Ignite Creation Date:
2024-05-05 @ 5:04 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00382109
Status:
COMPLETED
Last Update Posted:
2019-08-07
First Post:
2006-09-26
Brief Title:
Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
A Randomized Trial of Sirolimus-Based Graft Versus Host Disease Prophylaxis After Hematopoietic Stem Cell Transplantation in Relapsed Acute Lymphoblastic Leukemia
Status:
COMPLETED
Status Verified Date:
2019-06
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:
This randomized phase III trial is studying tacrolimus methotrexate and sirolimus to see how well they work compared to tacrolimus and methotrexate in preventing graft-versus-host disease in young patients who are undergoing donor stem cell transplant for intermediate-risk or high-risk acute lymphoblastic leukemia in second complete remission and high risk acute lymphoblastic leukemia in first remission Giving chemotherapy such as thiotepa and cyclophosphamide and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells It also helps stop the patients immune system from rejecting the donors stem cells The donated stem cells may replace the patients immune cells and help destroy any remaining cancer cells graft-versus-tumor effect Sometimes the transplanted cells from a donor can also make an immune response against the bodys normal cells Giving tacrolimus methotrexate and sirolimus after the transplant may stop this from happening It is not yet known whether tacrolimus and methotrexate are more effective with or without sirolimus in preventing graft-versus-host disease
Detailed Description:
PRIMARY OBJECTIVES
I Compare the post-transplant 2-year event-free survival of pediatric patients with intermediate-risk or high-risk acute lymphoblastic leukemia ALL in second complete remission or high risk ALL in first remission undergoing allogeneic hematopoietic stem cell transplantation treated with graft-versus-host disease GVHD prophylaxis comprising tacrolimus and methotrexate with or without sirolimus
SECONDARY OBJECTIVES
I Compare rates of relapses transplant-related mortality and acute and chronic GVHD in these patients
II Evaluate the relative contribution of resistance by ALL blasts to cytolytic therapy eg chemotherapyirradiation as a cause of relapse post-transplantation by correlating ALL in vivo blast resistance with in vivo sirolimus inhibition levels of the mTOR pathway in patients treated with sirolimus and altered resistance pathways in ALL blasts measured by microarray analysis
III Evaluate the relative contribution of resistance by ALL blasts to the donor immune response as a cause of relapse post-transplantation by correlating the development of donor anti-ALL T-cell response the development of acute andor chronic GVHD and the detection of altered ALL blast immunogenicity after transplant with increased minimal residual disease persistent recipient chimerism and relapse
OUTLINE This is a randomized open-label multicenter study Patients are stratified according to specific combinations of risk intermediate CR2 vs high CR2 vs high CR1 donor type matched sibling vs unrelated or other related and stem cell source filgrastim G-CSF-primed bone marrow vs unprimed bone marrow vs bone marrow vs peripheral blood vs umbilical cord blood
PREPARATIVE REGIMEN Patients undergo total-body irradiation twice daily on days -8 to -6 and receive thiotepa IV on days -5 and -4 and cyclophosphamide IV on days -3 and -2
ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION Patients undergo allogeneic hematopoietic stem cell transplantation on day 0
GRAFT-VERSUS-HOST DISEASE GVHD PROPHYLAXIS Patients are randomized to 1 of 2 treatment arms
ARM I experimental Patients receive tacrolimus IV continuously or orally when able daily beginning on day -2 followed by a taper beginning on day 42 and continuing until day 98 for patients undergoing matched sibling donor transplantation OR tacrolimus IV continuously or orally daily beginning on day -2 followed by a taper beginning on day 100 and continuing until day 180 for patients undergoing related unrelated or cord blood donor transplantation in the absence of GVHD Patients also receive methotrexate IV on days 1 3 and 6 for patients with matched sibling and umbilical cord blood donors OR days 1 3 6 and 11 for patients with unrelated bone marrow and peripheral blood stem cell donors and oral sirolimus daily beginning on day 0 followed by a taper beginning on day 180 and continuing until day 207
ARM II control Patients receive tacrolimus and methotrexate as in arm I
After completion of study treatment patients are followed periodically for approximately 5 years
I Compare the post-transplant 2-year event-free survival of pediatric patients with intermediate-risk or high-risk acute lymphoblastic leukemia ALL in second complete remission or high risk ALL in first remission undergoing allogeneic hematopoietic stem cell transplantation treated with graft-versus-host disease GVHD prophylaxis comprising tacrolimus and methotrexate with or without sirolimus
SECONDARY OBJECTIVES
I Compare rates of relapses transplant-related mortality and acute and chronic GVHD in these patients
II Evaluate the relative contribution of resistance by ALL blasts to cytolytic therapy eg chemotherapyirradiation as a cause of relapse post-transplantation by correlating ALL in vivo blast resistance with in vivo sirolimus inhibition levels of the mTOR pathway in patients treated with sirolimus and altered resistance pathways in ALL blasts measured by microarray analysis
III Evaluate the relative contribution of resistance by ALL blasts to the donor immune response as a cause of relapse post-transplantation by correlating the development of donor anti-ALL T-cell response the development of acute andor chronic GVHD and the detection of altered ALL blast immunogenicity after transplant with increased minimal residual disease persistent recipient chimerism and relapse
OUTLINE This is a randomized open-label multicenter study Patients are stratified according to specific combinations of risk intermediate CR2 vs high CR2 vs high CR1 donor type matched sibling vs unrelated or other related and stem cell source filgrastim G-CSF-primed bone marrow vs unprimed bone marrow vs bone marrow vs peripheral blood vs umbilical cord blood
PREPARATIVE REGIMEN Patients undergo total-body irradiation twice daily on days -8 to -6 and receive thiotepa IV on days -5 and -4 and cyclophosphamide IV on days -3 and -2
ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION Patients undergo allogeneic hematopoietic stem cell transplantation on day 0
GRAFT-VERSUS-HOST DISEASE GVHD PROPHYLAXIS Patients are randomized to 1 of 2 treatment arms
ARM I experimental Patients receive tacrolimus IV continuously or orally when able daily beginning on day -2 followed by a taper beginning on day 42 and continuing until day 98 for patients undergoing matched sibling donor transplantation OR tacrolimus IV continuously or orally daily beginning on day -2 followed by a taper beginning on day 100 and continuing until day 180 for patients undergoing related unrelated or cord blood donor transplantation in the absence of GVHD Patients also receive methotrexate IV on days 1 3 and 6 for patients with matched sibling and umbilical cord blood donors OR days 1 3 6 and 11 for patients with unrelated bone marrow and peripheral blood stem cell donors and oral sirolimus daily beginning on day 0 followed by a taper beginning on day 180 and continuing until day 207
ARM II control Patients receive tacrolimus and methotrexate as in arm I
After completion of study treatment patients are followed periodically for approximately 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 |
|---|---|---|---|
| U10CA098543 | NIH | Childrens Oncology Group | httpsreporternihgovquickSearchU10CA098543 |
| NCI-2009-01068 | REGISTRY | None | None |
| CDR0000500131 | OTHER | None | None |
| COG-PBMTC-ONCO51 | OTHER | None | None |
| COG-ASCT0431 | OTHER | None | None |