Ignite Creation Date:
2024-05-05 @ 5:24 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00448357
Status:
COMPLETED
Last Update Posted:
2017-07-17
First Post:
2007-03-14
Brief Title:
Allogeneic Hematopoietic Cell Transplantation for Patients With Busulfex-based Regimen
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
UNC Lineberger Comprehensive Cancer Center
Study Overview
Official Title:
Allogeneic Hematopoietic Cell Transplantation for Patients With Hematologic Disorders Who Are Undergoing Dose-Adjusted Treatment With A Maximally Intensive Busulfex-Based Therapeutic Regimen
Status:
COMPLETED
Status Verified Date:
2017-06
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:
LCCC0510
Brief Summary:
RATIONALE Giving chemotherapy such as fludarabine and busulfan before a donor peripheral stem cell transplant helps stop the growth of cancer or abnormal cells It also helps stop the patients immune system from rejecting the donors stem cells When the healthy stem cells from a donor are infused into the patient they may help the patients bone marrow make stem cells red blood cells white blood cells and platelets Sometimes the transplanted cells from a donor can make an immune response against the bodys normal cells Giving a monoclonal antibody alemtuzumab before the transplant and tacrolimus after the transplant may stop this from happening
PURPOSE The phase I portion of this trial identified the maximum tolerated dose of busulfan after treating 40 patients on a dose-escalation scheme We are now treating an additional 26 patients on the phase II portion of the trial at a Pharmacokinetic PK-directed dose of total area under curve AUC 6912 micrometer uM-min24 hours We transitioned to the Phase II portion of the study in October 2009
PURPOSE The phase I portion of this trial identified the maximum tolerated dose of busulfan after treating 40 patients on a dose-escalation scheme We are now treating an additional 26 patients on the phase II portion of the trial at a Pharmacokinetic PK-directed dose of total area under curve AUC 6912 micrometer uM-min24 hours We transitioned to the Phase II portion of the study in October 2009
Detailed Description:
OBJECTIVES
Primary
Phase I Objective To identify the maximum tolerated dose of continuous infusion IV busulfan based on blood levels derived from a test dose in conjunction with fludarabine ATG and methotrexate plus tacrolimus for GVHD prophylaxis
Phase II Objective To determine the one-year disease-free survival DFS rate at the maximum tolerated dose identified during Phase I of the trial target AUC 6912
Secondary
Determine the overall and disease-free survival of patients treated with this regimen
Determine the dose-limiting toxicities of this regimen in these patients
Determine the capacity of test dosing of busulfan that would result in the desired area under the curve concentration exposure of patients receiving a full-dose busulfan regimen
Determine the incidence of graft-vs-host disease and DNA chimerism between 1 month and 2 years post-transplantation in these patients
Compare the overall survival OS and disease-free survival DFS rates for patients treated with Campath vs patients treated with ATGMethotrexate for GVHD control
OUTLINE This is a non-randomized open-label parallel group study of busulfan Patients are stratified according to donor relationship - matched related donor MRD vs matched unrelated donor MUD
Conditioning regimen Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours once within days -15 to -10 and then IV continuously over 90 hours on days -7 to -4 Patients with a MRD also receive Methotrexate MTX on Days 1 3 and 6 Patients with a MUD receive ATG on Days -3 and -2 and MTX on Days 1 3 and 6
Phase I portion only Cohorts of 3-6 patients receive escalating doses of busulfan until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity
Allogeneic peripheral blood stem cell transplantation Patients undergo allogeneic peripheral blood stem cell transplantation on day 0 Patients then receive sargramostim GM-CSF subcutaneously beginning on day 5 and continuing until blood counts recover
Graft-vs-host disease GVHD prophylaxis Patients receive oral tacrolimus twice daily on days -1 to 180 or days -1 to 240
Donor lymphocyte infusion DLI Patients who do not achieve CR do not have GVHD and have been off immunosuppressants for at least 30 days may receive up to 3 DLIs at least 8 weeks apart after completion of tacrolimus
After the completion of study treatment patients are followed periodically for up to 5 years
Primary
Phase I Objective To identify the maximum tolerated dose of continuous infusion IV busulfan based on blood levels derived from a test dose in conjunction with fludarabine ATG and methotrexate plus tacrolimus for GVHD prophylaxis
Phase II Objective To determine the one-year disease-free survival DFS rate at the maximum tolerated dose identified during Phase I of the trial target AUC 6912
Secondary
Determine the overall and disease-free survival of patients treated with this regimen
Determine the dose-limiting toxicities of this regimen in these patients
Determine the capacity of test dosing of busulfan that would result in the desired area under the curve concentration exposure of patients receiving a full-dose busulfan regimen
Determine the incidence of graft-vs-host disease and DNA chimerism between 1 month and 2 years post-transplantation in these patients
Compare the overall survival OS and disease-free survival DFS rates for patients treated with Campath vs patients treated with ATGMethotrexate for GVHD control
OUTLINE This is a non-randomized open-label parallel group study of busulfan Patients are stratified according to donor relationship - matched related donor MRD vs matched unrelated donor MUD
Conditioning regimen Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours once within days -15 to -10 and then IV continuously over 90 hours on days -7 to -4 Patients with a MRD also receive Methotrexate MTX on Days 1 3 and 6 Patients with a MUD receive ATG on Days -3 and -2 and MTX on Days 1 3 and 6
Phase I portion only Cohorts of 3-6 patients receive escalating doses of busulfan until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity
Allogeneic peripheral blood stem cell transplantation Patients undergo allogeneic peripheral blood stem cell transplantation on day 0 Patients then receive sargramostim GM-CSF subcutaneously beginning on day 5 and continuing until blood counts recover
Graft-vs-host disease GVHD prophylaxis Patients receive oral tacrolimus twice daily on days -1 to 180 or days -1 to 240
Donor lymphocyte infusion DLI Patients who do not achieve CR do not have GVHD and have been off immunosuppressants for at least 30 days may receive up to 3 DLIs at least 8 weeks apart after completion of tacrolimus
After the completion of study treatment patients are followed periodically for up to 5 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 |
|---|---|---|---|
| P30CA016086 | NIH | None | httpsreporternihgovquickSearchP30CA016086 |