Ignite Creation Date:
2024-05-05 @ 12:00 PM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00201240
Status:
COMPLETED
Last Update Posted:
2021-11-01
First Post:
2005-09-16
Brief Title:
Acute Myeloid Leukemia T Cell Depletion to Improve Transplants in Adults With Acute Myeloid Leukemia BMT CTN 0303
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
A Phase 2 Single Arm Trial of HLA-Matched Transplants CD34 Enriched T-Cell Depleted Peripheral Blood Stem Cells Isolated by CliniMACS System in the Treatment of Patients With AML in 1st or 2nd Morphologic Complete Remission BMTCTN0303
Status:
COMPLETED
Status Verified Date:
2017-08
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 study is a single arm Phase II multicenter trial It is designed to determine whether the anticipated endpoints for a T cell depleted transplant arm of a planned prospective randomized trial comparing T cell depleted and unmodified hematopoietic allografts are likely to be achieved in a multicenter study conducted by the Blood and Marrow Transplant Clinical Trials Network BMT CTN or Network The study population is patients with acute myeloid leukemia AML in first or second morphologic complete remission The enrollment is 45 patients
Based on published results of unmodified transplants from HLA-matched siblings applied to patients with AML in first or second morphologic complete remission a significant improvement in results with a graft modified as specified in this protocol would be expected if disease-free survival DFS at 6 months was greater than 75 the true incidence of transplant-related mortality at 1 year was less than 30 and the DFS rate at 2 years was greater 70 for patients transplanted in first remission and less than 60 for patients transplanted in second remission Additional secondary endpoints include the following graft failure rate and incidences of acute grade II-IV and chronic graft-versus-host disease GVHD Additionally the trial will have target specific doses of CD34 progenitors and CD3 T cells to be obtained following fractionation with the CliniMACS system Based on the results of this trial a Phase III trial comparing T cell depleted peripheral blood stem cell transplants PBSCT with unmanipulated bone marrow or unmanipulated PBSCT will be designed
Based on published results of unmodified transplants from HLA-matched siblings applied to patients with AML in first or second morphologic complete remission a significant improvement in results with a graft modified as specified in this protocol would be expected if disease-free survival DFS at 6 months was greater than 75 the true incidence of transplant-related mortality at 1 year was less than 30 and the DFS rate at 2 years was greater 70 for patients transplanted in first remission and less than 60 for patients transplanted in second remission Additional secondary endpoints include the following graft failure rate and incidences of acute grade II-IV and chronic graft-versus-host disease GVHD Additionally the trial will have target specific doses of CD34 progenitors and CD3 T cells to be obtained following fractionation with the CliniMACS system Based on the results of this trial a Phase III trial comparing T cell depleted peripheral blood stem cell transplants PBSCT with unmanipulated bone marrow or unmanipulated PBSCT will be designed
Detailed Description:
BACKGROUND
Allogeneic hematopoietic cell transplantation is an accepted therapy for AML Transplants of unmodified HLA-matched related bone marrow or peripheral blood stem cells following conditioning with total body irradiation TBI and cyclophosphamide or VP-16 or busulfan and cyclophosphamide have led to sustained DFS rates of 45-60 for adults transplanted in first complete remission CR1 and 40-53 for patients transplanted in second complete remission CR2 In several single center and multicenter cooperative group prospective trials comparing HLA-matched allogeneic transplants to chemotherapy in the treatment of AML in CR1 DFS rates for the transplant arm were almost invariably superior however these advantages were statistically significant in only a minority of the cooperative group studies conducted In each study the risk of relapse was significantly lower for patients receiving allogeneic transplants However this advantage was counterbalanced by transplant-related mortality principally reflecting infections complicating GVHD and its treatment
DESIGN NARRATIVE
Despite increased risks of infection development of effective T cell depletion TCD techniques for prevention of GVHD and tolerable modifications of regimens for pre-transplant cytoreduction that secure consistent engraftment offer the potential for significant decreases in transplant-related mortality Furthermore the use of TCD transplants in the treatment of patients with AML is not associated with substantial increases in the incidence of relapse Several single center trials indicate highly encouraging long-term results particularly for patients with AML in CR1 or CR2 Although the number of cases in each single center series is limited the consistency of the results suggests that the use of an effective technique for TCD together with an adequate cytoreductive regimen might yield transplant results superior to those achieved with unmodified grafts
Allogeneic hematopoietic cell transplantation is an accepted therapy for AML Transplants of unmodified HLA-matched related bone marrow or peripheral blood stem cells following conditioning with total body irradiation TBI and cyclophosphamide or VP-16 or busulfan and cyclophosphamide have led to sustained DFS rates of 45-60 for adults transplanted in first complete remission CR1 and 40-53 for patients transplanted in second complete remission CR2 In several single center and multicenter cooperative group prospective trials comparing HLA-matched allogeneic transplants to chemotherapy in the treatment of AML in CR1 DFS rates for the transplant arm were almost invariably superior however these advantages were statistically significant in only a minority of the cooperative group studies conducted In each study the risk of relapse was significantly lower for patients receiving allogeneic transplants However this advantage was counterbalanced by transplant-related mortality principally reflecting infections complicating GVHD and its treatment
DESIGN NARRATIVE
Despite increased risks of infection development of effective T cell depletion TCD techniques for prevention of GVHD and tolerable modifications of regimens for pre-transplant cytoreduction that secure consistent engraftment offer the potential for significant decreases in transplant-related mortality Furthermore the use of TCD transplants in the treatment of patients with AML is not associated with substantial increases in the incidence of relapse Several single center trials indicate highly encouraging long-term results particularly for patients with AML in CR1 or CR2 Although the number of cases in each single center series is limited the consistency of the results suggests that the use of an effective technique for TCD together with an adequate cytoreductive regimen might yield transplant results superior to those achieved with unmodified grafts
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 |
|---|---|---|---|
| 284 | OTHER | NHLBI | httpsreporternihgovquickSearchU01HL069348 |
| U01HL069254 | NIH | None | None |
| U01HL069249 | NIH | None | None |
| U01HL069278 | NIH | None | None |
| U01HL069294 | NIH | None | None |
| U01HL069315 | NIH | None | None |
| U01HL069348 | NIH | None | None |