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

• Register: ClinicalTrials.gov
• Last refreshed on: 8 April 2024
• Main ID: NCT01962415
• Date of registration: 10/10/2013
• Prospective Registration: Yes
• Primary sponsor: Paul Szabolcs
• Public title: Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT HSCT+RIC
• Scientific title: 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
• Date of first enrolment: February 4, 2014
• Target sample size: 100
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01962415
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Paul Szabolcs, MD
• Affiliation: University of Pittsburgh

• Name: Shawna McIntyre, RN

• Name: Paul Szabolcs, MD

Key inclusion & exclusion 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.



Age minimum: 2 Months
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Inherited Metabolic Disorders (IMD)

Inflammatory Conditions

Systemic Juvenile Idiopathic Arthritis (sJIA)

Congenital Bone Marrow Failure Syndromes

Hereditary Anemias

Primary Immunodeficiency (PID)

Intervention(s)

Drug: Fludarabine

Drug: Hydroxyurea

Drug: Alemtuzumab

Drug: Thiotepa

Drug: Melphalan

Primary Outcome(s)

Post-transplant treatment-related mortality (TRM) [Time Frame: 1 year post-transplant]

GVHD occurrence [Time Frame: 1 year post-transplant]

Severe opportunistic infections [Time Frame: 1 year post-transplant]

Immune Reconstitution [Time Frame: 1 year post-transplant]

Neurodevelopmental milestones [Time Frame: 1 year post-transplant]

Secondary Outcome(s)

Platelet recovery [Time Frame: 1 year post-transplant]

Donor cell engraftment [Time Frame: 6 months post-transplant]

Neutrophil recovery [Time Frame: 1 year post-transplant]

Late graft failure [Time Frame: 1 year post-transplant]

Normal enzyme level [Time Frame: 1 year post-transplant]

Grade 3-4 organ toxicity [Time Frame: 1 year post-transplant]

Secondary ID(s)

PRO13100018

Source(s) of Monetary Support

Please refer to primary and secondary sponsors