Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Young Adults

Allogeneic Hematopoietic Stem Cell Transplantation From an HLA-partially Matched Related or Unrelated Donor After TCR αβ+T Cells/CD19+ B Cell Depletion in Children and Young Adults Affected by Malignant or Non-Malignant Hematological Disorders

The purpose of the CliniMACS® TCRαβ-Biotin System and CliniMACS® CD19 is to improve the safety and efficacy of allogeneic HLA-partially matched related or unrelated donors HSCT when no matched donors are available, to treat malignant and nonmalignant disorders for which HSCT is the recommended best available therapy. Initially this device will be used in a single-center, open-label, single-arm, phase II clinical trial to evaluate the efficacy of haploidentical PBSC grafts depleted of TCRα/β+ and CD19+ cells using the CliniMACS® TCRαβ/CD19 System in children and adults with hematological and non-hematological malignancies.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Diseases
• Intervention / Treatment: Biological: Allogeneic Stem Cell Transplant; Device: CliniMACS TCR α/β Reagent Kit and CliniMACS CD19

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94306
      • Recruiting
      • Lucile Packard Children's Hospital
      • Contact: SCGT Clinical Trials Program; Phone Number: 650-497-2447; Email: DL-SCTIntakeCoordinators@stanfordchildrens.org
      • Sub-Investigator: David Shyr, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age < 60 years and > 1 month;
2. Life expectancy > 10 weeks;
3. Patients deemed eligible for allogeneic HSCT per institutional guidelines;
4. Patients with life-threatening hematological malignancies and non-malignant disorders that could benfit from HSCT;
5. A minimum genotypic identical match of 5/10 is required;
6. The donor and recipient must be identical, as determined by high resolution typing, in at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, and HLA-DRB1;
7. Lansky/Karnofsky score > 50;
8. Signed written informed consent;
9. Male and female subjects of childbearing potential must agree to use an effective means of birth control to avoid pregnancy throughout the transplant procedure, while on immunosuppression, and if the subject experiences any chronic GvHD.

Exclusion Criteria:

1. Pregnant or lactating females;
2. Greater than Grade II acute GvHD or severe, unmanaged chronic extensive GvHD due to a previous allograft at the time of inclusion;
3. Dysfunction of liver (ALT/AST > 10 times upper normal value, or direct bilirubin > 3 times upper normal value), or unmanageable dysfunction of renal function;
4. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction < 30%);
5. Current active infectious disease (including positive HIV serology or viral RNA);
6. Serious concurrent uncontrolled medical disorders;
7. Lack of patient's/parents'/guardian's informed consent;
8. Any severe concurrent disease which, in the judgement of the sponsor-investigator, would place the patient at increased risk during participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stem Cell Transplant -Malignant; The participant with a malignancy will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. Participants will be followed for outcomes for two years.	Biological: Allogeneic Stem Cell Transplant; The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.; Device: CliniMACS TCR α/β Reagent Kit and CliniMACS CD19; The CliniMACS™system can be used to selectively enrich or reduce specific cell populations based on the magnetic cell selection (MACS) technology developed by Miltenyi Biotec. Cell mixtures can be separated in a magnetic field using one or more immunomagnetic- labeled antibodies specific for the cell types of interest (e.g.TCR αβ+ T cells and CD19+ B cells from HPC(A) products).
Experimental: Stem Cell Transplant - Non-Malignant; The participant with a non-malignant disease will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. Participants will be followed for outcomes for two years.	Biological: Allogeneic Stem Cell Transplant; The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.; Device: CliniMACS TCR α/β Reagent Kit and CliniMACS CD19; The CliniMACS™system can be used to selectively enrich or reduce specific cell populations based on the magnetic cell selection (MACS) technology developed by Miltenyi Biotec. Cell mixtures can be separated in a magnetic field using one or more immunomagnetic- labeled antibodies specific for the cell types of interest (e.g.TCR αβ+ T cells and CD19+ B cells from HPC(A) products).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with grade II-IV acute GvHD at day 100 after HSCT	Through Day 100 after HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with successful engraftment at day 42 after HSCT		Day 42 after HSCT
Number of participants with grade III-IV acute GvHD at day 100 after HSCT		Through Day 100 after HSCT
Number of participants with chronic GVHD at 1 year after HSCT		1 year after HSCT
Leukemia-free survival at 1 year after HSCT	Leukemia-free survival defined as the time of enrollment to disease relapse or death from any cause.	1 year after HSCT
Leukemia-free survival at 2 years after HSCT	Leukemia-free survival defined as the time of enrollment to disease relapse or death from any cause.	2 years after HSCT
Number of participants with secondary graft failure at 1 year after HSCT		1 year after HSCT
Number of participants with secondary graft failure at 2 years after HSCT		2 years after HSCT

Collaborators and Investigators

• Sponsor: Alice Bertaina
• Investigators: Principal Investigator: Alice Bertaina, MD, PhD, Associate Professor of Pediatrics, Stem Cell Transplantation

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases
• Other Study ID Numbers: IRB-53822; BMT 361 - Alpha Beta IDE (Other Identifier: Stanford School of Medicine)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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