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

Primary Purpose

Allogeneic Stem Cell Transplant Candidate, Acute Myeloid/Lymphoblastic Leukemia, Myelodysplastic Syndrome

Status

Not yet recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cellular therapy product

About this trial

This is an interventional treatment trial for Allogeneic Stem Cell Transplant Candidate

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NK/γδ T cell-enriched cell therapy product

Arm Description

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.

Outcomes

Primary Outcome Measures

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.'

Secondary Outcome Measures

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

Number of different lymphocyte types in the infused product measured as cells per kilogram body weight of the recipient

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

To describe occurrence of disease relapse, the number of disease relapse events in the first year following stem cell transplant will be reported.

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

To describe occurrence of disease relapse, the number of disease relapse events in the first year following stem cell transplant will be reported.

Average time to disease relapse from date of transplant

To describe occurrence of disease relapse, the average time to disease relapse from date of transplant in the first six months following stem cell transplant will be reported.

Average time to disease relapse from date of transplant

To describe occurrence of disease relapse, the average time to disease relapse from date of transplant in the first year following stem cell transplant will be reported.

Occurrence of reactivated Epstein Barr Virus (EBV) and/or Cytomegalovirus viremia (CMV) as measured by number of study subjects developing measurable viremia

To describe the occurrence of post-transplant re- activation and/or infections with viruses such as CMV, and/or EBV, the number of study subjects developing measurable viremia will be reported

Average time to first occurrence of reactivated EBV and/or CMV

To describe the occurence of post-transplant re- activation and/or infections with viruses such as CMV, and/or EBV, median time to first occurrence of reactivated EBV and/or CMV will be reported.

Full Information

NCT ID

NCT03939585

First Posted

May 3, 2019

Last Updated

May 24, 2023

Sponsor

Leland Metheny

1. Study Identification

Unique Protocol Identification Number

NCT03939585

Brief Title

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

Official Title

Preemptive Infusion of Donor Lymphocytes Depleted of TCR (Alpha-beta) + T Cells and CD19+ B Cells Following Allogeneic Stem Cell Transplantation

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

June 2023 (Anticipated)

Primary Completion Date

November 2023 (Anticipated)

Study Completion Date

September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Leland Metheny

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

Detailed Description

The primary objective of this study is to investigate 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 and or new onset, severe neutropenia requiring growth factor support. This study also seeks to characterize the lymphocyte subsets obtained following depletion of TCR-αβ T cells and B cells from non-mobilized, leukapheresis products. Additionally, this study will attempt to describe occurrence of disease relapse and to describe the occurrence of post-transplant re- activation and/or infections with viruses such as CMV, and EBV.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

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.

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

NK/γδ T cell-enriched cell therapy product

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Cellular therapy product

Intervention Description

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).

Primary Outcome Measure Information:

Title

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.

Description

Time Frame

up to 30 days after lymphocyte product infusion

Secondary Outcome Measure Information:

Title

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

Description

Number of different lymphocyte types in the infused product measured as cells per kilogram body weight of the recipient

Time Frame

28 days post-transplant

Title

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

Description

To describe occurrence of disease relapse, the number of disease relapse events in the first year following stem cell transplant will be reported.

Time Frame

6 months from start of treatment

Title

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

Description

To describe occurrence of disease relapse, the number of disease relapse events in the first year following stem cell transplant will be reported.

Time Frame

1 year from start of treatment

Title

Average time to disease relapse from date of transplant

Description

To describe occurrence of disease relapse, the average time to disease relapse from date of transplant in the first six months following stem cell transplant will be reported.

Time Frame

6 months from start of treatment

Title

Average time to disease relapse from date of transplant

Description

To describe occurrence of disease relapse, the average time to disease relapse from date of transplant in the first year following stem cell transplant will be reported.

Time Frame

1 year from start of treatment

Title

Occurrence of reactivated Epstein Barr Virus (EBV) and/or Cytomegalovirus viremia (CMV) as measured by number of study subjects developing measurable viremia

Description

To describe the occurrence of post-transplant re- activation and/or infections with viruses such as CMV, and/or EBV, the number of study subjects developing measurable viremia will be reported

Time Frame

6 months from start of treatment

Title

Average time to first occurrence of reactivated EBV and/or CMV

Description

To describe the occurence of post-transplant re- activation and/or infections with viruses such as CMV, and/or EBV, median time to first occurrence of reactivated EBV and/or CMV will be reported.

Time Frame

6 months from start of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Leland Metheny, MD

Phone

1-800-641-2422

CTUReferral@UHhospitals.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Leland Metheny, MD

Organizational Affiliation

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Leland Metheny, MD

Phone

800-641-2422

CTUReferral@UHhospitals.org

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant data that underlie or influence the results observed from the study

IPD Sharing Time Frame

Beginning 3 months and ending 5 years following article publication

IPD Sharing Access Criteria

Investigators who provide a methodologically sound proposal for use of requested data

Learn more about this trial

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

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