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

NCT03143985 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CASE1A17
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Keywords

Vactosertib; Pomalidomide

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose (MTD) or maximum tested dose level of Vactosertib given in combination with POM for the treatment of relapsed or RRMM

  the largest tested dose where multiple dose limiting toxicities are not observed

  Up to 30 days after treatment ends (24 weeks + 30 days)

Secondary Outcomes (6)

• Overall response rate

  Up to 6 months after beginning treatment

• Progression-free survival (PFS)

  Up to 30 days after discontinuation of treatment

• Progression-free survival at 6 months (PFS-6)

  Up to 6 months after beginning treatment

• Duration of Response

  Up to 6 months after beginning treatment

• clinical benefit rate

  Up to 6 months after beginning treatment

Study Arms (1)

Vactosertib + Pomalidomide

EXPERIMENTAL

Vactosertib tablets, taken once daily for the first and second dose levels and twice a day for third and fourth dose level levels for 5 days followed by 2 days without treatment, repeated for 28-day cycles until evidence of progressive disease, intolerable toxicity, or participant discontinuation. For dose escalation - dosing initiated at 60 mg once daily by oral administration and will be increased to determine MTD. Provisional subsequent doses are 60, 120, once daily and 100 mg and 200 mg twice daily on days 1-5, 8-12, 15-19 and 22-26. Extension cohorts will enter at 200 mg twice daily (i.e. if MTD not defined) for 12 months until progression or intolerable toxicity. POM is administered orally (4 mg/day daily on Days 1 - 21 days). Treatment will occur in a suitable outpatient ambulatory care setting that is equipped for monitoring of patients with hematopoietic malignancies undergoing early clinical trial research.

Drug: Vactosertib; Drug: Pomalidomide

Interventions

Vactosertib DRUG

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

Also known as: TEW-7197, EW7197, EW-7197

Vactosertib + Pomalidomide

Pomalidomide DRUG

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

Also known as: POM

Vactosertib + Pomalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has given voluntary written informed consent before performance of any study-related procedures not part of standard (non-investigational) medical care.
• Patient has been previously diagnosed with multiple myeloma based on standard criteria.
• Patient has relapsed or refractory disease according to international uniform response criteria and must have previously received therapy with:
• A proteasome inhibitor and Immunomodulatory imide drugs (IMiD)
• All subjects must have documented disease progression during or after their last antimyeloma therapy.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2.
• Patient has measurable disease defined as at least one of the following:
• Serum M protein ≥ 0.5 /dL (≥5 g/L)
• Urine M protein ≥ 200 mg/24 hours
• Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65)
• Absolute neutrophil count (ANC) ≥ 1000 cells/μl (growth factor cannot be used within the previous 5 days)
• Platelet count ≥ 50,000/μl (without platelet transfusion in the previous 5 days)
• Aspartate aminotransferase (AST/SGOT) and Alanine aminotransferase (ALT/SGPT) ≤ 3.0 x upper limit of normal (ULN)
• Serum total bilirubin ≤ 2.0 mg/dL or \>3.0 x ULN for subjects with hereditary benign hyperbilirubinemia
• Creatinine clearance ≥ 30 ml/min (calculated by the Cockcroft-Gault Equation or per 24 hour urine collection)

You may not qualify if:

• Prior therapy with Vactosertib or received any investigational drug within the prior 28 days.
• Plasma Cell Leukemia
• Patients with solitary plasmacytoma
• Patients who are primarily eligible for autologous stem cell transplant
• Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and immunotherapy) within the prior 21 days except for alkylating agents (e.g., melphalan) within the prior 28 days.
• Prior treatment with pomalidomide.
• Subjects with active malignancy and/or cancer history that may confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) with substantial potential for recurrence and/or ongoing active malignancy must be discussed with the trial collaborator, MedPacto Inc., before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including superficial bladder cancer), cervical intraepithelial neoplasia, and organ-confined prostate cancer with no evidence of progressive disease
• Any \> grade 1 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTC AE) v.4.03) adverse reaction unresolved from previous treatments or not readily managed and controlled with supportive care. The presence of alopecia of any grade and peripheral neuropathy ≤ Grade 2 without pain is allowed.
• Previous allogeneic stem cell transplantation with active graft versus host disease (GVHD), or treatment with immunosuppressive therapy in the 2 months prior to study entry.
• No oral corticosteroids 3 days before initiating combinations Vactosertib/POM; inhaled corticosteroids are permitted.
• Patient is known to be human immunodeficiency virus (HIV) positive, or have chronic or active Hepatitis B (core- or surface antigen-positive) or active hepatitis C infection.
• Clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association (NYHA) Class 3 or 4, congestive heart failure, uncontrolled or unstable angina, history of myocardial infarction or stroke within 6 months prior to study entry, or clinically significant arrhythmias not controlled by medication).
• Major abnormalities identified by ECG or echocardiogram (ECHO), at the Investigator's discretion.
• Presence of aneurisms of the ascending aorta or aortic stress.
• Hypertension that is not controlled by standard medication (to 150/90 mmHg or below).

Sponsors & Collaborators

• Koen van Besien: lead

Study Sites (1)

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• Malek E, Rana PS, Swamydas M, Daunov M, Miyagi M, Murphy E, Ignatz-Hoover JJ, Metheny L, Kim SJ, Driscoll JJ. The TGFbeta type I receptor kinase inhibitor vactosertib in combination with pomalidomide in relapsed/refractory multiple myeloma: a phase 1b trial. Nat Commun. 2024 Aug 27;15(1):7388. doi: 10.1038/s41467-024-51442-2.

  PMID: 39191755 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

vactosertib; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Koen van Besien, MD, PhD

  University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 4, 2017
• First Posted: May 8, 2017
• Study Start: July 21, 2017
• Primary Completion: February 27, 2022
• Study Completion: September 1, 2022
• Last Updated: May 24, 2024

Record last verified: 2024-05

Locations

US (1)