Vactosertib in Combination w/ Pomalidomide in Relapsed or Relapsed and Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT03143985|
Recruitment Status : Recruiting
First Posted : May 8, 2017
Last Update Posted : July 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Vactosertib Drug: Pomalidomide||Phase 1|
- 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
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)
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b Trial of Vactosertib in Combination With Pomalidomide (POM) in Relapsed or Relapsed and Refractory Multiple Myeloma (RRMM)|
|Actual Study Start Date :||July 21, 2017|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2020|
Experimental: Vactosertib + Pomalidomide
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.
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
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
Other Name: POM
- 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 [ Time Frame: Up to 30 days after treatment ends (24 weeks + 30 days) ]the largest tested dose where multiple dose limiting toxicities are not observed
- Overall response rate [ Time Frame: Up to 6 months after beginning treatment ]overall response is the complete response [CR] + very good partial response [VGPR] + partial response [PR] based on International Myeloma Working Group (IMWG) defined response criteria
- Progression-free survival (PFS) [ Time Frame: Up to 30 days after discontinuation of treatment ]Progression-free survival will be measured from study entry to progression or death of any cause, whichever comes first.
- Progression-free survival at 6 months (PFS-6) [ Time Frame: Up to 6 months after beginning treatment ]Number of patients who did not progress on treatment, at 6 months after beginning treatment
- Duration of Response [ Time Frame: Up to 6 months after beginning treatment ]The time from the first confirmed response to progression of disease. Responses include Complete Response (CR), Stringent CR, Very Good Partial Response, Partial Response, Minor Response, Stable disease. Responses based on International Myeloma Working Group (IMWG) defined response criteria
- clinical benefit rate [ Time Frame: Up to 6 months after beginning treatment ]clinical benefit rate is the CR + VGPR + PR + minimal response [MR] based on International Myeloma Working Group (IMWG) defined response criteria
- Overall Survival [ Time Frame: Up to 6 months after progression ]Overall survival for all will be measured from study entry to death from any cause
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03143985
|Contact: Ehsan Malek, MD||216-286-4441||Ehsan.Malek@Uhhospitals.org|
|United States, Ohio|
|University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Ehsan Malek, MD 216-844-0139 firstname.lastname@example.org|
|Principal Investigator: Ehsan Malek, MD|
|Cleveland Clinic, Case Comprehensive Cancer Center||Withdrawn|
|Cleveland, Ohio, United States, 44915|
|Principal Investigator:||Ehsan Malek, MD||University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|