Phase 2 Trial to Assess Clinical Efficacy in 45 Patients

NCT06529731, a multi-center Phase 2 trial led by the University of Pittsburgh Cancer Center, is recruiting 45 adult patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) following allogeneic hematopoietic stem cell transplantation. The trial commenced on September 23, 2024, and aims for a primary completion date of October 31, 2027, involving three U.S. centers in Pittsburgh, St. Louis, and Seattle. Actimmune will be administered subcutaneously three times a week for 12 weeks, with donor lymphocyte infusion (DLI) performed at week 4, and a second infusion may be administered at week 8. The primary endpoint is one-year event-free survival, designed to evaluate the durability of relapse prevention rather than short-term response.

Restoring Immune Surveillance in Leukemia by Activating IFNGR

Actimmune is a recombinant interferon gamma-1b that binds to interferon gamma receptors (IFNGR1 and IFNGR2), activating JAK1, JAK2, and STAT1 signaling. This process enhances the expression of major histocompatibility complex (MHC) and antigen presentation in leukemia cells, helping donor T cells recognize the tumor and amplifying the graft-versus-leukemia (GVL) effect of DLI. Researchers will apply single-cell RNA sequencing to pre- and post-treatment samples to track changes in the transcriptome, including leukemia cells with stem cell characteristics. If the association between response and biomarkers is confirmed, it will strengthen the basis for patient selection and subsequent prophylactic trials.

Repurposing an Approved Orphan Drug for Hematological Malignancies

Actimmune is a marketed drug approved by the U.S. FDA in 1990 for the reduction of serious infections in chronic granulomatous disease and the delay of progression of severe malignant osteopetrosis. Treatment of AML/MDS and relapsed disease post-transplant is not an approved indication, and this study is a Phase 2 trial. Amgen completed the acquisition of Horizon Therapeutics for $27.8 billion on October 6, 2023, and has acquired Actimmune, participating in this trial as a collaborating institution. The established manufacturing and safety data reduce development risk, but the management of acute and chronic graft-versus-host disease (GVHD) and myelosuppression in combination with DLI is critical to clinical value.

Competitive Benchmark: Azacitidine and Venetoclax-Based Salvage Therapy

In relapsed AML/MDS post-transplant, immunosuppressive agent reduction, DLI, demethylating agents such as azacitidine or decitabine, venetoclax combination, targeted mutation therapies, and secondary transplantation are used on a patient-by-patient basis. While DLI alone has been shown to induce remission in approximately 29% of patients with relapsed AML, tumor burden and GVHD limit its application. A competing clinical trial, NCT05226455, is evaluating venetoclax, azacitidine, and selective DLI, and the Actimmune combination must differentiate itself not only in terms of efficacy but also in terms of the balance between infection, hematological toxicity, and GVHD. The global AML treatment market is projected to grow from $3.1795 billion in 2023 to $6.2921 billion in 2030, and the MDS drug market is estimated at $4.6 billion, providing ample commercial potential for successful repurposing.