A Phase 1/2 interventional study of CD3/CD19 negative allogeneic hematopoietic stem cells in Severe Combined Immunodeficiency (SCID), Immunodeficiency With Predominant T-cell Defect, Unspecified and Severe Chronic Neutropenia, sponsored by Paul Szabolcs. Enrolling by invitation at 1 site in United States. Open to participants aged 5 Years to 45 Years. Per ClinicalTrials.gov, last updated 2025-12-15.
Sponsored by Paul Szabolcs · Phase 1/2, Interventional, and Treatment
The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-45 years with primary immunodeficiency (PID) and end-stage lung disease.
This is an original IND for an investigator initiated phase I/II study. The primary purpose of the study is to evaluate the safety and efficacy of performing bilateral orthotopic lung transplantation (BOLT) followed by cadaveric, partially HLA-matched CD3+/CD19+-depleted hematopoietic stem cell transplantation (HSCT) from the same donor for patients with primary immunodeficiency diseases (PID) and end-stage lung disease. For many patients with primary immunodeficiencies, HSCT is a curative, life-saving therapy, resulting in restoration of function in the immune system. Patients with primary immunodeficiencies often develop pulmonary complications as a result of chronic or recurrent infections, making them ineligible for HSCT due to the high risk of mortality and pulmonary complications. Lung transplant prior to HSCT would allow for restoration of pulmonary function prior to HSCT, allowing PID patients to proceed to HSCT, which would be curative for the patient's underlying immunodeficiency. As a secondary aim after successful engraftment with donor bone marrow, there is realistic hope for tolerating planned withdrawal of immunosuppression achieving eventual freedom from all immunosuppressive drugs and attaining a tolerant state.
59 studies on the registry are indexed under Severe Combined Immunodeficiency; 14 are open to participants now.
This study's planned enrollment of 16 is above the median of 10 across 31 interventional studies indexed under Severe Combined Immunodeficiency.
Browse Severe Combined Immunodeficiency 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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients must have evidence of an underlying primary immunodeficiency for which BMT is clinically indicated.
Examples of such diseases include, but are not limited to:
Exclusion Criteria
Individuals who meet any of these criteria are not eligible for this study:
Eligibility Criteria to proceed to Bone Marrow Transplant
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 number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
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 yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
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.
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.
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.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
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.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
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.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
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.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
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.
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.
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.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
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.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All patients will receive a double lung transplant followed by a hematopoietic stem cell transplant. The lungs and stem cells are from the same partially HLA-matched cadaveric donor. Prior to transplantation, the marrow will be negatively selected for CD3/CD19 using a CliniMACS® depletion device.
Biological: CD3/CD19 negative allogeneic hematopoietic stem cells
Negative selection for CD3/CD19 will be performed on a CliniMACS® depletion device within 36 hours of collection and given at time no less than 8 weeks post lung transplant.
Safety: Death
How many, if any, patients die.
Time frame: Up to 2 years post stem cell transplant
Safety: Engraftment syndrome
How many, if any, patients develop engraftment syndrome.
Time frame: Up to 2 years post stem cell transplant
Safety: Engraftment failure
How many patients, if any, develop engraftment failure.
Time frame: Up to 2 years post stem cell transplant
Safety: Rituximab
The number of grade 4 and 5 events potentially related to rituximab.
Time frame: Up to 2 years post stem cell transplant
Efficacy: BOS score
Bronchiolitis Obliterans Syndrome (BOS) score for all patients who receive both lungs and stem cell transplants.
Time frame: 1 year post stem cell transplant
Efficacy: T-cell chimerism
The number of patients who have ≥ 25% donor T-cell chimerism.
Time frame: 1 year post stem cell transplant
Efficacy: Myeloid chimerism
The number of patients with myeloid disorders (e.g. CGD) who attain ≥ 10% myeloid chimerism.
Time frame: 1 year post stem cell transplant
Efficacy: B-cell chimerism
The number of patients with B-cell disorders who attain ≥ 10% B-cell chimerism.
Time frame: 1 year post stem cell transplant
Feasibility of meeting BMT eligibility critieria
The number of patients who are able to proceed to BMT within 6 months following lung transplant.
Time frame: Up to 2 years post stem cell transplant
Tolerance
Development of tolerance to both the host and pulmonary graft.
Time frame: Up to 2 years post stem cell transplant
Long-term complications
Long-term complications of combined solid organ and BMT.
Time frame: Up to 2 years post stem cell transplant
Graft failure
The number of patients who develop graft failure.
Time frame: Up to 2 years post stem cell transplant
Acute cellular rejection
The number of patients who develop acute cellular rejection.
Time frame: Up to 2 years post stem cell transplant
Acute graft-versus-host disease (GVHD)
The number of patient who develop acute graft-versus-host disease (GVHD).
Time frame: Up to 2 years post stem cell transplant
Chronic graft-versus-host disease (GVHD)
The number of patient who develop chronic graft-versus-host disease (GVHD).
Time frame: Up to 2 years post stem cell transplant
Ability to withdraw immunosuppression
The number of patients who are able to start immunosuppression withdrawal.
Time frame: 1 year post stem cell transplant
Time to withdraw immunosuppression
Time from BMT to withdrawal of immunosuppression.
Time frame: Up to 2 years post stem cell transplant
Pathogen-specific immunity
Time from BMT to independence from treatment dose antimicrobial drugs.
Time frame: Up to 2 years post stem cell transplant
Lymphocyte count - for T-cell lymphopenias
The number of patients who are able to achieve an age adjusted, low limit normal range lymphocyte count.
Time frame: 1 year post stem cell transplant
Chronic lung allograft dysfunction
The number of patients who develop chronic lung allograft dysfunction post-lung transplant for all subjects, lung only and lung+stem cell transplant.
Time frame: 1 year post lung transplant
Allograft failure
The number of patients who develop allograft failure post-lung transplant for all subjects, lung only and lung+stem cell transplant.
Time frame: 1 year post lung transplant
Rituximab related adverse events
The number of grade 4 or 5 adverse events possibly related to the use of rituximab.
Time frame: From the time of the first dose of rituximab up to the start of BMT conditioning.
Plan to share: No
No publications or documents are linked to this record.
Started Jun 2013 (actual). Primary completion is estimated for Nov 2026, 161 months after the start.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
No contact was published for this record. The registry link below has the sponsor’s details.
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Severe Combined Immunodeficiency →
Paul Szabolcs