NCT05744739

Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)

Phase 1 Dose Escalation Study of Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase 1 of the study will open first with a (Bayesian optimal interval BOIN) dose finding design. The starting dose of tomivosertib is 100mgdaily (doses 24 ± 2 hours apart), PO, self-administered with meals. The dose finding follows a BOIN design, with the 100mg BID dose level with a meal being the highest dose. There is one dose level below (dose level -1 = 100mg QD without a meal) that will be given if the de-escalation condition is met during dose finding. Upon completion of the phase 1 dose finding portion of the study, the recommended starting dose of tomivosertib for the subsequent combination with the other agents will be determined, as described in Section 4.3 and Section 8.0. Tomivosertib will be dosed continuously on days 1-28 of each 28-day cycle at the dose level assigned for that cohort.

Detailed description

PRIMARY OBJECTIVE: To determine the dose of maximum pharmacologic activity (MPA) of tomivosertib in relapsed/refractory AML . SECONDARY OBJECTIVES: 1. To assess the adverse event profile of tomivosertib 2. To estimate the rate of complete remission (CR) 3. To estimate the rate of overall response 4. To estimate the duration of response (DOR) 5. To estimate progression free survival (PFS) 6. To estimate overall survival (OS) 7. To assess the outcomes for patients who undergo allogeneic hematopoietic stem cell transplant (HSCT) 8. To assess the pharmacodynamics of tomivosertib by eIF4E phosphorylation before, during, and after cycle 1 treatment 9. To measure MCL1 expression before and after cycle 1 treatment 10. To assess the steady-state pharmacokinetics of tomivosertib EXPLORATORY OBJECTIVES: 1. To correlate eIF4E phosphorylation before and after cycle 1 treatment with treatment response. 2. To correlate MCL1 expression before and after treatment with treatment response.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Tomivosertib	Given PO

Timeline

• Start date: 2023-09-29
• Primary completion: 2024-08-20
• Completion: 2030-04-23
• First posted: 2023-02-27
• Last updated: 2025-10-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study