αβT Cell/CD19+ B Cell Depletion for Alternative Donor Allogeneic Hematopoietic Cell Transplantation (HSCT) (TB19DHCT)

αβT Cell/CD19+ B Cell Depletion for Alternative Donor Allogeneic Hematopoietic Cell Transplantation (HSCT) for Children and Young Adults With Hematologic Malignancies

This is a study utilizing the Magnetic-activated cell sorting (CliniMACS®) Alpha-Beta T-cell (αβT)/Cluster of Differentiation 19 (CD19), also called B lymphocyte antigen CD19 depletion device for Children and Young Adults with Hematologic Malignancies undergoing alternative Donor Allogeneic Hematopoietic Cell Transplantation (HSCT). Patients will receive an allogenic HSCT from a matched unrelated donor (MUD), mismatch unrelated donor (MMUD) or a mismatched related (haploidentical) donor. Patients will receive a granulocyte-colony stimulating factor (G-CSF) ± Plerixafor donor mobilized peripheral stem cell donor transplant following CliniMACS® αβT cell/CD19+B cell depletion. Cluster of Differentiation 34 (CD34) and αβT cell content of the graft is determined based on the transplant indication.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Malignancy; Hematopoietic Stem Cell Transplantation
• Intervention / Treatment: Device: CliniMACS®

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Clelie Peck; Phone Number: 614-722-5634; Email: clelie.peck@nationwidechildrens.org
• Study Contact Backup: Name: Lauren Rayman; Phone Number: 614-722-3729; Email: lauren.rayman@nationwidechildrens.org

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Principal Investigator: Rolla Abu-Arja, MD
      • Contact: Rolla Abu-Arja, MD; Phone Number: 614-722-3250; Email: rolla.abu-arja@nationwidechildrens.org
      • Contact: Hemalatha Rangarajan, MD; Email: hemalatha.rangarajan@nationwidechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≤ 30 years
• Patients who will benefit from an allogenic stem cell transplant to treat underlying primary hematological malignancy and lacks a suitably available matched sibling donor.
• Karnofsky Index or Lansky Performance Scale ≥ 60 % on pre-transplant evaluation.
• Karnofsky scores must be used for patients > 16 years of age and Lansky scores for patients ≤ 16 years of age.
• Patient or legal guardian must give informed consent if patient is ≥ 18 years. Legal guardian must give informed consent (and patient must give assent if appropriate) if patient is < 18 years.
• Adequate organ function (within 4 weeks of initiation of preparative regimen). For patients receiving Myeloablative conditioning (MAC) on this platform, they should meet organ function to tolerate MAC. Similar if patients are receiving Reduced intensity conditioning (RIC).
• High resolution human leukocyte antigen (HLA) available

Exclusion Criteria:

• Patient does not have a suitable donor who is willing and able (meets donor criteria).
• Patient reports a history of allergic reactions to murine protein
• Pregnant or lactating females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants. Female patients of childbearing potential females ≥11 years of age or post- menarche and should have a negative pregnancy test
• Patients with HIV or uncontrolled fungal, bacterial or viral infections are excluded. Patients with history of fungal disease during induction therapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by CT evaluation. Viremia by Pluripotency Check (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 -
• Patients receiving umbilical cord blood and matched sibling donor transplants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSCT using TCR αβ/CD19+ depleted grafts; Allogeneic HSCT using the TCR αβ/CD19+ depleted platform and grafts from alternative donors (MUD, MMUD and haploidentical)	Device: CliniMACS®; CliniMACS® αβT cell/CD19+B cell depletion device for Children and Young Adults with Hematologic Malignancies undergoing alternative Donor Allogeneic Hematopoietic Cell Transplantation (HSCT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year overall survival of patients undergoing allogeneic HSCT using the T-Cell Receptor (TCR) αβ/CD19+ depleted platform and grafts from alternative donors (MUD, MMUD and haploidentical)	One-year overall survival of patients undergoing allogeneic HSCT	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil and platelet engraftment following TCR αβ/CD19+ depleted alternative donor (MUD, MMUD and haploidentical) HSCT	Neutrophil and platelet engraftment by day 100	100 days
Incidence of final status graft failure	Incidence of final status graft failure by 1 year	1 year
Incidence grade III-IV acute graft versus host disease (GVHD)	Incidence grade III-IV acute graft versus host disease (GVHD) by 1 year	1 year
Incidence of chronic GVHD	Incidence of chronic GVHD by 1 year	1 year
100 day and 1 year Transplant related mortality	100 day and 1 year Transplant related mortality by 1 year	1 year
1 year Event free survival	1 year Event free survival	1 year

Collaborators and Investigators

• Sponsor: Nationwide Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: October 3, 2023
• First Submitted That Met QC Criteria: October 10, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: TB19DHCT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes