Haploidentical Hematopoietic Cell Transplantation for Children With Hematologic Malignancies and Myelodysplasia

NCT ID: NCT03431090

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-02
• Study Completion Date: 2026-01-31

Brief Summary

This is a Phase I/II study designed to evaluate the kinetics of hematopoietic reconstitution and the incidence of acute chronic GVHD after partially matched related donor hematopoietic cell transplantation using an αβTCR/CD19+ cell depleted graft.

Detailed Description

Less than 30% of patients undergoing hematopoietic cell transplantation (HCT) will have an HLA-matched sibling donor. There is a high likelihood of being unable to identify a perfect HLA matched unrelated donor, and the time to procure the marrow if such a donor is available is generally >3 months. An emerging body of literature suggests that related haploidentical HCT with innovative graft engineering may provide equal, or possibly superior, outcomes to conventional unrelated donors. This protocol is designed to test the hypothesis that HCT using an αβT cell / CD19+ B cell depleted graft from partially matched related donors will result in rapid, durable hematopoietic engraftment and rapid immune reconstitution with an acceptably low risk of severe acute and chronic GVHD.

Conditions

Myelodysplasia; Hematologic Malignancy

Study Design

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

Study Groups

CliniMACS Isolation

The mobilized peripheral blood cell collection (apheresis product) will be processed using a Miltenyi CliniMACS device according to the manufacturing instructions. The processing will deplete the αβTCR+ cells and CD19+ cells from the apheresis product to formulate the graft.

Group Type: EXPERIMENTAL

CliniMACS® TCRαβ/CD19 Combined Depletion System

Intervention Type: DEVICE

The mobilized peripheral blood cell collection (apheresis product) will be processed using a Miltenyi CliniMACS device according to the manufacturing instructions. The processing will deplete the αβTCR+ cells and CD19+ cells from the apheresis product to formulate the graft.

Interventions

CliniMACS® TCRαβ/CD19 Combined Depletion System

The mobilized peripheral blood cell collection (apheresis product) will be processed using a Miltenyi CliniMACS device according to the manufacturing instructions. The processing will deplete the αβTCR+ cells and CD19+ cells from the apheresis product to formulate the graft.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patient lacks an HLA matched sibling donor.
• Meets criteria nonhematopoietic organ function according to NCH BMT SOP09.
• If subjects have received a first HCT, they must be eligible for a second HCT if their disease has recurred.
• High resolution HLA and KIR typing
• The subject cannot have an active untreated infection. Viremia by PCR analysis is not considered an active infection but may require immediate viral prophylaxis. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti- fungal therapy and be asymptomatic.
• Negative pregnancy test for females ≥11 years of age or post- menarche.
• Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator. (Non-childbearing potential defined as pre-menarche, greater than one year post-menopausal or surgically sterilized).
• Subjects must be ≤30 years at the time of consent.
• Signed consent by parent/guardian and assent if appropriate for subjects < 18 years of age. Signed consent by patient/subject if ≥18 years of age.

Exclusion Criteria

• Patient does not have a suitable donor who is willing and able (meets donor criteria).
• Patient has donor-specific anti-HLA antibodies at the time of enrollment
• Patient reports a history of allergic reactions to murine protein

Donor Eligibility:

• The donor must be ≥18 years of age at the time of the informed consent conference.
• The donor must be a related donor
• The donor will be evaluated according to the current NCH BMT SOP 04 and must meet all criteria.
• The donor must be able and willing to undergo G-CSF mobilization and stem cell apheresis.
• The patient does not have donor specific anti-HLA antibodies

• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Nationwide Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nationwide Children's Hospital

Columbus, Ohio, United States

Countries

United States

Other Identifiers

IRB17-00516

Identifier Type: -

Identifier Source: org_study_id