Ignite Creation Date:
2024-05-05 @ 4:57 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00358657
Status:
TERMINATED
Last Update Posted:
2021-01-26
First Post:
2006-07-28
Brief Title:
Fludarabine Phosphate Cyclophosphamide and Total-Body Irradiation Followed by Donor Bone Marrow Transplant and Cyclophosphamide Mycophenolate Mofetil Tacrolimus and Sirolimus in Treating Patients With Primary Immunodeficiency Disorders or Noncancerous Inherited Disorders
Sponsor:
Fred Hutchinson Cancer Center
Organization:
Fred Hutchinson Cancer Center
Study Overview
Official Title:
HLA-Haploidentical Related Marrow Grafts for the Treatment of Primary Immunodeficiencies and Other Nonmalignant Disorders Using Conditioning With Low-Dose Cyclophosphamide TBI and Fludarabine and Postgrafting Cyclophosphamide
Status:
TERMINATED
Status Verified Date:
2021-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Low accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial studies the side effects of fludarabine phosphate cyclophosphamide and total-body irradiation followed by donor bone marrow transplant and cyclophosphamide mycophenolate mofetil tacrolimus and sirolimus in treating patients with primary immunodeficiency disorders or noncancerous inherited disorders Giving low doses of chemotherapy and total-body irradiation before a bone marrow transplant helps prepare the patients body to accept the incoming donors bone marrow and decrease the risk that the patients immune system will reject 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 called graft versus host disease Giving cyclophosphamide mycophenolate mofetil tacrolimus and sirolimus after the transplant may help decrease this from happening
Detailed Description:
PRIMARY OBJECTIVE
I Determine safety of nonmyeloablative conditioning and hematopoietic cell transplantation HCT from human leukocyte antigen HLA-haploidentical related donors for patients with nonmalignant inherited disorders who do not have an HLA-matched related or unrelated donor
SECONDARY OBJECTIVES
I Determine whether nonmyeloablative conditioning and HCT from an HLA-haploidentical related donor graft can establish mixed chimerism 5 cluster of differentiation CD3 donor T-cell chimerism in patients with nonmalignant inherited disorders
II Transplant related mortality at day 100
III Incidence and severity of graft-versus-host disease GHVD
IV Immune reconstitution
V Infections during the first 200 days after HCT
OUTLINE
NONMYELOABLATIVE CONDITIONING REGIMEN Patients receive fludarabine phosphate intravenously IV over 1 hour on days -6 to -2 cyclophosphamide IV over 1 hour on days -6 and -5 and undergo total body irradiation on day -1
TRANSPLANTATION Patients undergo allogeneic bone marrow transplant on day 0
POST-TRANSPLANT IMMUNOSUPPRESSION Patients receive cyclophosphamide IV over 1 hour on days 3 and 4 and mycophenolate mofetil orally PO every 8 hours on days 5-30 then twice daily BID to day 40 and then if there is no evidence of active GVHD and donor engraftment is 95 or by principal investigator PI approval taper until approximately day 96 or faster at discretion of PI Patients also receive tacrolimus IV continuously over 22-24 hours starting on day 5 post-transplant and continue on tacrolimus through day 100 followed by a taper to approximately day 180 if there is no evidence of GVHD and their graft is doing well Patients may convert to oral tacrolimus given BID or three times daily TID when the patient is able to take medications orally and has a therapeutic drug level In addition patients will receive sirolimus PO beginning on day 5 through day 180 followed by a taper to approximately day 210 if there is no evidence of GVHD and their graft is doing well
After completion of study treatment patients are followed up at 6 12 18 and 24 months and then annually for 5 years
I Determine safety of nonmyeloablative conditioning and hematopoietic cell transplantation HCT from human leukocyte antigen HLA-haploidentical related donors for patients with nonmalignant inherited disorders who do not have an HLA-matched related or unrelated donor
SECONDARY OBJECTIVES
I Determine whether nonmyeloablative conditioning and HCT from an HLA-haploidentical related donor graft can establish mixed chimerism 5 cluster of differentiation CD3 donor T-cell chimerism in patients with nonmalignant inherited disorders
II Transplant related mortality at day 100
III Incidence and severity of graft-versus-host disease GHVD
IV Immune reconstitution
V Infections during the first 200 days after HCT
OUTLINE
NONMYELOABLATIVE CONDITIONING REGIMEN Patients receive fludarabine phosphate intravenously IV over 1 hour on days -6 to -2 cyclophosphamide IV over 1 hour on days -6 and -5 and undergo total body irradiation on day -1
TRANSPLANTATION Patients undergo allogeneic bone marrow transplant on day 0
POST-TRANSPLANT IMMUNOSUPPRESSION Patients receive cyclophosphamide IV over 1 hour on days 3 and 4 and mycophenolate mofetil orally PO every 8 hours on days 5-30 then twice daily BID to day 40 and then if there is no evidence of active GVHD and donor engraftment is 95 or by principal investigator PI approval taper until approximately day 96 or faster at discretion of PI Patients also receive tacrolimus IV continuously over 22-24 hours starting on day 5 post-transplant and continue on tacrolimus through day 100 followed by a taper to approximately day 180 if there is no evidence of GVHD and their graft is doing well Patients may convert to oral tacrolimus given BID or three times daily TID when the patient is able to take medications orally and has a therapeutic drug level In addition patients will receive sirolimus PO beginning on day 5 through day 180 followed by a taper to approximately day 210 if there is no evidence of GVHD and their graft is doing well
After completion of study treatment patients are followed up at 6 12 18 and 24 months and then annually for 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 |
|---|---|---|---|
| RG9213024 | OTHER | Fred HutchUniversity of Washington Cancer Consortium | httpsreporternihgovquickSearchP30CA015704 |
| NCI-2010-00192 | REGISTRY | None | None |
| 2032 | None | None | None |
| 203200 | OTHER | None | None |
| P01HL122173 | NIH | None | None |
| P30CA015704 | NIH | None | None |