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

NCT04356469 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: HAP-HEMIRB00249753
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Incidence of successful donor engraftment

  The incidence of engraftment at day 100 will be described based on donor chimerism in the whole blood and or fractions sorted for T-cell and myeloid subsets. The donor chimerism will be scored as autologous reconstitution (\< 5% donor), mixed chimerism (5-49%=low mixed, 50-95%=high mixed), \> 95%=full donor chimerism.

  Day 100 after transplantation

Secondary Outcomes (7)

• Overall survival and Event-free survival

  Up to 2 years post transplant

• Kinetics of neutrophil and platelet engraftment

  Up to 42 days post transplant

• Transplant-related mortality

  Up to 100 days post transplant

• Acute grade II-IV GvHD and Chronic GvHD

  Up to 2 years post transplant

• Primary and secondary graft failure

  Up to 2 years post transplant

Study Arms (1)

TCR alpha beta T cell depletion

EXPERIMENTAL

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

Biological: Haploidentical Hematopoietic Cell Transplantation

Interventions

Haploidentical Hematopoietic Cell Transplantation BIOLOGICAL

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

TCR alpha beta T cell depletion

Eligibility Criteria

• Age: 0 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Severe sickle cell disease (HbSS, HbSC, HbSB0, HbSB+, HbSD, HbSE) with at least one of the following criteria:
• Cerebrovascular accident lasting longer than 24 hours
• Impaired neuropsychological function with abnormal brain MRI/MRA
• Patients with frequent (≥ 3 per year for preceding 2 years) painful vaso-occlusive episodes
• Recurrent (≥ 3 in lifetime) acute chest syndrome events which have necessitated erythrocyte transfusion therapy
• 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
• Thalassemia major with at least one of the following criteria:
• Transfusion dependency defined as receiving 8 or more transfusions per year
• 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
• Genotypically proven thalassemia major for children \< 2 years of age even in the absence of transfusion dependency
• 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)
• Bone marrow failure syndromes and autoimmune cytopenias:
• Severe Aplastic Anemia refractory to immunosuppressive therapy
• Diamond Blackfan Anemia refractory to conventional therapy
• Inherited Bone Marrow Failure Syndromes such as Fanconi anemia and Shwachman-Diamond syndrome with progressive marrow failure (without cytogenetic evidence of MDS/AML)

You may not qualify if:

• 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.
• Pregnant or breastfeeding females.
• Patient has HIV or uncontrolled fungal, bacterial or viral infections.
• Patient has received prior solid organ transplant.
• 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.

Sponsors & Collaborators

• Johns Hopkins All Children's Hospital: lead

Study Sites (1)

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

MeSH Terms

Conditions

Hemoglobinopathies; Anemia, Aplastic; Bone Marrow Failure Disorders

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia; Bone Marrow Diseases

Study Officials

• Deepak Chellapandian, MD

  Johns Hopkins All Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jade Hanson, MSN

CONTACT

7277676468; jade.hanson@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2020
• First Posted: April 22, 2020
• Study Start: July 22, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)