Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00006363
Status:
COMPLETED
Last Update Posted:
2013-06-04
First Post:
2000-10-04
Brief Title:
Combination Chemotherapy With or Without PSC 833 Peripheral Stem Cell Transplantation andor Interleukin-2 in Treating Patients With Acute Myeloid Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase III Randomized Study of Induction Chemotherapy With or Without MDR-Modulation With PSC-833 NSC 648265 IND 41121 Followed by Cytogenetic Risk-Adapted Intensification Therapy Followed by Immunotherapy With rIL-2 NSC 373364 IND 1969 vs Observation in Previously Untreated Patients With AML lt 60 Years
Status:
COMPLETED
Status Verified Date:
2013-06
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:
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die PSC 833 may increase the effectiveness of chemotherapy by making cancer cells more sensitive to the drugs Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells Interleukin-2 may stimulate a persons white blood cells to kill cancer cells This randomized phase III trial is studying giving combination chemotherapy together with PSC 833 followed by a peripheral stem cell transplant with or without interleukin-2 to see how well it works compared to combination chemotherapy alone followed by a peripheral stem cell transplant with or without interleukin-2 in treating patients with acute myeloid leukemia
Detailed Description:
PRIMARY OBJECTIVES
I To determine whether the addition of PSC-833 valspodar to induction chemotherapy improves disease-free survival and overall survival for patients with acute myeloid leukemia AML 60 years
II To determine whether post-consolidation immunotherapy with low-dose continuousintermittent high-dose bolus subcutaneous recombinant interleukin-2 rIL-2 aldesleukin improves disease-free survival and overall survival in patients with AML 60 years in first complete remission CR
SECONDARY OBJECTIVES
I To continue to evaluate the effectiveness of three courses of high-dose ARA-C HiDAC cytarabine as curative consolidation chemotherapy in patients with core binding factor CBF leukemias
II To continue to establish the use of intensive post-remission chemotherapy with PSCT or a novel intensification sequence consisting of HiDAChigh-dose etoposideG-CSF filgrastim followed by two cycles of HiDAC in patients in CR with unfavorable cytogenetics
III To correlate the rate of relapse and toxicity with busulfan pharmacokinetics when busulfan and etoposide are used prior to autologous stem cell transplantation for AML patients in first CR
OUTLINE This is a randomized multicenter study
INDUCTION THERAPY Patients are randomized to 1 of 2 treatment arms
ARM I Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1-3 Patients with 20 or greater bone marrow cellularity and greater than 5 leukemia blasts at the end of the first course receive a second course of cytarabine IV continuously on days 1-5 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1 and 2
ARM II Patients receive PSC 833 IV continuously on days 1-3 and cytarabine daunorubicin and etoposide as in arm I Patients with 20 or greater bone marrow cellularity and greater than 5 leukemia blasts at the end of the first course receive a second course of PSC 833 IV continuously on days 1 and 2 and cytarabine daunorubicin and etoposide as in arm I
INTENSIFICATION THERAPY Patients in complete remission receive intensification therapy Therapy begins no earlier than 2 weeks and no later than 4 weeks after complete remission is attained Patients are stratified according to cytogenetics favorable t821q22q22 or inv16p13q22 or t1616p13q22 vs unfavorable all other karyotypes
FAVORABLE Patients receive high-dose cytarabine HiDAC IV over 3 hours every 12 hours on days 1 3 and 5 Treatment repeats no earlier than 28 days after the prior course and no later than 14 days after hematopoietic recovery for two more courses
UNFAVORABLE Patients are further divided into two groups based on ability to receive peripheral blood stem cell transplantation PBSCT yes vs no
PBSCT GROUP Patients receive etoposide IV continuously and HiDAC IV over 2 hours every 12 hours on days 1-4 Patients also receive filgrastim G-CSF subcutaneously SC daily beginning on day 14 and continuing until peripheral blood stem cell PBSC collection is completed Patients who are not able to undergo PBSCT after HiDACetoposide continue treatment in the non-PBSCT group At least 4 weeks after HiDACetoposide recovery patients receive oral busulfan every 6 hours on days -7 to -4 and etoposide IV over 4 hours on day -3 prior to PBSCT Patients receive autologous PBSC infusion on day 0 Patients also receive G-CSF SC beginning on day 0 and continuing until hematopoietic recovery
NON-PBSCT GROUP Patients receive etoposide HiDAC and G-CSF as in the PBSCT group After hematopoietic recovery patients then receive HiDAC IV over 3 hours every 12 hours on days 1 3 and 5 Treatment repeats no earlier than 28 days after prior course and no later than 14 days after hematopoietic recovery for one more course
IMMUNOTHERAPY Patients are again randomized to 1 of 2 treatment arms
ARM I Patients begin therapy no later than 120 days after the first day of the last course of HiDAC treatment OR day 0 of PBSCT Patients receive low-dose interleukin-2 IL-2 SC on days 1-14 19-28 33-42 47-56 61-70 and 75-90 In addition patients receive high-dose IL-2 SC on days 15-17 29-31 43-45 57-59 and 71-73
ARM II Patients are observed and receive no further therapy
Patients are followed at 1 month every 2 months for 2 years every 6 months for 2 years and then annually for 6 years
PROJECTED ACCRUAL A total of 720 patients will be accrued for this study within 4 years
I To determine whether the addition of PSC-833 valspodar to induction chemotherapy improves disease-free survival and overall survival for patients with acute myeloid leukemia AML 60 years
II To determine whether post-consolidation immunotherapy with low-dose continuousintermittent high-dose bolus subcutaneous recombinant interleukin-2 rIL-2 aldesleukin improves disease-free survival and overall survival in patients with AML 60 years in first complete remission CR
SECONDARY OBJECTIVES
I To continue to evaluate the effectiveness of three courses of high-dose ARA-C HiDAC cytarabine as curative consolidation chemotherapy in patients with core binding factor CBF leukemias
II To continue to establish the use of intensive post-remission chemotherapy with PSCT or a novel intensification sequence consisting of HiDAChigh-dose etoposideG-CSF filgrastim followed by two cycles of HiDAC in patients in CR with unfavorable cytogenetics
III To correlate the rate of relapse and toxicity with busulfan pharmacokinetics when busulfan and etoposide are used prior to autologous stem cell transplantation for AML patients in first CR
OUTLINE This is a randomized multicenter study
INDUCTION THERAPY Patients are randomized to 1 of 2 treatment arms
ARM I Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1-3 Patients with 20 or greater bone marrow cellularity and greater than 5 leukemia blasts at the end of the first course receive a second course of cytarabine IV continuously on days 1-5 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1 and 2
ARM II Patients receive PSC 833 IV continuously on days 1-3 and cytarabine daunorubicin and etoposide as in arm I Patients with 20 or greater bone marrow cellularity and greater than 5 leukemia blasts at the end of the first course receive a second course of PSC 833 IV continuously on days 1 and 2 and cytarabine daunorubicin and etoposide as in arm I
INTENSIFICATION THERAPY Patients in complete remission receive intensification therapy Therapy begins no earlier than 2 weeks and no later than 4 weeks after complete remission is attained Patients are stratified according to cytogenetics favorable t821q22q22 or inv16p13q22 or t1616p13q22 vs unfavorable all other karyotypes
FAVORABLE Patients receive high-dose cytarabine HiDAC IV over 3 hours every 12 hours on days 1 3 and 5 Treatment repeats no earlier than 28 days after the prior course and no later than 14 days after hematopoietic recovery for two more courses
UNFAVORABLE Patients are further divided into two groups based on ability to receive peripheral blood stem cell transplantation PBSCT yes vs no
PBSCT GROUP Patients receive etoposide IV continuously and HiDAC IV over 2 hours every 12 hours on days 1-4 Patients also receive filgrastim G-CSF subcutaneously SC daily beginning on day 14 and continuing until peripheral blood stem cell PBSC collection is completed Patients who are not able to undergo PBSCT after HiDACetoposide continue treatment in the non-PBSCT group At least 4 weeks after HiDACetoposide recovery patients receive oral busulfan every 6 hours on days -7 to -4 and etoposide IV over 4 hours on day -3 prior to PBSCT Patients receive autologous PBSC infusion on day 0 Patients also receive G-CSF SC beginning on day 0 and continuing until hematopoietic recovery
NON-PBSCT GROUP Patients receive etoposide HiDAC and G-CSF as in the PBSCT group After hematopoietic recovery patients then receive HiDAC IV over 3 hours every 12 hours on days 1 3 and 5 Treatment repeats no earlier than 28 days after prior course and no later than 14 days after hematopoietic recovery for one more course
IMMUNOTHERAPY Patients are again randomized to 1 of 2 treatment arms
ARM I Patients begin therapy no later than 120 days after the first day of the last course of HiDAC treatment OR day 0 of PBSCT Patients receive low-dose interleukin-2 IL-2 SC on days 1-14 19-28 33-42 47-56 61-70 and 75-90 In addition patients receive high-dose IL-2 SC on days 15-17 29-31 43-45 57-59 and 71-73
ARM II Patients are observed and receive no further therapy
Patients are followed at 1 month every 2 months for 2 years every 6 months for 2 years and then annually for 6 years
PROJECTED ACCRUAL A total of 720 patients will be accrued for this study within 4 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-19808 | None | None | None |