Pilot Study PBSCT with TCRab Depletion for Hemoglobinopathies

Not Applicable

Active, not recruiting

• Conditions: Sickle Cell Disease; Thalassemia Major
• Interventions: Device: CliniMACS

• Registration Number: NCT04523376
• Lead Sponsor: Timothy Olson

Brief Summary

This is a single arm pilot study of peripheral stem cell transplantation (PSCT) with ex vivo t-cell receptor alpha beta+(TCRαβ+) T cell and cluster of differentiation 19+ beta (CD19+ B) cell depletion of unrelated donor (URD) grafts using the CliniMACS device in patients with sickle cell disease (SCD) and beta thalassemia major (BTM).

Detailed Description

This is a single arm pilot study of peripheral stem cell transplantation (PSCT) with ex vivo TCRαβ+ T cell and CD19+ B cell depletion of URD grafts using the CliniMACS device in patients with SCD and BTM. Apart from CliniMACS-based cell processing, PSCT will be performed according to current standards of care in the Children's Hospital of Philadelphia (CHOP) Cell Therapy and Transplant Section, including the use of a standard chemotherapy conditioning regimen and standard follow-up laboratory assessments. The study will determine efficacy of this strategy in terms of engraftment, rates of acute and chronic Graft versus Host Disease (GvHD), and one-year overall and event-free survival.

Study Timeline

• Study Start: 2020-05-14
• Study First Submitted: 2020-08-19
• Study First Submitted QC: 2020-08-19
• Study First Posted: 2020-08-21
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-25
• Primary Completion: 2026-06-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sickle Cell Disease	CliniMACS	Patients with Sickle Cell Disease (SCD) will be given previously established, disease-specific chemotherapy based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from closely matched unrelated donors.
Beta Thalassemias Major	CliniMACS	Patients with Beta Thalassemias Major (BTM) will be given previously established, disease-specific chemotherapy based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from closely matched unrelated donors.

Primary Outcome Measures

Name	Time	Method
Incidence of chronic graft vs. host disease (GVHD)	Up to three years post-transplantation	Number of patients with Grade II-IV acute GVHD, Severe Grade III-IV acute GVHD, and Chronic Extensive GVHD
Time to neutrophil engraftment	Up to 60 days post-transplantation	Number of days to neutrophil engraftment (first day of ANC \>500/µl for the first of 3 consecutive days)
Rate of graft failure	Up to 1year post-transplantation	Number of patients with primary graft failure (defined as no evidence of neutrophil engraftment by day +30 after stem cell infusion) and secondary graft failure (defined as ANC \<500 for at least 7-10 days after initial engraftment occurs in the absence of known infection or drug-mediated suppression, and confirmed by hypocellular bone marrow biopsy and/or total donor chimerism percentage from blood or bone marrow \< 10 percent)
Incidence of acute graft vs. host disease (GVHD)	Up to 100 days post-transplantation	Number of patients with acute GvHD (graded according to the current guidelines for reporting by the Center for International Bone Marrow Transplant Registry)

Secondary Outcome Measures

Name	Time	Method
Probability of overall survival (OS)	1 year post-transplantation	Number of patients with the following survival outcome: one-year overall survival (OS)
Number of deaths due to treatment	Up to 100 days post-transplantation	Number of deaths due to treatment
Probability of event-free survival (EFS)	Up to 1 year post-transplantation	Number of patients without complications or events
Incidence of viral reactivation and symptomatic viral infection	Up to 1 year post-transplantation	Number of patients experiencing viral reactivation requiring therapy and symptomatic viral infections, including CMV, adenovirus, and EBV

Trial Locations

Locations (1)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States