Multi-institutional Prospective Phase I Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies

Description

This Phase I dose-escalation trial is designed to evaluate the safety of administering rapidly -generated tumor multi-antigen associated -specific cytotoxic T lymphocytes, to HSCT recipients (Arm A) or future HSCT recipients (Arm B) for the treatment of high-risk or relapsed or refractory hematopoietic malignancies. In addition to safety, this study will also evaluate if event-free survival (EFS) is improved with TAA-T administration at six months after HSCT for patients with high risk AML and MDS (Arm C).This Phase I dose-escalation trial is designed to evaluate the safety of administering rapidly -generated tumor multi-antigen associated -specific cytotoxic T lymphocytes, to HSCT recipients (Arm A) or future HSCT recipients (Arm B) for the treatment of high-risk or relapsed or refractory hematopoietic malignancies. In addition to safety, this study will also evaluate if event-free survival (EFS) is improved with TAA-T administration at six months after HSCT for patients with high ris

Trial Eligibility

Recipient procurement Inclusion criteria: * Aged 6 months to 80 years * Received prior or anticipated myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant * Patients (Arm A) who have undergone allo-HSCT with high risk or relapse or residual/recurrent disease (see below) OR patients (Arm B) with high risk or relapsed/refractory disease (\> 2 regimens with greater than M1 marrow or persistent HD) with anticipated allo-HSCT: * Acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML), Ambiguous lineage leukemia or lymphoma, Chronic Myelogenous leukemia (CML), CMML, MDS: * Evidence of active leukemia or lymphoma disease by flow cytometry, morphology, or cytogenetic evaluation within the marrow or extramedullary sites. * Hodgkin's Lymphoma that has failed or are intolerant of Brentuximab, Non-Hodgkin Lymphoma (NHL) including Grey Zone Lymphoma, Anaplastic large cell lymphoma (ALCL), and mantle cell lymphoma: * Evidence of lymphoma by morphology, Positron Emission Tomography (PET)/ Computed tomography (CT) uptake in a site of previous disease in the absence of other etiologies. * ARM C only includes patients with high risk AML and MDS who have received an allo-HSCT and have not had hematologic relapse of disease. * Karnofsky/Lansky score of ≥ 50 * Agree to use contraceptive measures during study protocol participation (when age appropriate) * Patient or parent/guardian capable of providing informed consent. * T cell chimerism \> 94% if collected from recipient of allo-HSCT (performed within the last 6 months) * If the product is procured from the recipient in the autologous (Arm B) setting, the absolute lymphocyte count should be greater than or equal to 600 for procurement. Please note: If a patient has already undergone an allogeneic HSCT, it is NOT allowed to generate TAA-T from patient blood collected post-HSCT under Arm A or C Recipient Procurement Exclusion Criteria: * Patients with uncontrolled infections * Current evidence of GVHD \> grade 2 or bronchiolitis obliterans syndrome, sclerotic GVHD, or serositis Pregnancy or lactating (female of childbearing potential) Recipient Inclusion criteria for initial TAA-T administration and for subsequent infusions * Patients (Arm A) who have undergone allo-HSCT with high risk or relapse or residual/recurrent disease (see below) OR patients (Arm B) with high risk or relapsed/refractory disease (\> 2 regimens with greater than M1 marrow or persistent HD) with anticipated allo-HSCT: o Acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML), Ambiguous lineage leukemia or lymphoma, Chronic Myelogenous leukemia (CML), CMML, MDS: Evidence of active leukemia or lymphoma disease by flow cytometry, morphology, or cytogenetic evaluation within the marrow or extramedullary sites. o Hodgkin's Lymphoma that has failed or are intolerant of Brentuximab, NHL including Grey Zone Lymphoma, ALCL, and mantle cell lymphoma: Evidence of lymphoma by morphology, PET/CT uptake in a site of previous disease in the absence of other etiologies. o ARM C only includes patients with high risk AML and MDS who have received an allo-HSCT and have not had hematologic relapse of disease. * Steroids less than 0.5 mg/kg/day prednisone or equivalent. * Karnofsky/Lansky score of ≥ 50. * Bilirubin \< 2.5 mg/dL, AST/ALT \<5x upper limit of normal, Serum creatinine \< 1.0 or 2x the upper limit of normal (whichever is higher). * Pulse oximetry of \> 90% on room air. * Absolute neutrophil count \> 250/ µL (may be supported with Granulocyte colony-stimulating factor (GCSF)). * Agree to use contraceptive measures during study protocol participation (when age appropriate). * Patient or parent/guardian capable of providing informed consent. * LVEF \> 50% or LVSF \> 27% (performed within the last 6 months) if history of TBI \>500 cGy for arm A and B. * Total chimerism \> 50%; or if cancer cells preclude this, donor T cell chimerism \> 50% (performed within the last 6 months). Recipient Exclusion criteria for initial and subsequent TAA-T infusions * Patients who received ATG, Campath, or other T cell immunosuppressive monoclonal antibodies within 28 days prior to TAA-T infusion. * No investigational therapies (under IND, not extensively studied in the current clinical context) within 28 days prior to TAA-T infusion. For allogeneic HSCT recipients PD-1 inhibitors or other T cell activating agents will be excluded. For Arm B, if the patient has tolerated these agents without autoimmunity, these may be continued with the TAA-T infusion. * Uncontrolled infections * Active Bronchiolitis obliterans syndrome, sclerotic GVHD, or serositis * Current evidence of GVHD \> grade 2 for Arm A and B; Active GVHD of any grade is exclusion for arm C patients. * Pregnancy or lactating (female of childbearing potential)

Study Info

Interventions

Locations Recruiting

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