Congenital Bone Marrow Failure Syndromes · Hereditary Anemias · Inflammatory Conditions · Inherited Metabolic Disorders (IMD) · Juvenile Rheumatoid Arthritis (JRA) · Primary Immunodeficiency (PID) · Systemic Juvenile Idiopathic Arthritis (sJIA)
Reduced-intensity conditioning before stem cell transplant for noncancer disorders
This phase 2 study is evaluating reduced-intensity conditioning before donor stem cell transplantation in people ages 2 months to 55 years with eligible noncancer disorders, with follow-up for transplant outcomes and late effects.
Registry title: Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT
1 recruiting U.S. site ↓Study at a glance
- Age
- 2 Months–55 Years
- Treatment
- Hydroxyurea or Alemtuzumab
- Design
- Non Randomized
- Central study contact
- Paul Szabolcs, MD412-692-5427paul.szabolcs@chp.edu
- Sponsor
- Paul Szabolcs
Research question
What transplant outcomes occur when people with eligible noncancer disorders receive reduced-intensity conditioning before donor stem cell transplantation, compared with historical experience using standard myeloablative conditioning?
Participant snapshot
Who the study is looking for
- The study is looking for people ages 2 months through 55 years.
- The study is looking for people with a noncancer disorder considered amenable to stem cell transplantation.
- Listed disorder groups include primary immune deficiencies, congenital bone marrow failure, inherited metabolic disorders, hereditary anemias, and inflammatory conditions such as Crohn's disease or inflammatory bowel disease.
- The study requires a suitably matched cord-blood, bone-marrow, or peripheral-blood stem-cell graft meeting the registry's matching and cell-dose rules.
- The registry lists one recruiting location at UPMC Children's Hospital of Pittsburgh in Pennsylvania.
Participation overview
What participation may involve
Participants receive a reduced-intensity conditioning regimen containing oral hydroxyurea and intravenous alemtuzumab, fludarabine, melphalan, and thiotepa before an allogeneic cord-blood, bone-marrow, or peripheral-blood stem cell transplant, followed by assessment of transplant outcomes and late effects. What participation may involve: - Receive hydroxyurea by mouth and alemtuzumab, fludarabine, melphalan, and thiotepa intravenously as pre-transplant conditioning. - Undergo allogeneic hematopoietic stem cell transplantation using eligible cord blood, bone marrow, or peripheral-blood stem cells. - Be followed after transplant for treatment-related mortality, neurodevelopment, immune recovery, severe opportunistic infections, graft-versus-host disease, engraftment, blood-cell recovery, organ toxicity, graft failure, and other applicable outcomes.
Study interventions
What participants may receive or do
- Hydroxyurea: Hydroxyurea is given by mouth as part of the conditioning regimen before allogeneic hematopoietic stem cell transplantation.
- Alemtuzumab: Alemtuzumab is given intravenously as part of the conditioning regimen before allogeneic hematopoietic stem cell transplantation.
- Fludarabine: Fludarabine is given intravenously as part of the conditioning regimen before allogeneic hematopoietic stem cell transplantation.
- Melphalan: Melphalan is given intravenously as part of the conditioning regimen before allogeneic hematopoietic stem cell transplantation.
- Thiotepa: Thiotepa is given intravenously as part of the conditioning regimen before allogeneic hematopoietic stem cell transplantation.
Study design
How the comparison works
This is an open-label, nonrandomized phase 2 treatment study with two parallel experimental groups based on graft and disease-related characteristics. Both groups receive the listed reduced-intensity conditioning drugs before donor stem cell transplantation. Assignment is nonrandomized, so participants are not assigned to the study groups by chance. The study uses no masking, meaning treatment assignment is not blinded. The registry does not list a concurrent control arm; the detailed description says study data will be compared with historical controls who received standard myeloablative conditioning.
Reported activities
Procedures and tests
- Screening requires confirmation that a suitably matched donor graft meeting the applicable cord-blood cell-dose or marrow/peripheral-blood matching rules is available.
- Kidney screening includes creatinine and creatinine-clearance measurements.
- Liver screening includes alanine and aspartate transaminase blood tests.
- Cardiac function must be assessed by echocardiogram or radionuclide scan.
- Pulmonary screening may include lung-function testing, resting pulse oximetry, diffusing capacity testing for adults when obtainable, or pulmonologist clearance.
- Pubertal or menstruating participants must have a negative pregnancy test.
- Screening requires a negative human immunodeficiency virus test.
- Post-transplant assessments include donor-cell engraftment or chimerism and neutrophil and platelet recovery.
- Follow-up includes assessment of immune reconstitution and severe opportunistic infections.
- Follow-up includes assessment for acute and chronic graft-versus-host disease, organ toxicity, and late graft failure.
- Neurodevelopmental milestones are evaluated after reduced-intensity conditioning.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- A qualifying donor graft must be available: a 4/6, 5/6, or 6/6 HLA-matched cord-blood unit meeting the stated cell dose; qualifying double cord units; or a 7/8 or 8/8 allele-matched unrelated bone-marrow or peripheral-blood graft.
- Kidney function must meet both thresholds: creatinine no greater than 2.0 mg/dL and creatinine clearance at least 50 mL/min/1.73 m².
- Alanine and aspartate transaminase liver-test results must be no more than four times the upper limit of normal.
- Cardiac testing must show a shortening fraction above 26%, an ejection fraction above 40%, or a value above 80% of normal for age.
- Pulmonary eligibility requires the stated lung-function or oxygen threshold, or clearance by a pediatric or adult pulmonologist; adults should also meet the diffusing-capacity threshold when that test can be obtained.
- The person must have a noncancer disorder considered amenable to stem cell transplantation, within the listed groups or another disorder accepted under the criterion.
- For sickle cell disease, at least one listed complication is required: overt or silent stroke, at least two pain crises in the past year, acute chest syndrome, osteonecrosis in at least one joint, or priapism.
- Written informed consent and, when applicable, assent are required according to U.S. Food and Drug Administration guidelines.
- A negative pregnancy test is required for participants who are pubertal or menstruating.
- A negative human immunodeficiency virus test is required.
Possible reasons someone may not be able to join
- A previous allogeneic hematopoietic stem cell transplant within the past six months excludes participation.
- Any active cancer or myelodysplastic syndrome excludes participation.
- Severe acquired aplastic anemia excludes participation.
- An uncontrolled bacterial, viral, or fungal infection excludes participation when it is being treated and clinical symptoms are progressing.
- Pregnant people and nursing mothers are excluded.
- Poorly controlled pulmonary hypertension excludes participation.
- Any condition that prevents serial follow-up excludes participation.
Important unknowns
What the record does not make clear
- The registry does not state how many study visits are required or when they occur.
- Several outcomes are measured through one year after transplant, and the registry says participants will be followed for late effects, but it does not state the total participation duration.
- The registry does not explain which current disease treatments can continue before, during, or after conditioning and transplant.
- No medication washout requirements or timing rules are reported.
- The registry does not describe rescue treatment or management plans for graft failure, severe infection, graft-versus-host disease, or other complications.
- The record says research funds are not available to assist with enrollment but does not identify which transplant, study, or follow-up costs are billed to participants or insurance.
- The registry does not report whether participants are compensated.
- The record says research funds are not available to assist with enrollment, but it does not specifically explain whether travel or lodging support is available from another source.
- The registry does not state whether any follow-up assessments can be completed remotely or with a local clinician.
- The registry does not describe access to study-related care or monitoring after study follow-up ends.
- The registry lists two experimental groups and no placebo intervention, but it does not explicitly state that placebo use is excluded.
Before contacting the site
Questions for the study team
- What is the full conditioning, transplant, hospitalization, and follow-up schedule?
- How do you decide which graft-based study group applies, and does that choice change the conditioning regimen or monitoring?
- Which current medicines and supportive treatments may continue, and are any washout periods required?
- What plans are used to prevent and manage infection, graft-versus-host disease, organ toxicity, or graft failure?
- Which costs are covered, and is any assistance available for travel, lodging, meals, or parking?
- Can any follow-up be coordinated with clinicians near home, and what long-term care is available after study follow-up ends?
Before changing care
Questions for your gastroenterologist
- How stable is the gastrointestinal or inflammatory disease now, and how might that affect the risks of conditioning and stem cell transplantation?
- Would any current gastrointestinal medicines need to change before transplant, and how could treatment continuity be protected?
- What approved or standard treatment alternatives should be considered before discussing this transplant study further?
- How should my gastroenterology team and the transplant research team coordinate medication decisions, infection monitoring, nutrition, and follow-up?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
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.
Study design and administration
- Organization
- University of Pittsburgh
- Organization class
- Other
- Organization study ID
- STUDY19060337
- Lead sponsor
- Paul Szabolcs
- Sponsor class
- Other
- Enrollment type
- Estimated
- Allocation
- Non Randomized
- Intervention model
- Parallel
- Primary purpose
- Treatment
- Masking
- None
- Who is masked
- Not provided
- Standard age groups
- Child, Adult
Study arms
Experimental
UCBT:transfusion dependent anemias or increased rejection risk
Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT.
Interventions: Drug: Hydroxyurea, Drug: Alemtuzumab, Drug: Fludarabine, Drug: Melphalan, Drug: Thiotepa
Experimental
BMT, PBSCT and not transfusion dependent UCBT
Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT.
Interventions: Drug: Hydroxyurea, Drug: Alemtuzumab, Drug: Fludarabine, Drug: Melphalan, Drug: Thiotepa
Interventions
Drug
Hydroxyurea
Oral administration
Drug
Alemtuzumab
Intravenous (IV) administration.
Drug
Fludarabine
IV administration
Drug
Melphalan
IV administration
Drug
Thiotepa
IV administration
Eligibility
2 Months–55 Years
All
Not accepted
Inclusion criteria (55)
- 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.Registry-derived · unreviewed
- Adequate organ function as measured by:Registry-derived · unreviewed
- Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥ 50 mL/min/1.73 m2.Registry-derived · unreviewed
- Hepatic transaminases (ALT/AST) ≤ 4 x upper limit of normal (ULN).Registry-derived · unreviewed
- Adequate cardiac function by echocardiogram or radionuclide scan (shortening fraction \> 26% or ejection fraction \> 40% or \> 80% of normal value for age).Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- Written informed consent and/or assent according to FDA guidelines.Registry-derived · unreviewed
- Negative pregnancy test if pubertal and/or menstruating.Registry-derived · unreviewed
- HIV negative.Registry-derived · unreviewed
- A non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to:Registry-derived · unreviewed
- Primary Immunodeficiency syndromes including but not limited to:Registry-derived · unreviewed
- Severe Combined Immune Deficiency (SCID) with NK cell activityRegistry-derived · unreviewed
- Omenn SyndromeRegistry-derived · unreviewed
- Bare Lymphocyte Syndrome (BLS)Registry-derived · unreviewed
- Combined Immune Deficiency (CID) syndromesRegistry-derived · unreviewed
- Combined Variable Immune Deficiency (CVID) syndromeRegistry-derived · unreviewed
- Wiskott-Aldrich SyndromeRegistry-derived · unreviewed
- Leukocyte adhesion deficiencyRegistry-derived · unreviewed
- Chronic granulomatous disease (CGD)Registry-derived · unreviewed
- X-linked Hyper IgM (XHIM) syndromeRegistry-derived · unreviewed
- IPEX syndromeRegistry-derived · unreviewed
- Chediak - Higashi SyndromeRegistry-derived · unreviewed
- Autoimmune Lymphoproliferative Syndrome (ALPS)Registry-derived · unreviewed
- Hemophagocytic Lymphohistiocytosis (HLH) syndromesRegistry-derived · unreviewed
- Lymphocyte Signaling defectsRegistry-derived · unreviewed
- Other primary immune defects where hematopoietic stem cell transplantation may be beneficialRegistry-derived · unreviewed
- Congenital bone marrow failure syndromes including but not limited to:Registry-derived · unreviewed
- Dyskeratosis Congenita (DC)Registry-derived · unreviewed
- Congenital Amegakaryocytic Thrombocytopenia (CAMT)Registry-derived · unreviewed
- OsteopetrosisRegistry-derived · unreviewed
- Inherited Metabolic Disorders (IMD) including but not limited to:Registry-derived · unreviewed
- MucopolysaccharidosesRegistry-derived · unreviewed
- Hurler syndrome (MPS I)Registry-derived · unreviewed
- Hunter syndrome (MPS II)Registry-derived · unreviewed
- LeukodystrophiesRegistry-derived · unreviewed
- Krabbe Disease, also known as globoid cell leukodystrophyRegistry-derived · unreviewed
- Metachromatic leukodystrophy (MLD)Registry-derived · unreviewed
- X-linked adrenoleukodystrophy (ALD)Registry-derived · unreviewed
- Hereditary diffuse leukoencephalopathy with spheroids (HDLS)Registry-derived · unreviewed
- Other inherited metabolic disordersRegistry-derived · unreviewed
- alpha mannosidosisRegistry-derived · unreviewed
- Gaucher DiseaseRegistry-derived · unreviewed
- Other inheritable metabolic diseases where hematopoietic stem cell transplantation may be beneficial.Registry-derived · unreviewed
- Hereditary anemiasRegistry-derived · unreviewed
- Thalassemia majorRegistry-derived · unreviewed
- Sickle cell disease (SCD) - patients with sickle disease must have one or more of the following:Registry-derived · unreviewed
- Overt or silent strokeRegistry-derived · unreviewed
- Pain crises ≥ 2 episodes per year for past yearRegistry-derived · unreviewed
- One or more episodes of acute chest syndromeRegistry-derived · unreviewed
- Osteonecrosis involving ≥ 1 jointsRegistry-derived · unreviewed
- PriapismRegistry-derived · unreviewed
- Diamond Blackfan Anemia (DBA)Registry-derived · unreviewed
- Other congenital transfusion dependent anemiasRegistry-derived · unreviewed
- Inflammatory ConditionsRegistry-derived · unreviewed
- Crohn's Disease/Inflammatory Bowel DiseaseRegistry-derived · unreviewed
Exclusion criteria (7)
- Allogeneic hematopoietic stem cell transplant within the previous 6 months.Registry-derived · unreviewed
- Any active malignancy or MDS.Registry-derived · unreviewed
- Severe acquired aplastic anemia.Registry-derived · unreviewed
- Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression of clinical symptoms).Registry-derived · unreviewed
- Pregnancy or nursing mother.Registry-derived · unreviewed
- Poorly controlled pulmonary hypertension.Registry-derived · unreviewed
- Any condition that precludes serial follow-up.Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Post-transplant treatment-related mortality (TRM)
Time frame: 1 year post-transplant
The number of deaths related to the research intervention at day 100, 6 months, and 1 year post-transplant.
Primary outcome
Neurodevelopmental milestones
Time frame: 1 year post-transplant
Evaluation of the pace of attaining neurodevelopmental milestones after reduced-intensity conditioning as compared to myeloablative conditioning historical controls from the target population(s).
Primary outcome
Immune Reconstitution
Time frame: 1 year post-transplant
Evaluation of the pace of immune reconstitution.
Primary outcome
Severe opportunistic infections
Time frame: 1 year post-transplant
Evaluation of the incidence of severe opportunistic infections.
Primary outcome
GVHD occurrence
Time frame: 1 year post-transplant
Description of the incidence of acute graft versus host disease (GVHD) (II-IV) and chronic extensive GVHD.
Secondary outcome
Donor cell engraftment
Time frame: 6 months post-transplant
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).
Secondary outcome
Normal enzyme level
Time frame: 1 year post-transplant
Determination of the feasibility of attaining and sustaining normal enzyme levels in the target population(s).
Secondary outcome
Neutrophil recovery
Time frame: 1 year post-transplant
Determination of the pace of neutrophil recovery.
Secondary outcome
Platelet recovery
Time frame: 1 year post-transplant
Determination of the pace of platelet recovery.
Secondary outcome
Grade 3-4 organ toxicity
Time frame: 1 year post-transplant
The number of grade 3-4 organ adverse events.
Secondary outcome
Late graft failure
Time frame: 1 year post-transplant
Evaluation of the incidence of late graft failure.
Recruiting locations in the United States
UPMC Children's Hospital of Pittsburgh
RecruitingPittsburgh, Pennsylvania, 15224, United States
Shawna McIntyre, RN412-692-5552mcintyresm@upmc.edu
Paulina Horvei, MD
Randy Windreich, MD
Archana Ramgopal, DO
Central study contacts
Registry dates
- First posted
- Oct 14, 2013
- Primary completion
- Nov 2026
- Overall completion
- Nov 2027
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.