NCT02203903

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

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Catherine Bollard · Academic / Other
• Sex: All
• Age: 6 Months – 80 Years
• Healthy volunteers: Not accepted

Summary

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 with high risk AML and MDS.

Detailed description

Patients with evidence of high-risk or relapsed or persistent hematopoietic malignancies (for example but not limited to: acute myeloid leukemia and myelodysplastic syndrome (MDS)) will be eligible for this study. Patients with high risk for relapse will be eligible to receive planned infusion of allogeneic TAA-T after HSCT (with high risk AML and MDS who have undergone allo-HSCT and are in a hematologic remission). We will utilize our established protocol for the manufacture of tumor multi-antigen associated specific cytotoxic T lymphocytes. Peripheral blood mononuclear cells will be exposed to antigen presenting cells pulsed with peptides to tumor antigens (PRAME, WT1, Survivin) in a cytokine milieu favorable to T cell expansion/activation, inducing selective expansion of T cells targeted to kill tumor cells. Patients would be monitored for the development of toxicity. In patients with disease at the time of TAA-T infusion, efficacy would be evaluated as a secondary endpoint using standard criteria. Exploratory investigational analyses would include monitoring of cytokine and cellular milieu pre- and post- TAA-T infusion and in vitro characterization of the host tumor, donor lymphocyte product, and TAA-T product. TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30, whichever comes first at dose level 4 . Infusions will be within first 5 months post-HSCT. Patients will receive a TAA-T cell dose of 4 x 107 cells/m2. Each patient will receive at least one infusion according to the enrolled dose level, where the expected volume of infusion is 1 to 10 cc. If patients with active disease (defined as MRD+ at the time of TAA-T infusion) do not have ≥ grade 3 toxicity that is possibly, probably, or definitely attributed to TAA-T infusion and fail to rapidly progress with disease requiring urgent therapy, patients may receive a subsequent TAA-T cell dose (infusion #2). A subsequent dose (infusion #2) will also be available for those patients who have stable disease or a mixed, partial, or complete response (including continued complete response) by the International Working Group (IWG) criteria (see section 4.2.1) at the evaluation after the first TAA-T infusion. Patients who have received at least 2 infusions of TAA-T are eligible to receive up to 6 additional doses (infusion #3 to #8) of TAA-T at monthly intervals each of which will consist of the same cell number as their enrolled dose level. Patients will not be able to receive additional doses until the initial safety profile is completed at 28 days following the second infusion. Notably, these doses will be identical to the treated dose for this patient (i.e. no subsequent dose escalation). Patients would then receive additional doses starting greater than 28 days from second infusion and be treated at the same dose level as he/she has previously received.

Conditions

• Relapsed/Refractory Hematopoietic Malignancies, Acute Myeloid Leukemia and MDS

Interventions

Type	Name	Description
BIOLOGICAL	Tumor associated antigen lymphocytes (TAA-T)	TAA-T may be generated from donors or recipients and will be tested for specificity to 3 tumor antigens commonly found in hematological malignancies (WT1, PRAME, and SURVIVIN,). The goal of this cell infusion will be to initiate an immune response to residual leukemia or lymphoma that includes multiple antigens and may prevent tumor evasion (through decreased expression of a single antigen).

Timeline

• Start date: 2015-01-01
• Primary completion: 2026-11-30
• Completion: 2027-06-28
• First posted: 2014-07-30
• Last updated: 2025-05-31

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study