Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies

NCT04523376 | Completed Results DMC FDA Device

• 1 other identifier: 19-017141
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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).

Conditions

Sickle Cell Disease; Thalassemia Major

Outcome Measures

Primary Outcomes (4)

• Rate of Graft Failure

  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

  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)

  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)

  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 Outcomes (4)

• Number of Deaths Due to Treatment

  Up to 100 days post-transplantation

• Probability of Event-free Survival (EFS)

  Up to 1 year post-transplantation

• Probability of Overall Survival (OS)

  1 year post-transplantation

• Incidence of Viral Reactivation and Symptomatic Viral Infection

  Up to 1 year post-transplantation

Study Arms (2)

Sickle Cell Disease

EXPERIMENTAL

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

Beta Thalassemias Major

EXPERIMENTAL

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

Interventions

CliniMACS DEVICE

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

Beta Thalassemias Major; Sickle Cell Disease

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Timothy Olson: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (63)

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MeSH Terms

Conditions

Anemia, Sickle Cell; beta-Thalassemia

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thalassemia

Limitations and Caveats

Our study is limited by a small sample size, and further multicenter analyses are necessary to firmly establish our conclusions.

Results Point of Contact

• Title: Timothy Olson, MD PhD
• Organization: Children's Hospital of Philadelphia

cttsbmtintake@chop.edu

215-590-2820

Study Officials

• Timothy Olson, MD, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 21, 2020
• Study Start: May 14, 2020
• Primary Completion: June 23, 2025
• Study Completion: October 1, 2025
• Last Updated: April 28, 2026
• Results First Posted: April 28, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)