Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00085124
Status:
COMPLETED
Last Update Posted:
2024-05-30
First Post:
2004-06-10
Brief Title:
Daunorubicin Hydrochloride Cytarabine and Oblimersen Sodium in Treating Patients With Previously Untreated Acute Myeloid Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
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 gt 60 Years
Status:
COMPLETED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 eg Bcl-2 or which potentially mediate resistance to oblimersen eg 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 eg Bcl-XL or Mcl-1 in patients treated with these regimens
III Determine the effect of pre-treatment characteristics eg 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 42 years
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 eg Bcl-2 or which potentially mediate resistance to oblimersen eg 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 eg Bcl-XL or Mcl-1 in patients treated with these regimens
III Determine the effect of pre-treatment characteristics eg 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 42 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA031946 | NIH | None | httpsreporternihgovquickSearchU10CA031946 |
| CALGB-10201 | None | None | None |
| CDR367323 | None | None | None |