Ignite Creation Date:
2024-05-05 @ 9:53 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002925
Status:
COMPLETED
Last Update Posted:
2012-11-30
First Post:
1999-11-01
Brief Title:
Combination Chemotherapy Plus PSC 833 Followed by Interleukin-2 in Treating Patients With Acute Myelogenous Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase I Study of MDR Modulation With PSC-833 NSC 648265 With a Pilot Study of Cytogenetic Risk-Adapted Consolidation Followed by a Phase II Pilot Study of Immunotherapy With RIL-2 NSC 373364 in Previously Untreated Patients With AML 60 Years
Status:
COMPLETED
Status Verified Date:
2011-03
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:
RATIONALE Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die Some cancers may become resistant to chemotherapy drugs Combining PSC 833 with chemotherapy may reduce resistance to the drugs and allow the cancer cells to be killed Interleukin-2 may stimulate a persons white blood cells to kill leukemia cells
PURPOSE Phase III trial to study the effectiveness of combination chemotherapy plus PSC 833 followed by additional chemotherapy or peripheral stem cell transplantation and interleukin-2 in treating patients with untreated acute myelogenous leukemia
PURPOSE Phase III trial to study the effectiveness of combination chemotherapy plus PSC 833 followed by additional chemotherapy or peripheral stem cell transplantation and interleukin-2 in treating patients with untreated acute myelogenous leukemia
Detailed Description:
OBJECTIVES I Determine the maximum tolerated dose MTD of daunorubicin when used in combination with etoposide cytarabine and PSC 833 ADEP and in combination with etoposide and cytarabine ADE in previously untreated patients with acute myelogenous leukemia who are less than 60 years II Determine the MTD of etoposide when used in combination with a constant dose of daunorubicin and cytarabine ADE in these patients III Determine the feasibility and toxic effects of administering postremission therapy in a risk adapted fashion such that patients with favorable cytogenetic findings receive three intensifications with high dose cytarabine HiDAC while average to poor risk patients receive HiDACetoposidefilgrastim G-CSF for consolidation therapy and stem cell mobilization followed by peripheral stem cell PBSC transplant using busulfanetoposide as the preparative regimen IV Determine the feasibility and toxic effects of the consolidation sequence of HiDACetoposideG-CSF followed by 2 courses of HiDAC in patients who would otherwise receive PBSC transplant but are unable to do so for logistical or institutional reasons V Determine the feasibility of intermittent administration of high dose subcutaneous interleukin-2 IL-2 in combination with continuous low dose subcutaneous IL-2 in patients recovering from PBSC transplant or intensive consolidation chemotherapy
OUTLINE This is a dose escalation study of daunorubicin in the induction therapy portion with a separate dose escalation study of etoposide in the same portion Patients are treated with three phases of treatment induction intensification and postremission therapy Induction therapy Patients receive cytarabine IV as a continuous infusion on days 1-7 plus daunorubicin IV over 30 minutes and etoposide IV over 2 hours on days 1-3 ADE regimen Some patients also receive PSC 833 IV as a continuous infusion on days 1-3 ADEP regimen This course may be repeated 14 days later Cohorts of 9 patients each receive escalating doses of daunorubicin until the maximum tolerated dose MTD is reached The MTD is defined as the dose at which 3 of 9 patients experience dose limiting toxicity Escalations are conducted separately for the ADE and ADEP regimens Other cohorts of 9 patients each receive escalating doses of etoposide with constant doses of daunorubicin in the ADE regimen The MTD is described in the same manner Intensification therapy Arm I patients with certain genetic characteristics in their leukemia cells Patients receive 3 additional courses of cytarabine IV over 3 hours twice a day for 3 days Courses are repeated every 28 days Arm II patients who do not have these genetic characteristics Patients undergo a peripheral blood stem cell PBSC transplant Patients first receive high dose cytarabine IV over 2 hours on days 1-4 etoposide IV as a continuous infusion on days 1-4 and filgrastim G-CSF subcutaneously beginning on day 5 until blood counts recover PBSC are then collected Approximately 4-6 weeks later patients receive oral busulfan 4 times a day on days 1-4 and etoposide IV over 4 hours on day 5 PBSC are reinfused on day 7 G-CSF is administered subcutaneously beginning on day 7 until blood cell counts recover Arm III patients who cannot undergo a PBSC transplant Patients receive cytarabine etoposide and G-CSF as in arm II then high dose cytarabine as in arm I Postremission therapy all patients Patients receive low dose interleukin-2 IL-2 by daily injection for 2 weeks On day 15 patients begin receiving intermittent high dose IL-2 three days a week Patients alternate these courses of IL-2 14 days of low dose IL-2 3 days of high dose IL-2 1 day of rest low dose IL-2 for 10 days then 3 days of high dose IL-2 then 1 day of rest This course is repeated 3 times Patients then receive another 16 day course of low dose IL-2 Patients are followed at 1 month then every 3 months for 2 years then every 6 months for 2 years then annually thereafter
PROJECTED ACCRUAL Approximately 410 patients will be accrued into this study within 36 months
OUTLINE This is a dose escalation study of daunorubicin in the induction therapy portion with a separate dose escalation study of etoposide in the same portion Patients are treated with three phases of treatment induction intensification and postremission therapy Induction therapy Patients receive cytarabine IV as a continuous infusion on days 1-7 plus daunorubicin IV over 30 minutes and etoposide IV over 2 hours on days 1-3 ADE regimen Some patients also receive PSC 833 IV as a continuous infusion on days 1-3 ADEP regimen This course may be repeated 14 days later Cohorts of 9 patients each receive escalating doses of daunorubicin until the maximum tolerated dose MTD is reached The MTD is defined as the dose at which 3 of 9 patients experience dose limiting toxicity Escalations are conducted separately for the ADE and ADEP regimens Other cohorts of 9 patients each receive escalating doses of etoposide with constant doses of daunorubicin in the ADE regimen The MTD is described in the same manner Intensification therapy Arm I patients with certain genetic characteristics in their leukemia cells Patients receive 3 additional courses of cytarabine IV over 3 hours twice a day for 3 days Courses are repeated every 28 days Arm II patients who do not have these genetic characteristics Patients undergo a peripheral blood stem cell PBSC transplant Patients first receive high dose cytarabine IV over 2 hours on days 1-4 etoposide IV as a continuous infusion on days 1-4 and filgrastim G-CSF subcutaneously beginning on day 5 until blood counts recover PBSC are then collected Approximately 4-6 weeks later patients receive oral busulfan 4 times a day on days 1-4 and etoposide IV over 4 hours on day 5 PBSC are reinfused on day 7 G-CSF is administered subcutaneously beginning on day 7 until blood cell counts recover Arm III patients who cannot undergo a PBSC transplant Patients receive cytarabine etoposide and G-CSF as in arm II then high dose cytarabine as in arm I Postremission therapy all patients Patients receive low dose interleukin-2 IL-2 by daily injection for 2 weeks On day 15 patients begin receiving intermittent high dose IL-2 three days a week Patients alternate these courses of IL-2 14 days of low dose IL-2 3 days of high dose IL-2 1 day of rest low dose IL-2 for 10 days then 3 days of high dose IL-2 then 1 day of rest This course is repeated 3 times Patients then receive another 16 day course of low dose IL-2 Patients are followed at 1 month then every 3 months for 2 years then every 6 months for 2 years then annually thereafter
PROJECTED ACCRUAL Approximately 410 patients will be accrued into this study within 36 months
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 |
|---|---|---|---|
| CLB-9621 | US NIH GrantContract | None | httpsreporternihgovquickSearchU10CA031946 |
| U10CA031946 | NIH | None | None |