Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

NCT03717480 | Terminated Phase 2 Results DMC FDA Device

• 1 other identifier: 18-270
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying the removal of a subset of white blood cells (called alpha/beta T cells) from the donor product using a cell separation device before the product is transplanted into the participant. The device used to remove the α/βT cells in this study is:

• CliniMACS® TCR α/β Reagent System

Conditions

Hematologic Malignancy

Keywords

Graft vs. Host Disease; Hematologic Malignancy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Severe Acute GVHD-free Survival

  Number of participants with severe acute GVHD-free survival will be assessed at 100 days post-SCT

  100 Days

Secondary Outcomes (11)

• Number of Participants With Grades II-IV Acute GVHD

  2 years

• Number of Participants With Chronic GVHD

  2 years

• Number of Participants With GVHD and Relapse Free Survival (GRFS)

  2 years

• Number of Participants With Immunosuppression-free Survival

  2 years

• Number of Participants With Hematologic Recovery

  2 years

Study Arms (1)

TCR α/β Reagent System

EXPERIMENTAL

* The stem cell apheresis product will be depleted of TCRαβ T cells by negative selection using the automated CliniMACS® Plus device. * CD34+ stem cell counts will be obtained before and after processing with the Miltenyi ClinicMACs device

Device: ClinicMACs

Interventions

ClinicMACs DEVICE

The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to participants

TCR α/β Reagent System

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnoses and stage at time of transplant admission:
• Acute leukemia (AML or ALL or MPAL) in first or subsequent remission
• Myelodysplastic syndromes (MDS) with \<10% marrow blasts
• Myeloproliferative neoplasm (MPN) with \<10% marrow blasts
• CMML with less than 10% marrow blast
• CML accelerated phase or second or subsequent chronic phase
• Non-Hodgkin's lymphoma in PR or CR2 or beyond
• Hodgkin lymphoma in PR or CR2 or beyond
• Age 18-65 years
• Patient has a related or unrelated donor who is 8 or 9 out of 10 match at HLA A, B, C, DRB1 and DQB1, based on allele level typing.
• Patient ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)
• Patient deemed to be appropriate candidate for myeloablative conditioning transplantation.
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patient with active HIV infection
• Chronic active hepatitis B infection (HepB surface Ag+ or detectable Hep B viral load)
• Prior allogeneic hematopoietic stem cell transplantation
• Impaired cardiac function- ejection fraction \< 40%
• Impaired pulmonary function- pretransplant FEV1, DLCO \< 50%
• Impaired renal function, based on
• Serum creatinine \> 2.0 mg/dl
• Impaired liver function unrelated to primary disease, based on
• ALT or AST \> 3x ULN, or Total Bilirubin \> 2.0mg/dl (with exception for known or suspected Gilbert's disease)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Women who are pregnant or breast feeding. Women of child bearing potential must have a negative serum pregnancy test at study entry.
• Participants who are receiving any other investigational agents are eligible but such agent must be discontinued before admission for HSCT, and if resumption of investigation agent is planned after HSCT, this must be approved by the study PI.
• Participants with known active CNS disease. CNS disease that has been treated is eligible

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Graft vs Host Disease

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Limitations and Caveats

Early termination after accrual of only one evaluable subject resulted in an insufficient sample size for analysis.

Results Point of Contact

• Title: Dr. Vincent Ho
• Organization: Dana-Farber Cancer Institute

vincent_ho@dfci.harvard.edu

617-632-6256

Study Officials

• Vincent T Ho, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: October 24, 2018
• Study Start: January 21, 2020
• Primary Completion: April 26, 2021
• Study Completion: April 26, 2021
• Last Updated: May 10, 2022
• Results First Posted: May 10, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)