Safety and Efficiency of γδ T Cell Against Hematological Malignancies After Allo-HSCT

Study Overview
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Brief Summary
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This study investigates the infusion safety and potential curative properties of ex-vivo expanded γδ T cells obtained from the same donor for patients who have hematological malignancies and have accepted allogeneic hematopoietic stem cell transplantation.

Detailed Description
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This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of ex-vivo expanded γδ T cell in patients with hematological malignancies after allogeneic hematopoietic stem cell transplantation. γδ T cell will be separated from peripheral blood of the same donors. After expansion in vitro, they will be infused to the patients as an immunotherapy treatment.

Official Title
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Safety and Efficiency of γδ T Cell Against Hematological Malignancies After Allo-HSCT. A Dose Escalation, Open-label, Phase 1/2 Study.

Conditions
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Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, Lymphoma

Intervention / Treatment
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* Biological: Ex-vivo expanded γδ T cell infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with hematological malignancies after allogeneic hematopoietic stem cell transplantation； Age criteria: 18-65 years; Weight criteria: > 40kg; Organ function criteria: Cardiac function: Left ventricular ejection fraction (LVEF) ≥40%, Pulmonary function: Indoor oxygen saturation≥95%, Alanine aminotransferase and aspartate aminotransferase ≤ 2.5×ULN (upper limit of normal value), Total bilirubin ≤ 1.5×ULN, Serum creatinine ≤ 1.5×ULN; Life expectancy of at least 4 months; ECOG (Eastern Cooperative Oncology Group) score ≤ 2; Patients able to understand and sign written informed consent. Exclusion Criteria: GVHD (graft versus host disease) ≥ grade Ⅱ； Thrombotic microangiopathy； Posttransplant lymphoproliferative disorders； Uncontrolled infection or other uncontrolled medical or psychiatric disorders which may preclude patients to undergo clinical studies (discretion of the attending physician)； Patients with chronic diseases that require treatment with immune agents or hormones; Suffering from systemic autoimmune disease or immunodeficiency disease; Systemic use of steroids; Allergic constitution; Hemorrhagic disease or coagulation disorders; Patients participating in other clinical trials within 30 days prior to enrollment; Patients receiving radiotherapy within 4 weeks prior to enrollment; Pregnant or breastfeeding women; According to the researcher's judgment, the patient has other unsuitable conditions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Interventional Model Description: This dose escalation study will be conducted in two phases. The first phase will have 3 cohorts(Dose escalation, x5 dose increments between cohorts, 2×10^6、 1×10^7/kg and 5×10^7 of cells per kg of body weight). The second phase is an expansion cohort at the maximum tolerated dose determined in the first phase.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with hematological malignancies after allo-HSCT<br>Patients with negative minimal residual disease or stable disease: After inclusion, patients will receive or not receive chemotherapy. Subsequently, patients will be dosed with γδ T cell. Patients with positive minimal residual disease but not hematologic relapse: After inclusion, patients will receive chemotherapy. Subsequently, patients will be dosed with γδ T cell. Patients with hematologic relapse: After inclusion, patients will receive chemotherapy. Subsequently, patients will be dosed with γδ T cell. | Biological: Ex-vivo expanded γδ T cell infusion<br>* Phase 1: Patients receive ex-vivo expanded γδ T cell (Dose escalation, 3 cohorts, x5 dose increments between cohorts, 2×10^6、 1×10^7 and 5×10^7 of cells per kg of body weight). Phase 2: Patients receive ex-vivo expanded γδ T cell at the maximum tolerated dose determined in Phase 1.<br>* Other names: Chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (AEs)[Safety] | Safety of γδ T cell assessed by incidence of treatment-emergent adverse events (AEs) per patient graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | Day 28 after completion of treatment | 
| Incidence of Dose-Limiting Toxicities (DLTs) [Tolerability] | Tolerability of γδ T cell assessed by incidence of dose-limiting toxicities (DLTs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | Day 28 after completion of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients reaching Complete Remission (CR) [Efficacy] | Efficacy of ex-vivo expanded γδ T cell assessed by number of patients reaching Complete Remission (CR). | 12 months post-treatment | 
| Overall Survival (OS) [Efficacy] | Efficacy of ex-vivo expanded γδ T cell assessed by overall survival (OS) measured in months. | 12 months post-treatment | 
| Quality of Life (QoL) | Quality of life determined by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 'C30'. | 12 months post-treatment | 
| Persistence of γδ T cell | Persistence of γδ T cell assessed by number in peripheral blood. | Before treatment and up to 3 months after treatment |