T-cell Receptor α/β Depleted Donor Lymphocyte Infusion

Phase 1

Terminated

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

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.

Recruitment & Eligibility

Inclusion Criteria

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.

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
HLA Matched Cohort I	T-cell Receptor α/β Depleted Donor Lymphocyte Infusions	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)
HLA Matched Cohort II	T-cell Receptor α/β Depleted Donor Lymphocyte Infusions	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
HLA Matched Cohort III	T-cell Receptor α/β Depleted Donor Lymphocyte Infusions	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
HLA Mismatched Cohort I	T-cell Receptor α/β Depleted Donor Lymphocyte Infusions	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)
HLA Mismatched Cohort II	T-cell Receptor α/β Depleted Donor Lymphocyte Infusions	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
HLA Mismatched Cohort III	T-cell Receptor α/β Depleted Donor Lymphocyte Infusions	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

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs)	30 days post-infusion	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants in Remission	2 years	Remission - measured by absence of signs and symptoms
Number of Participants With Transplant-associated Viral Complications	2 years	Transplant-associated viral complications - measured by viral infections associated with transplant
Disease Free Survival- Measured by Absence of Relapse/Recurrence or Death.	2 years	Disease free survival - measured by (absence of ) relapse/recurrence or death. Relapse and recurrence, both will be measured by greater than 5% circulating leukemic blasts in the marrow or peripheral blood and/or the presence of blasts in any extra medullary site and/or disease determined by clinical assessment.
Overall Survival	2 years	Overall survival - measured by death

Locations (1): Miami Cancer Institute at Baptist Health, Inc
🇺🇸
Miami, Florida, United States
Miami Cancer Institute at Baptist Health, Inc
🇺🇸Miami, Florida, United States