Trial Outcomes & Findings for Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies (NCT NCT04523376)

Last Updated: 2026-04-28

Results Overview

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)

Recruitment status

COMPLETED

Study phase

Target enrollment

8 participants

Primary outcome timeframe

Up to 1 year post-transplantation

Results posted on

2026-04-28

Participant Flow

Participant milestones

Participant milestones
Measure	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. 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	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. 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
Overall Study STARTED	7	1
Overall Study COMPLETED	5	1
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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. 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	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. 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
Overall Study Graft Failure requiring change in treatment plan	2	0

Baseline Characteristics

Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sickle Cell Disease n=7 Participants 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. 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	Beta Thalassemias Major n=1 Participants 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. 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	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	6 Participants n=9 Participants	1 Participants n=24 Participants	7 Participants n=23 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=9 Participants	0 Participants n=24 Participants	1 Participants n=23 Participants
Age, Categorical >=65 years	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants
Age, Continuous	10.7 years n=9 Participants	16 years n=24 Participants	11.25 years n=23 Participants
Sex: Female, Male Female	3 Participants n=9 Participants	1 Participants n=24 Participants	4 Participants n=23 Participants
Sex: Female, Male Male	4 Participants n=9 Participants	0 Participants n=24 Participants	4 Participants n=23 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants
Race (NIH/OMB) Asian	0 Participants n=9 Participants	1 Participants n=24 Participants	1 Participants n=23 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants
Race (NIH/OMB) Black or African American	7 Participants n=9 Participants	0 Participants n=24 Participants	7 Participants n=23 Participants
Race (NIH/OMB) White	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=9 Participants	1 Participants n=24 Participants	8 Participants n=23 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants	0 Participants n=24 Participants	0 Participants n=23 Participants
Region of Enrollment United States	7 participants n=9 Participants	1 participants n=24 Participants	8 participants n=23 Participants
HLA Donor Match Category (10/10 Matched vs 9/10 Mismatched) Matched Donor (10/10)	4 participants n=9 Participants	0 participants n=24 Participants	4 participants n=23 Participants
HLA Donor Match Category (10/10 Matched vs 9/10 Mismatched) Mismatched Donor (9/10)	3 participants n=9 Participants	1 participants n=24 Participants	4 participants n=23 Participants

PRIMARY outcome

Timeframe: Up to 1 year post-transplantation

Outcome measures

Outcome measures
Measure	Sickle Cell Disease n=7 Participants 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. 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	Beta Thalassemias Major n=1 Participants 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. 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
Rate of Graft Failure	2 participants	0 participants

PRIMARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Sickle Cell Disease n=7 Participants 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. 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	Beta Thalassemias Major n=1 Participants 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. 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
Time to Neutrophil Engraftment	15 Days Interval 13.0 to 17.0	13 Days Interval 13.0 to 13.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Sickle Cell Disease n=7 Participants 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. 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	Beta Thalassemias Major n=1 Participants 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. 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
Incidence of Acute Graft vs. Host Disease (GVHD)	2 participants	0 participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Sickle Cell Disease n=7 Participants 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. 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	Beta Thalassemias Major n=1 Participants 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. 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
Incidence of Chronic Graft vs. Host Disease (GVHD)	1 participants	0 participants

SECONDARY outcome

Timeframe: Up to 100 days post-transplantation

Number of subjects deaths that were related to study treatment

Outcome measures

Outcome measures
Measure	Sickle Cell Disease n=7 Participants 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. 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	Beta Thalassemias Major n=1 Participants 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. 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
Number of Deaths Due to Treatment	1 participants	0 participants

SECONDARY outcome

Timeframe: Up to 1 year post-transplantation

Number of patients without complications or events

Outcome measures

Outcome measures
Measure	Sickle Cell Disease n=7 Participants 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. 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	Beta Thalassemias Major n=1 Participants 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. 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
Probability of Event-free Survival (EFS)	5 participants	1 participants

SECONDARY outcome

Timeframe: 1 year post-transplantation

Number of patients with the following survival outcome: one-year overall survival (OS)

Outcome measures

Outcome measures
Measure	Sickle Cell Disease n=7 Participants 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. 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	Beta Thalassemias Major n=1 Participants 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. 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
Probability of Overall Survival (OS)	6 participants	1 participants

SECONDARY outcome

Timeframe: Up to 1 year post-transplantation

Number of patients experiencing viral reactivation requiring therapy and symptomatic viral infections, including CMV, adenovirus, and EBV

Outcome measures

Outcome measures
Measure	Sickle Cell Disease n=7 Participants 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. 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	Beta Thalassemias Major n=1 Participants 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. 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
Incidence of Viral Reactivation and Symptomatic Viral Infection	5 participants	0 participants

Adverse Events

Sickle Cell Disease

Serious events: 2 serious events

Other events: 7 other events

Deaths: 1 deaths

Beta Thalassemias Major

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sickle Cell Disease n=7 participants at risk 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. 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	Beta Thalassemias Major n=1 participants at risk 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. 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
Blood and lymphatic system disorders Secondary graft failure	28.6% 2/7 • Number of events 2 • Subjects were followed up to 2 years post-transplantation	0.00% 0/1 • Subjects were followed up to 2 years post-transplantation

Other adverse events

Other adverse events
Measure	Sickle Cell Disease n=7 participants at risk 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. 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	Beta Thalassemias Major n=1 participants at risk 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. 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
Skin and subcutaneous tissue disorders Grade 2 acute graft vs host disease	14.3% 1/7 • Number of events 1 • Subjects were followed up to 2 years post-transplantation	0.00% 0/1 • Subjects were followed up to 2 years post-transplantation
Skin and subcutaneous tissue disorders Mild Chronic GVHD	14.3% 1/7 • Number of events 1 • Subjects were followed up to 2 years post-transplantation	0.00% 0/1 • Subjects were followed up to 2 years post-transplantation
Hepatobiliary disorders Grade 3 sinusoidal obstruction syndrome	0.00% 0/7 • Subjects were followed up to 2 years post-transplantation	100.0% 1/1 • Number of events 1 • Subjects were followed up to 2 years post-transplantation
Blood and lymphatic system disorders Grade 3 sepsis	14.3% 1/7 • Number of events 1 • Subjects were followed up to 2 years post-transplantation	0.00% 0/1 • Subjects were followed up to 2 years post-transplantation
Blood and lymphatic system disorders Grade 4 sepsis	28.6% 2/7 • Number of events 2 • Subjects were followed up to 2 years post-transplantation	0.00% 0/1 • Subjects were followed up to 2 years post-transplantation
Blood and lymphatic system disorders CMV reactivation	28.6% 2/7 • Number of events 2 • Subjects were followed up to 2 years post-transplantation	100.0% 1/1 • Number of events 1 • Subjects were followed up to 2 years post-transplantation
Renal and urinary disorders BK reactivation	0.00% 0/7 • Subjects were followed up to 2 years post-transplantation	100.0% 1/1 • Number of events 1 • Subjects were followed up to 2 years post-transplantation
Nervous system disorders Stroke	14.3% 1/7 • Number of events 1 • Subjects were followed up to 2 years post-transplantation	0.00% 0/1 • Subjects were followed up to 2 years post-transplantation

Additional Information

Timothy Olson, MD PhD

Children's Hospital of Philadelphia

Phone: 215-590-2820

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place