ClinicalTrials.gov record NCT01962415

Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

A Phase II Study of Reduced Intensity Conditioning in Pediatric Patients and Young Adults ≤55 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplantation

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 2A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
Age2 months old to 55 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This Phase II interventional study evaluates a reduced-intensity chemotherapy conditioning regimen given before allogeneic hematopoietic stem cell transplant (umbilical cord blood, bone marrow, or peripheral blood) in patients up to 55 years with non-malignant disorders. Participants receive a lower-dose conditioning drug combination prior to transplant and are followed for graft success, transplant-related mortality, immune recovery, infections, graft-versus-host disease, and neurodevelopment. The study compares these outcomes to historical myeloablative conditioning data.

What it is studying. The study tests a reduced-intensity conditioning (lower doses of chemotherapy and immune-depleting drugs) used before allogeneic stem cell transplant to see how well donor stem cells engraft and how patients fare afterward. It will collect data on transplant-related deaths, timing of immune and blood-count recovery, severe opportunistic infections, acute and chronic graft-versus-host disease, neurodevelopmental milestones, donor chimerism, enzyme levels where relevant, organ toxicities, and late graft failure, compared to standard myeloablative conditioning outcomes from historic data.

What the researchers hope to learn. Scientific goals: measure transplant-related mortality at day 100, 6 months, and 1 year; assess neurodevelopmental milestone attainment; evaluate pace of immune reconstitution; record incidence of severe opportunistic infections; describe acute (II-IV) and chronic extensive graft-versus-host disease; determine feasibility of attaining >50% donor chimerism at 6 months; assess normalization of enzyme levels where applicable; track neutrophil and platelet recovery; count grade 3–4 organ toxicities; and evaluate late graft failure.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Hydroxyurea
  • Alemtuzumab
  • Fludarabine
  • Melphalan
  • Thiotepa

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Inclusion:
  • A 4/6, 5/6 or 6/6 HLA matched related or unrelated UCB unit available that will deliver a pre-cryopreservation total nucleated cell dose of ≥ 3 x 10e7 cells/kg, or double unit grafts, each cord blood unit delivering at least 2 x 10e7 cells/kg OR an 8 of 8 or 7 of 8 HLA allele level matched unrelated donor bone marrow or peripheral blood progenitor graft.
  • Adequate organ function as measured by:
  • Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥ 50 mL/min/1.73 m2.
  • Hepatic transaminases (ALT/AST) ≤ 4 x upper limit of normal (ULN).
  • Adequate cardiac function by echocardiogram or radionuclide scan (shortening fraction > 26% or ejection fraction > 40% or > 80% of normal value for age).
  • Pulmonary evaluation testing demonstrating CVC or FEV1/FVC of ≥ 50% of predicted for age and/or resting pulse oximeter ≥ 92% on room air or clearance by the pediatric or adult pulmonologist. For adult patients DLCO (corrected for hemoglobin) should be ≥ 50% of predicted if the DLCO can be obtained.
  • Written informed consent and/or assent according to FDA guidelines.
  • Negative pregnancy test if pubertal and/or menstruating.
  • HIV negative.
  • A non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to:
  • Primary Immunodeficiency syndromes including but not limited to:
  • Severe Combined Immune Deficiency (SCID) with NK cell activity
  • Omenn Syndrome
  • Bare Lymphocyte Syndrome (BLS)
  • Combined Immune Deficiency (CID) syndromes
  • Combined Variable Immune Deficiency (CVID) syndrome
  • Wiskott-Aldrich Syndrome
  • Leukocyte adhesion deficiency
  • Chronic granulomatous disease (CGD)
  • X-linked Hyper IgM (XHIM) syndrome
  • IPEX syndrome
  • Chediak - Higashi Syndrome
  • Autoimmune Lymphoproliferative Syndrome (ALPS)
  • Hemophagocytic Lymphohistiocytosis (HLH) syndromes
  • Lymphocyte Signaling defects
  • Other primary immune defects where hematopoietic stem cell transplantation may be beneficial
  • Congenital bone marrow failure syndromes including but not limited to:
  • Dyskeratosis Congenita (DC)
  • Congenital Amegakaryocytic Thrombocytopenia (CAMT)
  • Osteopetrosis
  • Inherited Metabolic Disorders (IMD) including but not limited to:
  • Mucopolysaccharidoses
  • Hurler syndrome (MPS I)
  • Hunter syndrome (MPS II)
  • Leukodystrophies
  • Krabbe Disease, also known as globoid cell leukodystrophy
  • Metachromatic leukodystrophy (MLD)
  • X-linked adrenoleukodystrophy (ALD)
  • Hereditary diffuse leukoencephalopathy with spheroids (HDLS)
  • Other inherited metabolic disorders
  • alpha mannosidosis
  • Gaucher Disease
  • Other inheritable metabolic diseases where hematopoietic stem cell transplantation may be beneficial.
  • Hereditary anemias
  • Thalassemia major
  • Sickle cell disease (SCD) - patients with sickle disease must have one or more of the following:
  • Overt or silent stroke
  • Pain crises ≥ 2 episodes per year for past year
  • One or more episodes of acute chest syndrome
  • Osteonecrosis involving ≥ 1 joints
  • Priapism
  • Diamond Blackfan Anemia (DBA)
  • Other congenital transfusion dependent anemias
  • Inflammatory Conditions
  • Crohn's Disease/Inflammatory Bowel Disease
  • Exclusion:
  • Allogeneic hematopoietic stem cell transplant within the previous 6 months.
  • Any active malignancy or MDS.
  • Severe acquired aplastic anemia.
  • Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression of clinical symptoms).
  • Pregnancy or nursing mother.
  • Poorly controlled pulmonary hypertension.
  • Any condition that precludes serial follow-up.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

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.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants receive a reduced‑intensity conditioning regimen of drugs (including alemtuzumab IV, fludarabine IV, melphalan IV, thiotepa IV and oral hydroxyurea) prior to an allogeneic stem‑cell transplant (single or double umbilical cord blood, matched unrelated bone marrow, or peripheral blood stem cells). After transplant they attend regular follow‑up visits and testing to monitor outcomes such as treatment‑related mortality, donor engraftment (including a 6‑month chimerism check), immune recovery, infections, graft‑versus‑host disease, organ toxicity, blood‑count recovery, and neurodevelopmental milestones in children. Follow‑up assessments are planned through at least one year post‑transplant. The registry does not provide a detailed schedule of visits or information about financial support for enrollment.

How the study is structured. Phase II, interventional, non-randomized with parallel experimental arms. No masking. Participants receive a specified reduced-intensity drug regimen (including alemtuzumab, hydroxyurea, fludarabine, melphalan, and thiotepa) before an allogeneic hematopoietic stem cell transplant using single or double cord blood units, matched unrelated bone marrow, or peripheral blood stem cell grafts. Outcomes are tracked after transplant, with key measures at 6 months and 1 year.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on Hunter syndrome

This trial is also listed on this site under alpha-mannosidosis, Gaucher disease, hemophagocytic lymphohistiocytosis, Hurler syndrome, Krabbe disease and metachromatic leukodystrophy.

Clinical trials10 trials listed for Hunter syndromeEvery trial the registry lists for Hunter syndrome, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Hunter syndrome researchLatest monthly update: September 2026. Includes: Brain-targeted enzyme. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Feb 4, 2014
Primary completion
November 2026 (estimated)
Study completion
November 2027 (estimated)
Target enrollment
100 participants (estimated)
Last updated on registry
Dec 15, 2025
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Paul Szabolcs

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

  • UPMC Children's Hospital of PittsburghRecruiting

    Pittsburgh, Pennsylvania, 15224 · United States

Terms used on this page · explanations by MedicalUpdates.ai

bone marrow transplant
A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
creatinine clearance
A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
upper limit of normal
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
echocardiogram
An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
FVC
A breathing test that measures the total amount of air a person can blow out after a full breath in. It is often given as a percentage of what is expected for a person's age and size.
DLCO
A breathing test that measures how well the lungs pass oxygen from the air into the blood.
Written informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
assent
A child's or dependent adult's agreement to take part, given alongside the formal consent of a parent or legal representative.
follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
enrollment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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