Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies

April 7, 2026 updated by: Timothy Olson

Closely Matched Unrelated Donor Peripheral Blood Stem Cell Transplantation With TCRαβ+ T Cell and B Cell Depletion For Patients With Sickle Cell Disease and Thalassemia Major

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

8

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria

Severe Sickle Cell Disease

  • Genotype: Hemoglobin SS, Hemoglobin SC, Hemoglobin SD, SOArab, or Hemoglobin SBeta thalassemia
  • Must have at least one of the following disease manifestations
  • Clinically symptomatic neurologic event (stroke) or any neurologic deficit lasting greater than 24 hours at any time prior to enrollment
  • History of two or more episodes of vaso-occlusive events (VOE) per year in the 2 years preceding enrolment. Patients must be refractory to hydroxyurea, defined as developing VOE despite receiving hydroxyurea for at least 6 months. Patients who are intolerant of hydroxyurea may also be enrolled.

Vaso-occlusive events include:

  • Acute chest syndrome
  • Pain episodes requiring intravenous pain management and/or hospitalization
  • Priapism
  • Splenic sequestration (defined as a 2 g/dL drop in hemoglobin in the setting of an acutely enlarging spleen. This will be determined as part of clinical care and prior to the research)
  • Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving ≥ 8 RBC transfusions in the year preceding enrollment to prevent sickle cell-related complications of any kind per treating hematologist's judgment.

Beta Thalassemia Major

  • Genotype: Confirmed Beta Thalassemia genotype by molecular genetic testing (May include E/Beta0 and Beta0/Beta+ genotypes)
  • Must meet clinical diagnosis of transfusion-dependent thalassemia, defined as need for ≥ 8 RBC transfusions per year in the two years preceding study enrollment.

Exclusion criteria

  • Patients who do not meet disease, organ or infectious criteria.
  • Previous Hematopoietic stem cell transplant (HSCT)
  • Patients with no suitable unrelated donor available. Patients with suitable fully matched related donor are also not eligible.
  • Pregnant females. All females of childbearing potential must have negative pregnancy test.
  • Participation in a clinical trial in which the patient receives an investigational drug must be discontinued prior to the time of initiation of transplant therapy. Specifically transplant chemotherapy should not begin until at least 3 half-lives after last use of the investigational drug.
  • Severe RBC alloimmunization, defined as inability to receive packed RBC transfusion therapy due to anti-RBC antibodies. Patients with high titer anti-donor human leukocyte antigen (HLA) antibodies detected on screening may be enrolled if they are willing to undergo HLA antibody desensitization therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sickle Cell Disease
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.
Device: CliniMACS
Peripheral blood stem cells from closely matched unrelated donors will be processed using the CliniMACS device to remove TCRalpha/beta T cells and B cells, in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique
Experimental: Beta Thalassemias Major
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.
Device: CliniMACS
Peripheral blood stem cells from closely matched unrelated donors will be processed using the CliniMACS device to remove TCRalpha/beta T cells and B cells, in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Graft Failure
Time Frame: Up to 1 year 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)
Up to 1 year post-transplantation
Time to Neutrophil Engraftment
Time Frame: 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)
Up to 60 days post-transplantation
Incidence of Acute Graft vs. Host Disease (GVHD)
Time Frame: Up to 100 days post-transplantation
Acute GvHD was assessed by the number of patients who developed acute graft-versus-host disease, graded according to current Center for International Bone Marrow Transplant Registry (CIBMTR) reporting guidelines. Grading follows established criteria based on the severity of skin, liver, and gastrointestinal involvement, including extent of rash, bilirubin elevation, and gastrointestinal symptoms (e.g., diarrhea volume). Evaluation was performed by clinical assessment and laboratory data consistent with standard transplant-related acute GvHD grading practices.
Up to 100 days post-transplantation
Incidence of Chronic Graft vs. Host Disease (GVHD)
Time Frame: Up to two years post-transplantation
Number of patients with Grade II-IV acute GVHD, Severe Grade III-IV acute GVHD, and Chronic Extensive GVHD
Up to two years post-transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Deaths Due to Treatment
Time Frame: Up to 100 days post-transplantation
Number of subjects deaths that were related to study treatment
Up to 100 days post-transplantation
Probability of Event-free Survival (EFS)
Time Frame: Up to 1 year post-transplantation
Number of patients without complications or events
Up to 1 year post-transplantation
Probability of Overall Survival (OS)
Time Frame: 1 year post-transplantation
Number of patients with the following survival outcome: one-year overall survival (OS)
1 year post-transplantation
Incidence of Viral Reactivation and Symptomatic Viral Infection
Time Frame: Up to 1 year post-transplantation
Number of patients experiencing viral reactivation requiring therapy and symptomatic viral infections, including CMV, adenovirus, and EBV
Up to 1 year post-transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Timothy Olson

Investigators

  • Principal Investigator: Timothy Olson, MD, PhD, Children's Hospital of Philadelphia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2020

Primary Completion (Actual)

June 23, 2025

Study Completion (Actual)

October 1, 2025

Study Registration Dates

First Submitted

August 19, 2020

First Submitted That Met QC Criteria

August 19, 2020

First Posted (Actual)

August 21, 2020

Study Record Updates

Last Update Posted (Actual)

April 28, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-017141

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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