Relapse remains the leading cause of treatment failure for 30–50% of patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic blood or marrow transplantation (BMT). Safety and relapse risk reduction with an ex vivo-expanded, donor-derived, haploidentical (haplo) natural killer (NK)-cell infusion in conjunction with haploBMT were reported by investigators at MD Anderson Cancer Center in a phase I study (Ciurea, Blood 2017). These data support investigation of CSTD002, haplo NK cells expanded ex vivo using plasma membrane nanoparticles bearing membrane-bound IL-21 and 4-1BBL. This study represents a public–private partnership between the sponsor (Kiadis Pharma) and the Blood and Marrow Transplant Clinical Trials Network (BMT CTN), leveraging existing National Institutes of Health-supported clinical trials infrastructure to conduct the trial.

BMT CTN 1803 is a phase II, single-arm, open-label, multicenter trial designed to investigate the safety and efficacy of CSTD002 for the treatment of patients with high-risk AML or MDS undergoing haploBMT.

An initial safety run-in phase will precede enrollment into the full study of approximately 60 patients.

Donor peripheral blood will be drawn to start the NK-cell expansion approx. 5 weeks before the planned haploBMT. Patients will receive melphalan 140 mg/m² IV (100 mg/m² for patients ≥60 years old) on Day -7; fludarabine 40 mg/m² IV on Days -7, -6, -5, and -4; and 2 Gy of total body irradiation on Day -3. Donor bone marrow will be harvested and given on Day 0. Three doses of CSTD002 will be administered IV on Days -2, +7, and +28, relative to the haploBMT. The recommended dose of CSTD002 for administration will be formulated at 1 × 10⁸ NK cells/kg of recipient body weight. Graft-versus-host disease (GVHD) prophylaxis is post-transplantation cyclophosphamide with tacrolimus and mycophenolate mofetil.

The primary endpoint is cumulative incidence of relapse at 1 year post haploBMT in patients receiving at least 1 infusion of CSTD002. Secondary endpoints are safety and tolerability of CSTD002; overall survival; non-relapse mortality; relapse-free survival; GVHD-free survival; cumulative incidence of acute GVHD and chronic GVHD; hematologic recovery; donor-cell engraftment; primary and secondary graft failure; overall incidence of toxicity; and cumulative incidence of infections including cytomegalovirus re-activation and symptomatic BK virus hemorrhagic cystitis. Exploratory endpoints are systemic immunosuppression-free survival; immune reconstitution at Days 28, 100, and 365 post haploBMT; proportion of patients with detectable minimal residual disease at Days 28 and 100 post haploBMT; feasibility of administering the planned CSTD002 doses; and impact of NK-cell alloreactivity on relapse and survival.