A Phase 2 interventional study of Hydroxyurea and Alemtuzumab in Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes and Inherited Metabolic Disorders (IMD), sponsored by Paul Szabolcs. Recruiting at 1 site in United States. Open to participants aged 2 Months to 55 Years. Per ClinicalTrials.gov, last updated 2025-12-15.
Sponsored by Paul Szabolcs · Phase 2, Interventional, and Treatment
The objective of this study is to evaluate the efficacy of using a reduced-intensity condition (RIC) regimen with umbilical cord blood transplant (UCBT), double cord UCBT, matched unrelated donor (MUD) bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) in patients with non-malignant disorders that are amenable to treatment with hematopoietic stem cell transplant (HSCT). After transplant, subjects will be followed for late effects and for ongoing graft success.
For some non-malignant diseases (NMD; i.e., thalassemia, sickle cell disease, most immune deficiencies) a hematopoietic stem cell transplant may be curative by healthy donor stem cell engraftment alone. HSCT in patients with NMD differs from that in malignant disorders for two important reasons: 1) these patients are typically naïve to chemotherapy and immunosuppression. This may potentially lead to difficulties with engraftment. And 2) RIC with subsequent bone marrow chimerism may be beneficial even in mixed chimerism and result in decreased transplant-related mortality (TRM). Nevertheless, any previous organ damage, as a result of the underlying disease, may remain present after the HSCT.
For other diseases (metabolic disorders, some immunodeficiencies, etc.), a transplant is not curative. For these diseases, the main intent of the transplant is to slow down, or stop, the progress of the disease. In select few cases/diseases, the presence of healthy bone marrow derived cells may even prevent progression and prevent neurological decline.
Research funds are not available to assist with enrollment on this trial.
In this research study, instead of using the standard myeloablative conditioning, the study doctor is using RIC, in which significantly lower doses of chemotherapy will be used. The lower doses may not eradicate every stem cell in the patient's bone marrow, however, in the presented combination, the intention is to eliminate already formed immune cells and provide maximum growth advantage to healthy donor stem cells. This paves the way to successful engraftment of donor stem cells. Engrafting donor stem cells can outcompete, and donor lymphocytes could suppress, the patients' surviving stem cells. With RIC, the side effects on the brain, heart, lung, liver, and other organ functions are less severe and late toxic effects should also be reduced.
The purpose of this study is to collect data from the patients undergoing reduced-intensity conditioning before HSCT, and compare it to the standard myeloablative conditioning. It is expected there will be therapeutic benefits, paired with better survival rate, less organ toxicity and improved quality of life, following the RIC compared to the myeloablative regimen.
211 studies on the registry are indexed under Primary Immunodeficiency Diseases; 51 are open to participants now.
This study's planned enrollment of 100 is above the median of 36 across 125 interventional studies indexed under Primary Immunodeficiency Diseases.
Browse Primary Immunodeficiency Diseases 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.
Adequate organ function as measured by:
A non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to:
Primary Immunodeficiency syndromes including but not limited to:
Congenital bone marrow failure syndromes including but not limited to:
Inherited Metabolic Disorders (IMD) including but not limited to:
Mucopolysaccharidoses
Leukodystrophies
Other inherited metabolic disorders
Hereditary anemias
Sickle cell disease (SCD) - patients with sickle disease must have one or more of the following:
Inflammatory Conditions
Exclusion:
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.
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.
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.
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.
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).
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 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 condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
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.
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.
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.
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.
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.
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.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
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.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT.
Drug: Hydroxyurea · Drug: Alemtuzumab · Drug: Fludarabine · Drug: Melphalan · Drug: Thiotepa
Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT.
Drug: Hydroxyurea · Drug: Alemtuzumab · Drug: Fludarabine · Drug: Melphalan · Drug: Thiotepa
Oral administration
Also known as: hydroxycarbamide, Hydrea, Droxia
Intravenous (IV) administration.
Also known as: Campath
IV administration
Also known as: Fludara
IV administration
Also known as: Melphalan hydrochloride, Alkeran
IV administration
Post-transplant treatment-related mortality (TRM)
The number of deaths related to the research intervention at day 100, 6 months, and 1 year post-transplant.
Time frame: 1 year post-transplant
Neurodevelopmental milestones
Evaluation of the pace of attaining neurodevelopmental milestones after reduced-intensity conditioning as compared to myeloablative conditioning historical controls from the target population(s).
Time frame: 1 year post-transplant
Immune Reconstitution
Evaluation of the pace of immune reconstitution.
Time frame: 1 year post-transplant
Severe opportunistic infections
Evaluation of the incidence of severe opportunistic infections.
Time frame: 1 year post-transplant
GVHD occurrence
Description of the incidence of acute graft versus host disease (GVHD) (II-IV) and chronic extensive GVHD.
Time frame: 1 year post-transplant
Donor cell engraftment
Determination of the feasibility of attaining robust donor cell engraftment (\>50% donor chimerism at 6 months) following reduced-intensity conditioning (RIC) regimens prior to HSCT in the target population(s).
Time frame: 6 months post-transplant
Normal enzyme level
Determination of the feasibility of attaining and sustaining normal enzyme levels in the target population(s).
Time frame: 1 year post-transplant
Neutrophil recovery
Determination of the pace of neutrophil recovery.
Time frame: 1 year post-transplant
Platelet recovery
Determination of the pace of platelet recovery.
Time frame: 1 year post-transplant
Grade 3-4 organ toxicity
The number of grade 3-4 organ adverse events.
Time frame: 1 year post-transplant
Late graft failure
Evaluation of the incidence of late graft failure.
Time frame: 1 year post-transplant
Plan to share: No
Started Feb 2014 (actual). Primary completion is estimated for Nov 2026, 153 months after the start.
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Studies of the drugs tested here: Hydroxyurea · Alemtuzumab · Fludarabine · Melphalan · Thiotepa
Primary Immunodeficiency Diseases →
Paul Szabolcs