NCT04284228

Antigen-specific T Cell Therapy for AML or MDS Patients With Relapsed Disease After Allo-HCT

A Phase 1 / 2 Study to Evaluate the Safety, Tolerability and Initial Anti-Tumor Activity of Adoptively Transferred T Lymphocytes Targeting WT1, PRAME and Cyclin A1 AML or MDS Patients With Relapsed Disease After Matched Allogeneic HCT

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 22 (estimated)
• Sponsor: NexImmune Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This Research study is being done to characterize the safety, tolerability, and preliminary antitumor activity of the NEXI-001 T cell product (a new experimental therapy), which contains populations of CD8+ T cells targeting multiple leukemia associated antigen peptides in patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) who have relapsed disease after an allogeneic hematopoietic cell transplant (HCT). The study will enroll AML or MDS patients who have either Minimal Residual Disease (MRD) or relapsed disease after a human leukocyte antigen (HLA)-matched allogeneic HCT. Patients who have had an HLA-mismatched or haploidentical allogeneic HCT will not be eligible to participate in this study. Eligible patients for this study must also have ≥ 50% T-cell chimerism from the original donor at the time study entry. The enrolled patients will undergo bridging therapy for the purposes of disease control while the NEXI-001 T cell product is being manufactured. Choice of bridging therapy administered will be per the Investigator's discretion, but is limited to acceptable agents as specified in the protocol. Bridging therapy will be administered prior to lymphodepleting (LD) therapy, with the last dose of the bridging therapy administered ≥ 14 days prior to initiation of LD therapy. Within 72 hours after completing LD therapy, patients will receive a single IV infusion of the NEXI-001 T cell product.

Detailed description

The NEXI-001 is an adoptive cellular therapy product which contains populations of antigen-specific CD8+ T cells. The antigen-specific CD8+ T cells in the NEXI-001 T cell product are derived from Peripheral Blood Mononuclear Cells (PBMC) obtained from the original stem cell donor. During the manufacturing process, these cells are primed and expanded ex vivo using nano-size artificial Antigen Presenting Cells (aAPC) loaded with five leukemia associated antigen peptides in combination with a proprietary T cell enrichment and expansion process. The NEXI-001 T cell product is restricted to patients that are HLA-A2.01 allele positive for this study. There are two parts to this study, a Safety Evaluation Phase and a Dose Expansion Phase. The Safety Evaluation Phase will determine the safety and tolerability of a single dose of NEXI-001 T cell product, and will consist of Dose Escalation at two dose levels - each with cohorts of three patients. When all three patients at Dose Level 1 have dosed and cleared the DLT period, three additional patients will be enrolled at Dose Level 2. When three patients have cleared the DLT period at the highest dose level, that dose will be advanced to the Dose Expansion Phase. The Dose Expansion Phase will enroll up to 16 additional patients to further define the safety and evaluate the initial anti-tumor efficacy of the NEXI- 001 T cell product at the dose established from the Safety Evaluation Phase. All patients will enter a Post-Treatment Follow-Up period after infusion of the NEXI- 001 T cell product. During this phase, all patients will be monitored for AEs and followed for anti-leukemia response until the end of study visit is complete (up to one year). Additional assessments for safety, disease status, and other secondary and exploratory endpoints will also be monitored during the follow-up period. All patients will be followed for overall survival (OS) from time of disease progression until the last visit of the last patient. During this time, patients will be followed via telephone or other electronic contact at 12 week intervals for monitoring of OS.

Conditions

• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndrome (MDS)

Interventions

Type	Name	Description
BIOLOGICAL	Infusion of NEXI-001 T Cells	Procedure: A single IV infusion of NEXI-001 T Cells at Day 1 after Lymphodepletion(LD) Therapy. At dose Level 1: 1.0 x 108 total viable T cells At dose Level 2: 2.0 x 108 total viable T cells Procedure: Lymphodepletion: IV administration of fludarabine 30 mg/2 and cyclophosphamide 300 mg/m2 for 3 days. lymphodepletion (LD) Therapy: Subjects will received bridging therapy agents during lymphodepletion for 3 consecutive days prior to receiving the NEXI-001 product Drug: Fludarabine Fludarabine infusion Other Name: Fludarabine monophosphate Drug: Cyclophosphamide Cyclophosphamide infusion Other Name: Cytoxan

Timeline

• Start date: 2020-02-20
• Primary completion: 2024-10-01
• Completion: 2025-03-01
• First posted: 2020-02-25
• Last updated: 2024-01-16

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study