Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03121001|
Recruitment Status : Recruiting
First Posted : April 19, 2017
Last Update Posted : September 25, 2019
The study is a Phase II clinical trial. Patients will receive intensity modulated total body irradiation (TBI) at a dose of 3 Gy with standard fludarabine/ i.v. cyclophosphamide conditioning prior to human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplant (HSCT).
The primary objective of the study is to determine the engraftment at Day +60 following HLA-haploidentical hematopoietic stem cell transplant protocol using immunosuppressive agents and low-dose total body irradiation (TBI) for conditioning and post-transplant cyclophosphamide in patients with sickle cell disease.
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease||Drug: ATG Drug: fludarabine Drug: cyclophosphamide Radiation: Total body irradiation Procedure: Stem cell infusion Drug: Sirolimus Drug: mycophenolate mofetil||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease|
|Actual Study Start Date :||March 20, 2017|
|Estimated Primary Completion Date :||September 12, 2023|
|Estimated Study Completion Date :||September 12, 2024|
Experimental: Subject treatment
Patients will receive the following conditioning regimen: ATG, fludarabine (6 days before stem cell infusion), cyclophosphamide, and total body irradiation. The stem cell product will be infused according to BMT unit policy. Patients will also receive GVHD prophylaxis which will consist of cyclophosphamide, sirolimus, and mycophenolate mofetil according to the protocol. Post-transplant evaluation will be done as per standard care with study data collected at days 30, 60, 100, 180, 365, and annually thereafter.
0.5 mg/kg IV on day -9, and 2 mg/kg on days -8 and day -7
Other Name: Thymoglobulin®
30 mg/m2 IVPB daily for day -6 (6 days before stem cell infusion) through day -2
14.5 mg/kg IV on days -6 and -5 and 50 mg/kg/d on days +3 and +4
Radiation: Total body irradiation
3 Gy on day -1
Procedure: Stem cell infusion
Stem cell product infused according to BMT unit policy on day 0.
loading dose of 15 mg followed by 5 mg per day on day +5
Drug: mycophenolate mofetil
1 g every 8 h (until day 35) will be started on day 5
- Estimate the number of patients who engraft by Day +60 [ Time Frame: Up to Day +60 ]Patients who achieve < 5% peripheral blood donor chimerism by Day +30 and do not have a Day +60 measure will be regarded as failing to achieve full donor chimerism by Day +60; patients who achieve > 5% donor chimerism by Day +30 but do not have a Day +60 measure will be considered nonevaluable for the primary endpoint.
- Disease free survival [ Time Frame: Up to Day +60 ]Using the Kaplan-Meier method, the probability of EFS will be estimated and reported with 90% confidence intervals. The proportion of patients who are alive will also be estimated with a 90% exact binomial confidence interval. Cumulative incidences of transplant related mortality will be estimated separately using Grey's method.
- Overall survival [ Time Frame: Up to Day +60 ]Using the Kaplan-Meier method, the probability of overall survival will be estimated and reported with 90% confidence intervals. The proportion of patients who are alive will also be estimated with a 90% exact binomial confidence interval. Cumulative incidences of transplant related mortality will be estimated separately using Grey's method.
- Adverse Effects [ Time Frame: Up to Day +60 ]The cumulative incidence of acute (grade II-IV, grade III-IV) and chronic GVHD will be estimated through competing-risk analysis using Grey's method, wherein graft failure, and death are competing risks for GVHD. Other selected toxicities (including rates of infection) will be reported descriptively.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03121001
|Contact: Damiano Rondelli, MD||312 email@example.com|
|United States, Illinois|
|University of Illinois at Chicago||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Damiano Rondelli, MD 312-413-3547 firstname.lastname@example.org|
|Principal Investigator:||Damiano Rondelli, MD||University of Illinois at Chicago|