T-cell Receptor α/β Depleted Donor Lymphocyte Infusion

Guenther Koehne

Status and phase: Terminated; Phase 1

Conditions: Myeloid Malignancy; Plasma Cell Tumor; Lymphoid Leukemia, Acute

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05350163

2019-KOE-004

Details and patient eligibility

About

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.

Enrollment: 11 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

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

• Patients with active acute GvHD.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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11 participants in 6 patient groups

HLA Matched Cohort I

Experimental group

Description:

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)

Treatment:

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

HLA Matched Cohort II

Experimental group

Description:

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

Treatment:

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

HLA Matched Cohort III

Experimental group

Description:

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

Treatment:

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

HLA Mismatched Cohort I

Experimental group

Description:

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)

Treatment:

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

HLA Mismatched Cohort II

Experimental group

Description:

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

Treatment:

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

HLA Mismatched Cohort III

Experimental group

Description:

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

Treatment:

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