be accrued for this study within 4.2 years.
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. |
