A Phase 1/2 interventional study of CD3/CD19 depleted leukocytes and CD45RA depleted leukocytes in Sickle Cell Anemia, Beta-thalassemia Major and Diamond-blackfan Anemia, sponsored by Paul Szabolcs. Recruiting at 1 site in United States. Open to participants aged 5 Years to 40 Years. Per ClinicalTrials.gov, last updated 2026-08-13.
Sponsored by Paul Szabolcs · Phase 1/2, Interventional, and Treatment
The purpose of this study is to evaluate what effect, if any, mismatched unrelated volunteer donor and/or haploidentical related donor stem cell transplant may have on severe sickle cell disease and other transfusion dependent anemias. By using mismatched unrelated volunteer donor and/or haploidentical related donor stem cells, this study will increase the number of patients who can undergo a stem cell transplant for their specified disease. Additionally, using a T-cell depleted approach should reduce the incidence of graft-versus-host disease which would otherwise be increased in a mismatched transplant setting.
CD3/CD19 depletion of mismatched donor grafts in the setting of reduced intensity, immune-ablative conditioning for patients with sickle cell disease and other transfusion-dependent anemias should sufficiently achieve engraftment while decreasing the incidence of treatment-related toxicities and achieving an acceptable incidence of graft versus host disease. Utilizing mismatched unrelated volunteer donors and haploidentical related donors will increase the number of patients able to undergo hematopoietic stem cell transplant (HSCT) for these diseases. Additionally, the institutional availability of virus-specific, donor-derived cytotoxic T lymphocytes should address complicated viral infections refractory to standard anti-viral therapy.
The purpose is to:
1,134 studies on the registry are indexed under Anemia, Sickle Cell; 238 are open to participants now.
This study's planned enrollment of 5 is below the median of 40 across 769 interventional studies indexed under Anemia, Sickle Cell.
Browse Anemia, Sickle Cell studies →Paul Szabolcs is the lead sponsor of 9 studies on the registry; 9 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria
Diagnosis of Sickle Cell Disease ( SS, Sβ0-thalassemia) complicated by any of the following:
OR Diagnosis of beta-thalassemia or Diamond-Blackfan anemia complicated by transfusion dependence with evidence of iron overload.
Adequate function of other organ systems as measured by:
Patient Exclusion Criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All patients will receive a CD3+/CD19+ depleted stem cell transplant. In this study, the investigators will use HLA mismatched unrelated or haploidentical related donor peripheral blood stem cells. Prior to transplantation, the marrow (90-95%) will be negatively selected for CD3/CD19 using the ClinicMACs® depletion device. The remaining (5-10%) will undergo CD45+RA+ depletion and be frozen for future use as an immune boost. Subjects will undergo hematopoietic stem cell transplant utilizing CD3+/CD19+ depleted cells following conditioning therapy.
Biological: CD3/CD19 depleted leukocytes · Biological: CD45RA depleted leukocytes · Drug: Hydroxyurea · Drug: Rituximab · Drug: Alemtuzumab · Drug: Fludarabine · Drug: Thiotepa
Negative selection for CD3+/CD19+ cells will be performed on the CliniMACS® depletion device.
Negative selection for CD45RA will be performed on the CliniMACS® depletion device.
Sickle Cell Disease Conditioning
Also known as: HU, Hydrea
Sickle Cell Disease Conditioning
Also known as: Rituxan
Sickle Cell Disease Conditioning
Also known as: Campath-1H
Sickle Cell Disease Conditioning
Also known as: Fludara
Sickle Cell Disease Conditioning
Graft rejection
How frequent, if any, graft rejection occurs
Time frame: Day -30 through study completion, an average of 2 years
Post Transplant treatment related mortality
Number of deaths that occurred from treatment
Time frame: By day 100
Acute Graft versus host disease
The number of patients who develop acute graft versus host disease (GVHD)post transplant
Time frame: Day 0 through study completion, an average of 2 years
Chronic Graft versus host disease
The number of patients who develop chronic graft versus host disease (GVHD) post transplant
Time frame: Day 0 through study completion, an average of 2 years
Post Transplant treatment related mortality
Number of deaths that occurred from treatment
Time frame: Day 180
Post Transplant treatment related mortality
Number of deaths that occurred from treatment
Time frame: 1 year
Neutrophil recovery
≥ 0.5 x 103/μL neutrophils for three consecutive days tested on different days.
Time frame: Day 0 through study completion, an average of 2 years
Donor Cell Engraftment
≥ 5% donor cells on day +42 and ≥ 10% donor cells on day +100. We will record if subjects have attained robust donor cell engraftment (\> 50% donor chimerism at 180 days).
Time frame: From Day 0, Day 42, Day 100 and Day 180. Further testing can be done if clinically indicated up to 2 years post transplant
Neurological complications
To evaluate the incidence of neurological complications
Time frame: Day 0 through study completion, an average of 2 years
Immune reconstitution
The pace of systemic immune reconstitution
Time frame: Day 0 through study completion, an average of 2 years
Cytomegalovirus (CMV) infection
Incidence of CMV infection by Polymerase chain reaction (PCR) as clinically indicated
Time frame: Day 0 through study completion, an average of 2 years
Donor Lymphocyte Infusions response
Evaluate for delayed immune reconstitution, mixed chimerism or viral reactivation
Time frame: Day 0 through study completion, an average of 2 years
Response to donor-derived virus-specific cytotoxic T-cell therapy
Activation or reactivation of Cytomegalovirus (CMV), Epstein-Barr Virus (EBV) or adenovirus testing by PCR
Time frame: Day 0 through study completion, an average of 2 years
Sickle Cell disease phenotype recurrence
The incidence of Sickle Cell recurrence as clinical evidence of vaso occlusive crisis, detection of HgbS\>25% and acute chest syndrome.
Time frame: Day 0 through study completion, an average of 2 years
Recurrence of transfusion-dependence
Chronic transfusion therapy defined as \> 8 packed red blood cell transfusions per year in the year prior to enrollment and/or evidence of red blood cell alloimmunization.
Time frame: Day 0 through study completion, an average of 2 years
Organ toxicity
Incidence of Grade 3-4
Time frame: Day 0 through study completion, an average of 2 years
Long-term complications-Sterility, endocrinopathy, and secondary malignancy
Incidence of long term complications
Time frame: Day 0 through study completion, an average of 2 years
Pediatric Quality of Life Inventory
Measures Pain/Hurt ,Pain Impact,Pain Management/Control ,Worry ,Emotions ,Treatment , Communication
Time frame: Baseline through study completion, an average of 2 years
Platelet Recovery
Platelet count of ≥ 20,000/μL without platelet transfusion in the previous 7 days.
Time frame: Day 0 through study completion, an average of 2 years
Adult Sickle Cell Quality of Life Measurement System (ASCQ)
Patient reported outcome measurement system that assesses the physical, social and emotional impact of Sickle Cell Disease.
Time frame: Baseline through study completion, an average of 2 years
Plan to share: No
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Studies of the drugs tested here: Hydroxyurea · Rituximab · Alemtuzumab · Fludarabine · Thiotepa
Paul Szabolcs