Reduced intensity conditioning for patients with non-malignant disorders undergoing stem cell transplants

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

This study is testing a gentler approach to stem cell transplants for people with non-cancerous disorders to see if it helps them recover better with fewer risks.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 2 Months to 55 Years
• Sex: All
• Sponsor: University of Pittsburgh (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT01962415 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy of a reduced-intensity conditioning (RIC) regimen combined 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. The approach aims to use lower doses of chemotherapy to facilitate engraftment while minimizing transplant-related mortality. Participants will be monitored for late effects and ongoing graft success post-transplant. The study focuses on conditions such as primary immunodeficiency and inherited metabolic disorders, where traditional high-intensity conditioning may pose risks.

Who should consider this trial

Good fit: Ideal candidates include patients with primary immunodeficiency, congenital bone marrow failure syndromes, or other inherited metabolic disorders who meet specific HLA matching criteria.

Not a fit: Patients with malignant disorders or those who do not meet the eligibility criteria for HLA matching or organ function may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve transplant outcomes and reduce complications for patients with non-malignant disorders.

How similar studies have performed: Other studies have shown promise with reduced-intensity conditioning in similar patient populations, suggesting potential for success in this approach.

Eligibility criteria

Inclusion:

1. 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.
2. Adequate organ function as measured by:

   1. Creatinine ≤ 2.0 mg/dL and creatinine clearance ≥ 50 mL/min/1.73 m2.
   2. Hepatic transaminases (ALT/AST) ≤ 4 x upper limit of normal (ULN).
   3. Adequate cardiac function by echocardiogram or radionuclide scan (shortening fraction \> 26% or ejection fraction \> 40% or \> 80% of normal value for age).
   4. 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.
3. Written informed consent and/or assent according to FDA guidelines.
4. Negative pregnancy test if pubertal and/or menstruating.
5. HIV negative.
6. A non-malignant disorder amenable to treatment by stem cell transplantation, including but not limited to:

   1. 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
   2. Congenital bone marrow failure syndromes including but not limited to:

      * Dyskeratosis Congenita (DC)
      * Congenital Amegakaryocytic Thrombocytopenia (CAMT)
      * Osteopetrosis
   3. 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.
   4. 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
   5. Inflammatory Conditions

      * Crohn's Disease/Inflammatory Bowel Disease

Exclusion:

1. Allogeneic hematopoietic stem cell transplant within the previous 6 months.
2. Any active malignancy or MDS.
3. Severe acquired aplastic anemia.
4. Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression of clinical symptoms).
5. Pregnancy or nursing mother.
6. Poorly controlled pulmonary hypertension.
7. Any condition that precludes serial follow-up.

Where this trial is running

Pittsburgh, Pennsylvania

• UPMC Children's Hospital of Pittsburgh — Pittsburgh, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Paul Szabolcs, MD — University of Pittsburgh
• Study coordinator: Paul Szabolcs, MD

Conditions: Primary Immunodeficiency, Congenital Bone Marrow Failure Syndromes, Inherited Metabolic Disorders, Hereditary Anemias, Inflammatory Conditions, Systemic Juvenile Idiopathic Arthritis, Juvenile Rheumatoid Arthritis, Severe Combined Immune Deficiency