Haploidentical stem cell transplant for treating blood disorders in children

Study of TCR Alpha Beta T-Cell and CD19 B-Cell Depletion for Hematopoietic Cell Transplantation From Haploidentical Donors in the Treatment of Non-Malignant Hematological Disorders in Children

This study is testing a new way to use stem cell transplants from partially matched family members to help children with serious blood disorders feel better when other treatments haven't worked.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 17 (estimated)
• Ages: 0 Years to 21 Years
• Sex: All
• Sponsor: Johns Hopkins All Children's Hospital (Academic / other)
• Locations: 1 site (St. Petersburg, Florida)
• Trial ID: NCT04356469 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and effectiveness of a new haploidentical transplantation method using TCR alpha beta and CD19 depleted stem cell grafts from half-matched family donors. The stem cells will be collected from either peripheral blood or bone marrow and processed using an investigational device called CliniMACS. The focus is on treating severe hematological conditions in children, such as hemoglobinopathy and severe aplastic anemia. The trial aims to provide a novel approach to transplantation for patients who have not responded to conventional therapies.

Who should consider this trial

Good fit: Ideal candidates include children with severe sickle cell disease or thalassemia major who meet specific clinical criteria.

Not a fit: Patients with non-hematological disorders or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could offer a new treatment option for children with severe blood disorders who currently have limited options.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in the field of haploidentical transplantation, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Severe sickle cell disease (HbSS, HbSC, HbSB0, HbSB+, HbSD, HbSE) with at least one of the following criteria:

   1. Cerebrovascular accident lasting longer than 24 hours
   2. Impaired neuropsychological function with abnormal brain MRI/MRA
   3. Patients with frequent (≥ 3 per year for preceding 2 years) painful vaso-occlusive episodes
   4. Recurrent (≥ 3 in lifetime) acute chest syndrome events which have necessitated erythrocyte transfusion therapy
   5. Any combination of ≥ 3 acute chest syndrome episodes and vaso-occlusive pain episodes yearly for 3 years and have failed treatment with hydroxyurea (HU) (at least 6 months on maximum tolerated dose) or who are intolerant to HU therapy
2. Thalassemia major with at least one of the following criteria:

   1. Transfusion dependency defined as receiving 8 or more transfusions per year
   2. Thalassemia diagnosis documented by clinical assessment, laboratory evidence with microcytic anemia and absence of HbA (\< 10%) on electrophoresis and or confirmation by DNA analysis of alpha and beta gene loci
   3. Genotypically proven thalassemia major for children \< 2 years of age even in the absence of transfusion dependency
   4. Lucarelli class 1 or 2 risk status (i.e. with only 0-2 of the following factors: hepatomegaly, portal fibrosis, or poor response to chelation therapy)
3. Bone marrow failure syndromes and autoimmune cytopenias:

   1. Severe Aplastic Anemia refractory to immunosuppressive therapy
   2. Diamond Blackfan Anemia refractory to conventional therapy
   3. Inherited Bone Marrow Failure Syndromes such as Fanconi anemia and Shwachman-Diamond syndrome with progressive marrow failure (without cytogenetic evidence of MDS/AML)
   4. Severe Congenital Neutropenia
   5. Congenital Amegakaryocytic Thrombocytopenia
   6. Glanzmann Thrombasthenia
   7. Autoimmune Cytopenias refractory to conventional treatment (including Pure red cell aplasia, Evan's syndrome, Immune thrombocytopenia, autoimmune hemolytic anemia)
   8. Other marrow failure disorders not otherwise specified

Inclusion Criteria:

1. Patient has a suitable genotypic identical match of 5/10. The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1.
2. Patients must have adequate organ function measured by:

   1. Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 40% or SF ≥ 26%
   2. Pulmonary: asymptomatic or if symptomatic DLCO ≥ 40% of predicted (corrected for hemoglobin) or pulse oximetry ≥ 92% on room air if the patient is unable to perform pulmonary function testing.
   3. Renal: Creatinine clearance (CrCl) or glomerular filtration rate (GFR) must be \> 50 mL/min/1.73 m2.
   4. Hepatic: Serum conjugated (direct) bilirubin \< 2.0 x ULN for age as per local laboratory unless attributable to Gilbert's syndrome; AST and ALT \< 5.0 x ULN for age as per local laboratory. Patients with hyperbilirubinemia as a consequence of hyperhemolysis, or a profound change in serum hemoglobin post blood transfusion, are not excluded.
   5. Karnofsky or Lansky (age-dependent) performance score ≥ 50
3. Signed written informed consent

Exclusion Criteria:

1. Participants who have an HLA-matched sibling who is able and willing to donate bone marrow. Patients with a HLA-matched unrelated donors are not excluded.
2. Pregnant or breastfeeding females.
3. Patient has HIV or uncontrolled fungal, bacterial or viral infections.
4. Patient has received prior solid organ transplant.
5. Patient has active GVHD (\> grade II) or chronic extensive GVHD due to a previous allograft at the time of inclusion.
6. For patients with hemoglobinopathy, liver biopsy is necessary if the patient has received chronic transfusions for over a year and has two ferritin levels of ≥ 1000 ng/ml. Patients with cirrhosis, extensive bridging hepatic fibrosis, or active hepatitis are excluded from enrollment.

Where this trial is running

St. Petersburg, Florida

• Johns Hopkins All Children's Hospital — St. Petersburg, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Deepak Chellapandian, MD — Johns Hopkins All Children's Hospital
• Study coordinator: Jade Hanson, MSN

Conditions Hemoglobinopathy; Severe Aplastic Anemia; Bone Marrow Failure Syndrome