TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Non-Malignant Hematological Disorders in Children

NCT ID: NCT04356469

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-22
• Study Completion Date: 2026-06-30

Brief Summary

This research is being done to learn if a new type of haploidentical transplantation using TCR alpha beta and CD19 depleted stem cell graft from the donor is safe and effective to treat the patient's underlying condition. This study will use stem cells obtained via peripheral blood or bone marrow from parent or other half-matched family member donor. These will be processed through a special device called CliniMACS, which is considered investigational.

Conditions

Hemoglobinopathy (Disorder); Severe Aplastic Anemia; Bone Marrow Failure Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TCR alpha beta T cell depletion

The leukapheresis product will undergo TCR alpha beta negative selection following a standardized protocol

Group Type: EXPERIMENTAL

Haploidentical Hematopoietic Cell Transplantation

Intervention Type: BIOLOGICAL

TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation

Interventions

Haploidentical Hematopoietic Cell Transplantation

TCR alpha beta T-cell and CD19 B-cell depleted haploidentical transplantation

Intervention Type: BIOLOGICAL

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

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.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins All Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Deepak Chellapandian, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins All Children's Hospital

Locations

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jade Hanson, MSN

Role: CONTACT

jade.hanson@jhmi.edu

7277676468

Facility Contacts

Ian Snyder

Role: primary

isnyder5@jhmi.edu

Other Identifiers

IRB00249753

Identifier Type: OTHER

Identifier Source: secondary_id

HAP-HEM

Identifier Type: -

Identifier Source: org_study_id