Preemptive Infusion of Donor Lymphocytes Depleted of TCR + T Cells + CD19+ B Cells Following ASCT

NCT03939585 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: CASE1Z19
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to reduce the risk of cancer relapse by giving a donor lymphocyte infusion (DLI) to boost the immune system early after a stem cell transplant so that leukemia cells that escaped chemotherapy can be detected and killed. This DLI will contain mostly lymphocytes that have graft versus tumor effect with low risk of graft versus host disease. Because the process of giving a DLI in the first four weeks after a transplant has not been approved by the Food and Drug Administration (FDA), this study in investigational (experimental).

Conditions

Allogeneic Stem Cell Transplant Candidate; Acute Myeloid/Lymphoblastic Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Lymphoproliferative Disorders

Outcome Measures

Primary Outcomes (1)

• Incidence of Grade III-IV GVHD, Grade II GVHD requiring systemic treatment or new onset, severe neutropenia requiring growth factor support at Day 100 and T+6 months.

  This study seeks to measure if donor lymphocytes depleted of TCR-αβ T cells and B cells can be infused on Day 28 following allogeneic stem cell transplantation without inducing Grade III-IV graft versus host disease, Grade II GVHD requiring systemic treatment or new onset, severe neutropenia requiring growth factor support. The endpoint associated with this objective is 'incidence of Grade III-IV graft versus host disease, Grade II GVHD requiring systemic treatment or new onset, severe neutropenia requiring growth factor support at Day 100 and T+6 months.'

  up to 30 days after lymphocyte product infusion

Secondary Outcomes (7)

• Different lymphocyte types in the infused product reported as cells per kilogram body weight of the recipient

  28 days post-transplant

• Number of disease relapse events in the first 6 moths following stem cell transplant

  6 months from start of treatment

• Number of disease relapse events in the first 1 year following stem cell transplant

  1 year from start of treatment

• Average time to disease relapse from date of transplant

  6 months from start of treatment

• Average time to disease relapse from date of transplant

  1 year from start of treatment

Study Arms (1)

NK/γδ T cell-enriched cell therapy product

EXPERIMENTAL

This study will treat 10 participants with the donor NK/TCR-γδ T cell product. Of those 10 participants, 5 would have 10/10 HLA matched sibling donors (MSD) while 5 would have partially matched, related (haplo) donors. * 27 days post transplant, the participant's donor will undergo a second, non-mobilized leukapheresis to obtain peripheral blood mononuclear cells (PBMCs). * Donor PBMCs will be processed next day (Day T+28) to obtain the NK cell/TCRγδ T cell product for same day infusion if the participant remains aGVHD free and clinically stable. * Participants will continue routine post-transplant and GVHD monitoring, as well as disease assessment at 56 days, 100 days, 6 months and 1 year following transplant. * Blood samples will be obtained on T=0, T+7, 14, 21 and 28 days and then weekly until T + 56 days, then on T+100 days, + 6 months and + 12 months. If immune-mediated adverse events occur (GVHD, CRS etc) additional blood samples will be obtained at onset and resolution.

Biological: Cellular therapy product

Interventions

Cellular therapy product BIOLOGICAL

Cellular therapy product: Allogeneic transplant donor lymphocytes, depleted of TCR-αβ T cells and B cells; enriched for NK cells and TCRγδ T cells. * Infused using venous catheter on post-transplant Day 28 (+ 7 days). * Single infusion of entire lymphocyte product derived from two-blood volume leukapheresis (non-mobilized).

NK/γδ T cell-enriched cell therapy product

Eligibility Criteria

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

You may qualify if:

• Subjects must have histologic or cytologic confirmation of ANY hematologic malignancy
• Allogeneic stem cell transplant is indicated as management of underlying hematologic malignancy.
• Participant has organ function (cardiac, lung and liver) considered adequate to undergo conditioning chemotherapy and allogeneic stem cell transplant in the assessment of the clinical program
• Participant has a 10/10 HLA-matched sibling donor OR has a HLA-haploidentical donor available (in the absence of a 10/10 HLA matched unrelated donor)
• The related transplant donor is willing, available and consents to undergo a second, non-mobilized leukapheresis for the procurement of donor lymphocytes
• The related transplant donor is 18 years of age or older
• Subjects must have the ability to understand and the willingness to sign a written informed consent document or provide assent.

You may not qualify if:

• Subject is unwilling to receive a prophylactic donor lymphocyte infusion per study protocol.
• The related donor is unwilling or unavailable to undergo a second, non- mobilized leukapheresis for the procurement of donor lymphocytes.
• Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 4 weeks prior to study entry and for the duration of study participation. Women of child-bearing age must have documented negative pregnancy test prior to start of conditioning regimen for stem cell transplantation and a repeat negative pregnancy test prior to infusion of the lymphocyte product.
• Patients with any of the following organ function abnormalities: Left ventricular ejection fraction (LVEF) \< 45%; DLCO \<45% of expected value corrected for alveolar volume and hemoglobin; Serum Creatinine \>2 times the upper limit of normal.

Sponsors & Collaborators

• Leland Metheny: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Lymphoproliferative Disorders

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Study Officials

• Leland Metheny, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a Phase I, pilot study designed to treat 10 participants with the donor NK/γδ T cell-enriched product on transplant Day 28.

Study Record Dates

• First Submitted: May 3, 2019
• First Posted: May 7, 2019
• Study Start: December 1, 2024
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Investigators who provide a methodologically sound proposal for use of requested data

Locations

US (1)