NCT05447663

A Study of Siremadlin Alone and in Combination With Donor Lymphocyte Infusion in Acute Myeloid Leukemia Post-allogeneic Stem Cell Transplant

A Phase Ib/II, Open Label Study of Siremadlin Monotherapy and in Combination With Donor Lymphocyte Infusion as a Treatment for Patients With Acute Myeloid Leukemia Post-allogeneic Stem Cell Transplantation Who Are in Complete Remission But at High Risk for Relapse.

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to confirm a safe dose and schedule as well as the preliminary efficacy of siremadlin alone, and in combination with donor lymphocyte infusion (DLI), in adult participants with Acute Myeloid Leukemia (AML) who were in remission following allogeneic stem cell transplantation (allo-SCT) but were at high risk for relapse based on the presence of pre-transplant risk factors.

Detailed description

This is a Phase Ib/II, single arm, open label, multi-center study of siremadlin as monotherapy and in combination with DLI, in adult participants with AML. The primary purpose of the study was to confirm the safe dose and schedule of siremadlin monotherapy and in combination with DLI. The study is also designed to assess the preliminary efficacy in preventing hematologic relapse. The study was initially planned to enroll approximately 38 participants starting with a dose confirmation of siremadlin monotherapy (part 1) to determine the siremadlin recommended dose, followed by a treatment strategy of siremadlin/DLI (Part 2). After enrolling 8 participants (at the starting dose 30 mg/day on days 1-5 of a 28-day treatment cycle) in part 1, Novartis took the decision to put the enrollment in permanent halt and terminate the siremadlin program. For that reason, the enrollment in part 2 will not be open. The Novartis decision was not driven by any safety concerns. In part 1 approximately 12 participants were planned to be enrolled in 2 cohorts (starting dose 30 mg/day on days 1-5 of a 28-day treatment cycle, dose level +1 at 40 mg/day and dose level -1 at 20 mg/day) and participants were planned to be treated for a maximum of 24 cycles. In part 2, participants were planned to follow a treatment strategy, which contains three consecutive phases for a maximum of 24 cycles in total: * A priming phase with siremadlin monotherapy at the recommended dose determined in Part 1 (for at least 2 cycles). Participants who were not eligible for the combination phase of siremadlin/DLI could continue priming phase with siremadlin monotherapy. * A combination phase of siremadlin in combination with DLI (siremadlin/DLI) for participants who were eligible to receive DLI (up to a total of 3 combination cycles). * A maintenance phase with siremadlin monotherapy.

Conditions

• Acute Myeloid Leukemia
• Allogeneic Stem Cell Transplantation

Interventions

Type	Name	Description
DRUG	Siremadlin	Siremadlin was administered at a starting dose of 30 mg/day on days 1-5 of a 28-day treatment cycle (Part 1).

Timeline

• Start date: 2023-02-23
• Primary completion: 2023-10-26
• Completion: 2023-10-26
• First posted: 2022-07-07
• Last updated: 2025-05-16
• Results posted: 2025-01-14

Locations

6 sites across 3 countries: Germany, Italy, Spain

Regulatory

• FDA-regulated drug study