T-cell Receptor α/β Depleted Donor Lymphocyte Infusion

NCT05350163 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 2019-KOE-004
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study is being conducted to treat patients who have a certain type of malignancy (lymphoid or myeloid) with immune effector cells after a T-cell depleted allogeneic hematopoietic cell transplantation (TCD HSCT). This study is designed to see whether an investigational cellular product of immune cells obtained from a donor's cells that have been treated so that the type of cells that can lead to graft vs host disease have been removed can be safely administered. These cell products are administered following the initial stem cell transplant to assess the effect and improvement on minimal residual disease status, infectious complication, progression-free and overall survival.

Conditions

Lymphoid Leukemia, Acute; Myeloid Malignancy; Plasma Cell Tumor

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs)

  TE-SAEs are defined as the composite of death, non-fatal pulmonary embolism, stroke, acute graft versus host disease (GvHD), and clinically significant laboratory test abnormalities.

  30 days post-infusion

Secondary Outcomes (4)

• Number of Participants in Remission

  2 years

• Number of Participants With Transplant-associated Viral Complications

  2 years

• Disease Free Survival- Measured by Absence of Relapse/Recurrence or Death.

  2 years

• Overall Survival

  2 years

Study Arms (6)

HLA Matched Cohort I

EXPERIMENTAL

5 x 10\^5/kg at 6-7 weeks post-transplant (Group A), 4-5 weeks post-transplant (Group B), or 2-3 weeks post-transplant (Group C)

Biological: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions

HLA Matched Cohort II

EXPERIMENTAL

5 x 10\^5/kg starting time point X (whichever was safest as determined by Matched Cohort I), 1 x 10\^6/kg 3-4 weeks after first dose, and 1 x 10\^6/kg 3-4 weeks after second dose

Biological: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions

HLA Matched Cohort III

EXPERIMENTAL

5 x 10\^5/kg starting time point X (whichever was safest as determined by Matched Cohort I), 1 x 10\^6/kg 3-4 weeks after first dose, and 2 x 10\^6/kg 3-4 weeks after second dose

Biological: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions

HLA Mismatched Cohort I

EXPERIMENTAL

1 x 10\^5/kg at 6-7 weeks post-transplant (Group A), 4-5 weeks post-transplant (Group B), or 2-3 weeks post-transplant (Group C)

Biological: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions

HLA Mismatched Cohort II

EXPERIMENTAL

1 x 10\^5/kg starting time point Y (whichever was safest as determined by Mismatched Cohort I), 5 x 10\^5/kg 3-4 weeks after first dose, and 5 x 10\^5/kg 3-4 weeks after second dose

Biological: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions

HLA Mismatched Cohort III

EXPERIMENTAL

1 x 10\^5/kg starting time point Y (whichever was safest as determined by Mismatched Cohort I), 5 x 10\^5/kg 3-4 weeks after first dose, and 1 x 10\^6/kg 3-4 weeks after second dose

Biological: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions

Interventions

T-cell Receptor α/β Depleted Donor Lymphocyte Infusions BIOLOGICAL

T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients

HLA Matched Cohort I; HLA Matched Cohort II; HLA Matched Cohort III; HLA Mismatched Cohort I; HLA Mismatched Cohort II; HLA Mismatched Cohort III

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with hematologic malignancies that are candidates CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation.
• Patients must have a Karnofsky (adult) Performance Status of at least 70%.
• Patients must have adequate organ function measured by:
• Cardiac: asymptomatic or if symptomatic then left ventricular ejection fraction (LVEF) at rest must be 50% and must improve with exercise.
• Hepatic: \< 3x upper limit of normal (ULN) AST and \< 1.5 mg/dL total serum bilirubin, unless there is congenital benign hyperbilirubinemia. Patients with higher bilirubin levels due to causes other than active liver disease is also eligible with Pl approval (e.g., patients with PNH, Gilbert's disease or other hemolytic disorders).
• Renal: serum creatinine: ≤ 1.2 mg/dL or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) \> 40 mL/min (measured or calculated/estimated).
• Pulmonary: asymptomatic or if symptomatic, diffusing capacity of the lungs for carbon monoxide (DLCO) 50% of predicted (corrected for hemoglobin).
• Each patient must be willing to participate as a research subject and must sign an informed consent form.

You may not qualify if:

• Patients with active acute GvHD.

Sponsors & Collaborators

• Guenther Koehne: lead

Study Sites (1)

Miami Cancer Institute at Baptist Health, Inc

Miami, Florida, 33176, United States

Location

Related Publications (32)

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Related Links

• Miami Cancer Institute Website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Plasmacytoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell

Limitations and Caveats

Several of the participants had been on study for more than a year by the time the study was terminated. However, because the study was terminated early, the study did not accrue to the target, some cohorts had zero participants accrued, and no participants completed the study. Therefore, no conclusions can be drawn at this time.

Results Point of Contact

• Title: Director, Research Concept & Protocol Development
• Organization: Miami Cancer Institute at Baptist Health, Inc.

MCIResearchConceptAndProtocolDev@baptisthealth.net

(786) 527-9546

Study Officials

• Guenther Koehne, MD, PhD

  Miami Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director and Chief of Blood and Marrow Transplant, Hematologic Oncology and Benign Hematology

Model Details: The model is both parallel and sequential, in that Matched and Mismatched strata run in parallel and independently. Within each stratum, Cohorts I-III are filled sequentially. In addition, Cohort I of each stratum has three groups (A-C) that are filled sequentially.

Study Record Dates

• First Submitted: April 22, 2022
• First Posted: April 28, 2022
• Study Start: April 5, 2022
• Primary Completion: September 18, 2023
• Study Completion: September 18, 2023
• Last Updated: December 10, 2024
• Results First Posted: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)