Allogeneic Stem Cell Transplant CandidatePhase 1NCT03939585

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

A Phase 1 study testing Cellular therapy product in people with Allogeneic Stem Cell Transplant Candidate and Acute Myeloid/Lymphoblastic Leukemia, run by Leland Metheny at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Allogeneic Stem Cell Transplant Candidate, Acute Myeloid/Lymphoblastic Leukemia, Myelodysplastic Syndrome
What is being tested?: Cellular therapy product
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: 1 Dec 2024to 1 Jun 2026
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106

Other trials in United States

About this study

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

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).

Read the 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.

Conditions: Allogeneic Stem Cell Transplant Candidate, Acute Myeloid/Lymphoblastic Leukemia, Myelodysplastic Syndrome, Myeloproliferative Neoplasm, Lymphoproliferative Disorders
Being tested: Cellular therapy product
Medical subject headings: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Myeloproliferative Disorders, Lymphoproliferative Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Cellular therapy productBiological
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).

Study groups in NCT03939585
Study group	Role	What they receive
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. Receives: Biological: Cellular therapy product

What is being measured

The primary outcome is the main question the study is designed to answer.

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.'
Measured: 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
Number of different lymphocyte types in the infused product measured as cells per kilogram body weight of the recipient
Measured: 28 days post-transplant
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.
Measured: 6 months from start of treatment
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.
Measured: 1 year from start of treatment
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.
Measured: 6 months from start of treatment
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.
Measured: 1 year from start of treatment
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
Measured: 6 months from start of treatment
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.
Measured: 6 months from start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Dec 20241 Jun 2026

First posted7 May 2019
Study start1 Dec 2024 (estimated)
Primary completion1 Jun 2025 (estimated)
Study completion1 Jun 2026 (estimated)

Why it stopped: Lack of funding

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Allogeneic Stem Cell Transplant CandidateStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
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)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03939585
Sponsor's protocol ID: CASE1Z19
Status last verified: Dec 2024
First submitted: 3 May 2019
Last updated: 5 Dec 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Individual participant data that underlie or influence the results observed from the study

Study at a glance

From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Preemptive Infusion of Donor Lymphocytes Depleted of TCR (Alpha-beta) + T Cells and CD19+ B Cells Following Allogeneic Stem Cell Transplantation
ClinicalTrials.gov ID: NCT03939585
Acronym / sponsor ID: CASE1Z19
Conditions: Allogeneic Stem Cell Transplant Candidate, Acute Myeloid/Lymphoblastic Leukemia, Myelodysplastic Syndrome, Myeloproliferative Neoplasm, Lymphoproliferative Disorders
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Lack of funding
Enrolment: 0 participants (actual)
Lead sponsor: Leland MethenyUniversity, hospital or other
Study start: 1 Dec 2024 (estimated)
Primary completion: 1 Jun 2025 (estimated)
Study completion: 1 Jun 2026 (estimated)
First posted: 7 May 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
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.

Arm	Type	Receives
NK/γδ T cell-enriched cell therapy product	Experimental	Biological: Cellular therapy productThis 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Cellular therapy productCellular 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).	Biological	NK/γδ T cell-enriched cell therapy product

Primary outcome

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.
Time frame: up to 30 days after lymphocyte product infusion
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.'

7 secondary outcomes

Different lymphocyte types in the infused product reported as cells per kilogram body weight of the recipient
Time frame: 28 days post-transplant
Number of disease relapse events in the first 6 moths following stem cell transplant
Time frame: 6 months from start of treatment
Number of disease relapse events in the first 1 year following stem cell transplant
Time frame: 1 year from start of treatment
Average time to disease relapse from date of transplant
Time frame: 6 months from start of treatment
Average time to disease relapse from date of transplant
Time frame: 1 year from start of treatment
Occurrence of reactivated Epstein Barr Virus (EBV) and/or Cytomegalovirus viremia (CMV) as measured by number of study subjects developing measurable viremia
Time frame: 6 months from start of treatment
Average time to first occurrence of reactivated EBV and/or CMV
Time frame: 6 months from start of treatment

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
Individual participant dataSharing planned: Yes. Individual participant data that underlie or influence the results observed from the study

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Leland Metheny, MD principal investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cellular therapy product in people with Allogeneic Stem Cell Transplant Candidate and Acute Myeloid/Lymphoblastic Leukemia, run by Leland Metheny at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: up to 30 days after lymphocyte product infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03939585.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.