NCT03143985

Vactosertib in Combination w/ Pomalidomide in Relapsed or Relapsed and Refractory Multiple Myeloma

A Phase 1b Trial of Vactosertib in Combination With Pomalidomide (POM) in Relapsed or Relapsed and Refractory Multiple Myeloma (RRMM)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Koen van Besien · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to see if the study drug, called Vactosertib, is safe and determine what the best dose is to treat future patients when given in combination with pomalidomide (POM). The study will also look to see if it has any effect on multiple myeloma, when given in combination with POM.

Detailed description

Primary Objective * To determine the maximum tolerated dose (MTD) or maximum tested dose level of Vactosertib given in combination with pomalidomide (POM) for the treatment of relapsed or relapsed or refractory multiple myeloma (RRMM) * To characterize the safety and tolerability profile of Vactosertib in combination with POM at the MTD Secondary Objectives To evaluate the activity of the combination of Vactosertib/POM regimen in terms of: * Overall response rate (complete response \[CR\] + very good partial response \[VGPR\] +partial response \[PR\]) and clinical benefit rate (CR + VGPR + PR + minimal response \[MR\]) based on International Myeloma Working Group (IMWG) defined response criteria and the duration of response (DOR) in RRMM patients. * Progression-free survival (PFS) and PFS at 6 months (PFS-6) Exploratory Objective: To evaluate the bone remodeling and immunologic effects of POM/Vactosertib combination therapy and its correlation with clinical outcome in patients with multiple myeloma. Study Design To evaluate the bone remodeling and immunologic effects of POM/Vactosertib combination therapy and its correlation with clinical outcome in patients with multiple myeloma. This study is a Phase I, open label trial of Vactosertib in combination with standard doses of POM. The study will be conducted as a modified Fibonacci 3 + 3 dose escalation design to determine the MTD of Vactosertib in combination with standard doses of POM. Patients will receive combination Vactosertib/POM.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Vactosertib	Vactosertib is an inhibitor of protein serine/threonine kinase activity of TGF-β receptor type 1 (TGFBR1; ALK5). Vactosertib inhibits the phosphorylation of the ALK5 substrates, Smad2 and Smad3, and the intracellular signaling of TGF-β. Dosing begins at 60mg by mouth, daily and may increase to 240mg by mouth daily in the absence of dose limiting toxicities
DRUG	Pomalidomide	POM, an analog of thalidomide, is an immunomodulatory agent with antineoplastic activity. Myeloma tumor cells exposed to POM, undergo growth arrest and increased apoptotic cell death. POM enhances T cell- and natural killer cell-mediated immunity and inhibit production of pro-inflammatory cytokines by monocytes. POM may be taken orally with water. Capsules should not be broken, chewed or opened. POM should be taken without food (at least 2 hours before or 2 hours after a meal). POM will be commercially available. POM will be taken by mouth at a dose of 4mg per day

Timeline

• Start date: 2017-07-21
• Primary completion: 2022-02-27
• Completion: 2022-09-01
• First posted: 2017-05-08
• Last updated: 2024-05-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study