Clinical trial NCT03939585: 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
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Allogeneic Stem Cell Transplant Candidate
Acute Myeloid/Lymphoblastic Leukemia
Myelodysplastic Syndrome
Myeloproliferative Neoplasm
Lymphoproliferative Disorders
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2019-05-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
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.
timeFrame: up to 30 days after lymphocyte product infusion
Secondary outcomes:
measure: Different lymphocyte types in the infused product reported as cells per kilogram body weight of the recipient
timeFrame: 28 days post-transplant
measure: Number of disease relapse events in the first 6 moths following stem cell transplant
timeFrame: 6 months from start of treatment
measure: Number of disease relapse events in the first 1 year following stem cell transplant
timeFrame: 1 year from start of treatment
measure: Average time to disease relapse from date of transplant
timeFrame: 6 months from start of treatment
measure: Average time to disease relapse from date of transplant
timeFrame: 1 year from start of treatment
measure: Occurrence of reactivated Epstein Barr Virus (EBV) and/or Cytomegalovirus viremia (CMV) as measured by number of study subjects developing measurable viremia
timeFrame: 6 months from start of treatment
measure: Average time to first occurrence of reactivated EBV and/or CMV
timeFrame: 6 months from start of treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
name: Leland Metheny, MD
role: PRINCIPAL_INVESTIGATOR
References: