T-cell Receptor α/β Depleted Donor Lymphocyte Infusion

Study Overview
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Brief Summary
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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.

Official Title
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Phase I Dose Escalation of T-cell Receptor α/β Depleted Donor Lymphocyte Infusions Following CD34+- Selected Allogeneic Stem Cell Transplantation From Related & Unrelated Donors in Patients With Lymphoid, Myeloid or Plasma Cell Malignancies

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

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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HLA Matched Cohort I<br>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<br>* T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients<br>|
| Experimental: HLA Matched Cohort II<br>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<br>* T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients<br>|
| Experimental: HLA Matched Cohort III<br>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<br>* T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients<br>|
| Experimental: HLA Mismatched Cohort I<br>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<br>* T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients<br>|
| Experimental: HLA Mismatched Cohort II<br>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<br>* T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients<br>|
| Experimental: HLA Mismatched Cohort III<br>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<br>* T-cell Receptor α/β Depleted Donor Lymphocyte Infusions following CD34+-selected Allogeneic Stem Cell Transplantation from Related and Unrelated Donors for Patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants in remission | Remission - measured by absence of signs and symptoms | 2 years | 
| Number of participants with transplant-associated viral complications | Transplant-associated viral complications - measured by viral infections associated with transplant | 2 years | 
| Disease free survival- measured by absence of relapse/recurrence or death. | 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. | 2 years | 
| Overall survival - measured by death | Overall survival - measured by death | 2 years |