Ignite Creation Date:
2025-12-24 @ 6:58 PM
Ignite Modification Date:
2025-12-30 @ 9:23 AM
Study NCT ID:
NCT00448357
Status:
COMPLETED
Last Update Posted:
2017-07-17
First Post:
2007-03-14
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Allogeneic Hematopoietic Cell Transplantation for Patients With Busulfex-based Regimen
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
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 patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's 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 body's 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)-min/24 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)-min/24 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 ATG/Methotrexate 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 ATG/Methotrexate 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:
True
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| P30CA016086 | NIH | None | https://reporter.nih.gov/quic… | View |