Ignite Creation Date:
2024-05-06 @ 8:21 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06358638
Status:
RECRUITING
Last Update Posted:
2024-06-20
First Post:
2024-04-02
Brief Title:
Sickle Cell Disease Transplant Using a Nonmyeloablative Approach for Patients With Anti-donor Red Cell AntibodY
Sponsor:
Childrens National Research Institute
Organization:
Childrens National Research Institute
Study Overview
Official Title:
Sickle Cell Disease Transplant Using a Nonmyeloablative Approach Adding Daratumumab for Patients With Anti-donor Red Cell AntibodY
Status:
RECRUITING
Status Verified Date:
2024-06
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:
SUN-RAY
Brief Summary:
This multicenter prospective study seeks to determine if daratumumab given prior to HLA-identical sibling donor transplantation using alemtuzumab low dose total-body irradiation and sirolimus can prevent pure red blood cell aplasia with an acceptable safety profile in patients with anti-donor red blood cell antibodies achieving an event-free survival similar to transplanted patients without such antibodies
Detailed Description:
This study addresses an important question Can daratumumab safely be administered prior to matched sibling donor MSD nonmyeloablative hematopoietic cell transplant HCT for SCD to avoid pure red blood cell aplasia in patients at risk of this complication and thus achieve an event-free survival similar to patients without anti-donor red blood cell RBC antibodies
Patients with anti-donor RBC antibodies which includes patients with major ABO mismatch and other RBC alloantibodies against donor have largely been excluded from the nonmyeloablative HCT approach given their risk of delayed donor RBC engraftment andor hemolysis post-HCT Exclusion of these patients limits access to less toxic curative therapies for this population at risk for toxicity due to their underlying multisystem disease To address this need we propose a multicenter clinical trial of Sickle cell disease Using a Nonmyeloablative approach adding daratumumab for patients with anti-donor Red cell AntibodY SUN-RAY If successful this trial will increase access to MSD nonmyeloablative HCT in SCD and will provide important safety and efficacy data for the use of daratumumab in the pre-HCT setting as well as in patients with SCD who have limited RBC donor options due to alloimmunization
This is a phase 2 study given that the studied nonmyeloablative conditioning backbone alemtuzumab 300 cGY TBI sirolimus has been previously used effectively in both adults and children with SCD Daratumumab will be added to this backbone with a washout period of 4 weeks prior to HCT infusion Small case series have demonstrated that daratumumab is well tolerated either pre-HCT to treat patients with antibodies against mismatched donor HLA antigens or post-HCT in patients with autoimmune cytopenias The experience of the phase 2 clinical trial NCT03384654 studying daratumumab in pediatric acute lymphoblastic leukemia provides additional support for the safety and dosing of daratumumab for this study
Patients with anti-donor RBC antibodies which includes patients with major ABO mismatch and other RBC alloantibodies against donor have largely been excluded from the nonmyeloablative HCT approach given their risk of delayed donor RBC engraftment andor hemolysis post-HCT Exclusion of these patients limits access to less toxic curative therapies for this population at risk for toxicity due to their underlying multisystem disease To address this need we propose a multicenter clinical trial of Sickle cell disease Using a Nonmyeloablative approach adding daratumumab for patients with anti-donor Red cell AntibodY SUN-RAY If successful this trial will increase access to MSD nonmyeloablative HCT in SCD and will provide important safety and efficacy data for the use of daratumumab in the pre-HCT setting as well as in patients with SCD who have limited RBC donor options due to alloimmunization
This is a phase 2 study given that the studied nonmyeloablative conditioning backbone alemtuzumab 300 cGY TBI sirolimus has been previously used effectively in both adults and children with SCD Daratumumab will be added to this backbone with a washout period of 4 weeks prior to HCT infusion Small case series have demonstrated that daratumumab is well tolerated either pre-HCT to treat patients with antibodies against mismatched donor HLA antigens or post-HCT in patients with autoimmune cytopenias The experience of the phase 2 clinical trial NCT03384654 studying daratumumab in pediatric acute lymphoblastic leukemia provides additional support for the safety and dosing of daratumumab for this study
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?:
True
Is an FDA AA801 Violation?:
None