Ignite Creation Date:
2025-12-24 @ 4:46 PM
Ignite Modification Date:
2025-12-30 @ 4:57 AM
Study NCT ID:
NCT04776850
Status:
WITHDRAWN
Last Update Posted:
2024-10-24
First Post:
2021-02-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pre-transplant Immunosuppression and Donor Stem Cell Transplant for the Treatment of Severe Hemoglobinopathies
Sponsor:
M.D. Anderson Cancer Center
Organization:
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WITHDRAWN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 \>= 1:3,000 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 \> 1:15,000 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 \> 1:5,000 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 \>= 1:3,000 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 \> 1:15,000 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 \> 1:5,000 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:
True
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?: