CompletedNCT04523376Updated Apr 28, 2026Results posted

Pilot Study PBSCT With TCRab Depletion For Hemoglobinopathies

An interventional study of CliniMACS in Sickle Cell Disease and Thalassemia Major, sponsored by Timothy Olson. Completed at 1 site in United States. Open to participants aged 2 Years to 25 Years. Per ClinicalTrials.gov, last updated 2026-04-28.

Sponsored by Timothy Olson · Not applicable, Interventional, and Treatment

From the registry’s dates

Registered 3 months after the study started (first participant enrolled May 2020, registered Aug 2020).

Phase: Not applicable
Study type: Interventional
Enrollment: 8
Allocation: Non-randomized
Ages: 2 Years to 25 Years
Sex: All

Study 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).

Read the 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.

Conditions studied

Sickle Cell Disease
Thalassemia Major

Browse trials for

In context

Anemia, Sickle Cell

1,103 studies on the registry are indexed under Anemia, Sickle Cell; 235 are open to participants now.

This study's enrollment of 8 is below the median of 40 across 750 interventional studies indexed under Anemia, Sickle Cell.

Browse Anemia, Sickle Cell studies →

Lead sponsor

This is the only study on the registry with Timothy Olson as lead sponsor.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 2 Years to 25 Years
Sexes eligible: All
Accepts healthy volunteers: No

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 design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 8 participants (actual)

Study arms

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
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

Interventions

DeviceCliniMACS
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 researchers measure

Primary outcomes

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)
Time frame: 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)
Time frame: 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.
Time frame: 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
Time frame: Up to two years post-transplantation

Secondary outcomes

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

Results

Posted Apr 28, 2026

Limitations and caveats

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

Participant flow

Participant flow — Overall Study
Milestone	Sickle Cell Disease	Beta Thalassemias Major
Started	7	1
Completed	5	1
Not completed	2	0
Withdrew: Graft failure requiring change in treatment plan	2	0

Outcome measures

PrimaryRate 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)

Time frame:: Up to 1 year post-transplantation
Reported as:: Number · participants

Rate of Graft Failure
participants	Sickle Cell Disease	Beta Thalassemias Major
Rate of Graft Failure	2	0

PrimaryTime to Neutrophil Engraftment

Number of days to neutrophil engraftment (first day of ANC \>500/µl for the first of 3 consecutive days)

Time frame:: Up to 60 days post-transplantation
Reported as:: Mean · Days

Time to Neutrophil Engraftment
Days	Sickle Cell Disease	Beta Thalassemias Major
Time to Neutrophil Engraftment	15 (13 to 17)	13 (13 to 13)

PrimaryIncidence 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.

Time frame:: Up to 100 days post-transplantation
Reported as:: Number · participants

Incidence of Acute Graft vs. Host Disease (GVHD)
participants	Sickle Cell Disease	Beta Thalassemias Major
Incidence of Acute Graft vs. Host Disease (GVHD)	2	0

PrimaryIncidence 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

Time frame:: Up to two years post-transplantation
Reported as:: Number · participants

Incidence of Chronic Graft vs. Host Disease (GVHD)
participants	Sickle Cell Disease	Beta Thalassemias Major
Incidence of Chronic Graft vs. Host Disease (GVHD)	1	0

SecondaryNumber of Deaths Due to Treatment

Number of subjects deaths that were related to study treatment

Time frame:: Up to 100 days post-transplantation
Reported as:: Number · participants

Number of Deaths Due to Treatment
participants	Sickle Cell Disease	Beta Thalassemias Major
Number of Deaths Due to Treatment	1	0

SecondaryProbability of Event-free Survival (EFS)

Number of patients without complications or events

Time frame:: Up to 1 year post-transplantation
Reported as:: Number · participants

Probability of Event-free Survival (EFS)
participants	Sickle Cell Disease	Beta Thalassemias Major
Probability of Event-free Survival (EFS)	5	1

SecondaryProbability of Overall Survival (OS)

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

Time frame:: 1 year post-transplantation
Reported as:: Number · participants

Probability of Overall Survival (OS)
participants	Sickle Cell Disease	Beta Thalassemias Major
Probability of Overall Survival (OS)	6	1

SecondaryIncidence of Viral Reactivation and Symptomatic Viral Infection

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

Time frame:: Up to 1 year post-transplantation
Reported as:: Number · participants

Incidence of Viral Reactivation and Symptomatic Viral Infection
participants	Sickle Cell Disease	Beta Thalassemias Major
Incidence of Viral Reactivation and Symptomatic Viral Infection	5	0

Adverse events

Collected over Subjects were followed up to 2 years post-transplantation. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Sickle Cell Disease	1/7 (14.3%)	2/7 (28.6%)	7/7 (100%)
Beta Thalassemias Major	0/1 (0%)	0/1 (0%)	1/1 (100%)

Most frequent serious events

Most frequent serious events
Event	Sickle Cell Disease	Beta Thalassemias Major
Secondary graft failureBlood and lymphatic system disorders	2/7	0/1

Most frequent other events

Most frequent other events
Event	Sickle Cell Disease	Beta Thalassemias Major
Grade 3 sinusoidal obstruction syndromeHepatobiliary disorders	0/7	1/1
CMV reactivationBlood and lymphatic system disorders	2/7	1/1
BK reactivationRenal and urinary disorders	0/7	1/1
Grade 4 sepsisBlood and lymphatic system disorders	2/7	0/1
Grade 2 acute graft vs host diseaseSkin and subcutaneous tissue disorders	1/7	0/1
Mild Chronic GVHDSkin and subcutaneous tissue disorders	1/7	0/1
Grade 3 sepsisBlood and lymphatic system disorders	1/7	0/1
StrokeNervous system disorders	1/7	0/1

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Sickle Cell Disease	Beta Thalassemias Major	Total
<=18 years	6	1	7
Between 18 and 65 years	1	0	1
>=65 years	0	0	0

Age, Continuous
Age, Continuous(years)	Sickle Cell Disease	Beta Thalassemias Major	Total
Mean	10.7 (4 to 18)	16 (16 to 16)	11.25 (4 to 18)

Sex: Female, Male
Sex: Female, Male(Participants)	Sickle Cell Disease	Beta Thalassemias Major	Total
Female	3	1	4
Male	4	0	4

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Sickle Cell Disease	Beta Thalassemias Major	Total
American Indian or Alaska Native	0	0	0
Asian	0	1	1
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	7	0	7
White	0	0	0
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Sickle Cell Disease	Beta Thalassemias Major	Total
Hispanic or Latino	0	0	0
Not Hispanic or Latino	7	1	8
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Sickle Cell Disease	Beta Thalassemias Major	Total
United States	7	1	8

HLA Donor Match Category (10/10 Matched vs 9/10 Mismatched)
HLA Donor Match Category (10/10 Matched vs 9/10 Mismatched)(participants)	Sickle Cell Disease	Beta Thalassemias Major	Total
Matched Donor (10/10)	4	0	4
Mismatched Donor (9/10)	3	1	4

Study locations

1 site

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

References and documents

Publications

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Study documents

Protocol and statistical analysis plan · Nov 25, 2022
Informed consent form · Dec 23, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 28, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04523376
Lead sponsor: Timothy Olson
Responsible party: Timothy Olson (Attending Physician, Children's Hospital of Philadelphia) — Sponsor-investigator
First posted: Aug 21, 2020
Start date: May 14, 2020
Primary completion: Jun 23, 2025
Completion: Oct 1, 2025
Results posted: Apr 28, 2026
Last update: Apr 28, 2026

Study contacts

Timothy Olson, MD, PhD

principal investigator · Children's Hospital of Philadelphia

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: Yes

View the source record on ClinicalTrials.gov ↗

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