Ignite Creation Date:
2024-05-06 @ 3:49 PM
Last Modification Date:
2024-10-26 @ 1:58 PM
Study NCT ID:
NCT04776850
Status:
WITHDRAWN
Last Update Posted:
2023-02-21
First Post:
2021-02-08
Brief Title:
Pre-transplant Immunosuppression and Donor Stem Cell Transplant for the Treatment of Severe Hemoglobinopathies
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
Pre-Transplant Immunosuppression and Related Haploidentical Hematopoietic Cell Transplantation for Patients With Severe Hemoglobinopathies
Status:
WITHDRAWN
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Competing protocol opened in Adult SCT that will include pediatric patients and is now multi-center No patients enrolled on study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This clinical trial studies the effect of pre-transplant immunosuppression PTIS and donor stem cell transplant in treating patients with severe blood diseases hemoglobinopathies PTIS helps prepare the body for the transplant and lowers the risk of developing graft versus host disease GVHD Hematopoietic cells are found in the bone marrow and produce blood cells Hematopoietic cell transplantation HCT injects healthy hematopoietic cells into the body to support blood cell production PTIS and HCT may help to control severe hemoglobinopathies
Detailed Description:
PRIMARY OBJECTIVE
I To estimate event-free survival EFS at 2-years post HCT
SECONDARY OBJECTIVES
I Assess event-free survival EFS at 100 days and 1 year post HCT II Assess overall survival OS at 100 days and 1 year post HCT III 30-day transplant-related mortality TRM IV Time to platelet and neutrophil engraftment V Rate of graft failure primary and secondary through day 100 VI Incidence of acute graft-versus-host disease aGVHD by day 100 VII Incidence of chronic graft-versus-host disease cGVHD by 1 year and 2 years
VIII Rate of grade II or greater organ toxicity through day 100 IX Incidence of hepatic sinusoidal obstruction syndrome SOS by day 100 X Incidence of central nervous system CNS toxicities including posterior reversible encephalopathy syndrome PRES by day 100
XI Incidence of infectious complications through day 100
EXPLORATORY OBJECTIVES
I Effect of HCT on clinical and laboratory manifestations of hemoglobinopathies by 1 and 2 years after HCT
II Assess the pharmacokinetic profile of busulfan and thymoglobulin to better understand post-transplant outcomes
III Assess immune reconstitution kinetics post HCT
OUTLINE
DONOR-SPECIFIC ANTI-HLA DESENSITIZATION Patients with donor-specific anti-HLA antibody titers 13000 at the start of PTIS receive rituximab intravenously IV on days -69 -41 -28 and -13 and bortezomib IV over less than 1 minute on days -68 -65 -40 and -37 in the absence of unacceptable toxicity Patients with donor-specific anti-HLA antibody titers 115000 at the start of PTIS receive receive rituximab IV on days -69 -41 -28 and -13 and bortezomib IV over less than 1 minute on days -68 -65 -62 -58 -40 -37 -34 and -31 in the absence of unacceptable toxicity Patients with donor-specific anti-HLA antibody titers 15000 at the start of conditioning may also undergo plasmapheresis on day -12
PTIS Patients receive fludarabine phosphate fludarabine IV over 1 hour and dexamethasone IV over less than 1 minute on days -68 to -64 and days -40 to -36 in the absence of disease progression or unacceptable toxicity
CONDITIONING Patients receive lapine T-lymphocyte immune globulin rATG IV over 4-6 hours on days -12 to -10 fludarabine phosphate IV over 1 hour on days -8 to -4 and busulfan IV over 2 hours on days -7 to -4 in the absence of disease progression or unacceptable toxicity
TRANSPLANT Patients undergo HCT on day 0
GVHD PROPHYLAXIS Patients receive cyclophosphamide IV over 2-3 hours on days 3 and 4 in the absence of unacceptable toxicity Beginning on day 5 patients also receive tacrolimus IV continuously daily and then orally PO twice daily BID at the discretion of the treating physician for up to 12 months and mycophenolate mofetil IV or PO BID up to day 60 in the absence of unacceptable toxicity
After completion of HCT patients are followed up periodically for up to 2 years
I To estimate event-free survival EFS at 2-years post HCT
SECONDARY OBJECTIVES
I Assess event-free survival EFS at 100 days and 1 year post HCT II Assess overall survival OS at 100 days and 1 year post HCT III 30-day transplant-related mortality TRM IV Time to platelet and neutrophil engraftment V Rate of graft failure primary and secondary through day 100 VI Incidence of acute graft-versus-host disease aGVHD by day 100 VII Incidence of chronic graft-versus-host disease cGVHD by 1 year and 2 years
VIII Rate of grade II or greater organ toxicity through day 100 IX Incidence of hepatic sinusoidal obstruction syndrome SOS by day 100 X Incidence of central nervous system CNS toxicities including posterior reversible encephalopathy syndrome PRES by day 100
XI Incidence of infectious complications through day 100
EXPLORATORY OBJECTIVES
I Effect of HCT on clinical and laboratory manifestations of hemoglobinopathies by 1 and 2 years after HCT
II Assess the pharmacokinetic profile of busulfan and thymoglobulin to better understand post-transplant outcomes
III Assess immune reconstitution kinetics post HCT
OUTLINE
DONOR-SPECIFIC ANTI-HLA DESENSITIZATION Patients with donor-specific anti-HLA antibody titers 13000 at the start of PTIS receive rituximab intravenously IV on days -69 -41 -28 and -13 and bortezomib IV over less than 1 minute on days -68 -65 -40 and -37 in the absence of unacceptable toxicity Patients with donor-specific anti-HLA antibody titers 115000 at the start of PTIS receive receive rituximab IV on days -69 -41 -28 and -13 and bortezomib IV over less than 1 minute on days -68 -65 -62 -58 -40 -37 -34 and -31 in the absence of unacceptable toxicity Patients with donor-specific anti-HLA antibody titers 15000 at the start of conditioning may also undergo plasmapheresis on day -12
PTIS Patients receive fludarabine phosphate fludarabine IV over 1 hour and dexamethasone IV over less than 1 minute on days -68 to -64 and days -40 to -36 in the absence of disease progression or unacceptable toxicity
CONDITIONING Patients receive lapine T-lymphocyte immune globulin rATG IV over 4-6 hours on days -12 to -10 fludarabine phosphate IV over 1 hour on days -8 to -4 and busulfan IV over 2 hours on days -7 to -4 in the absence of disease progression or unacceptable toxicity
TRANSPLANT Patients undergo HCT on day 0
GVHD PROPHYLAXIS Patients receive cyclophosphamide IV over 2-3 hours on days 3 and 4 in the absence of unacceptable toxicity Beginning on day 5 patients also receive tacrolimus IV continuously daily and then orally PO twice daily BID at the discretion of the treating physician for up to 12 months and mycophenolate mofetil IV or PO BID up to day 60 in the absence of unacceptable toxicity
After completion of HCT patients are followed up periodically for up to 2 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
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 |
|---|---|---|---|
| NCI-2021-00365 | REGISTRY | None | None |
| 2020-0952 | OTHER | M D Anderson Cancer Center | None |