Mirdametinib + Sirolimus for Multiple Myeloma

Recruiting in Palo Alto (17 mi)

Overseen byElizabeth M Hill, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?Background: Multiple myeloma (MM) is a type of blood cancer that affects a person s immunity. MM returns after treatment (relapse) in almost all people; MM may also not respond to initial treatment (refractory). Many people with relapsed refractory MM (RRMM) also have changes in their KRAS and NRAS genes. Researchers want to try a new drug treatment that targets cancer with these changed genes. Objective: To test 2 drugs (mirdametinib and sirolimus) in people with RRMM. Eligibility: People aged 18 and older with RRMM who have changes in their KRAS or NRAS genes. Design: Participants will be screened. They will have blood tests and imaging scans. They will have an eye exam and a test of their heart function. They will need to provide proof of their disease status and of their KRAS or NRAS status. If neither is available, the tests will be repeated. Participants will have a bone marrow biopsy: A needle will be inserted into a hipbone to draw out some soft tissue. This study will be done in two parts. In the first part of this study, we will find a safe dose of mirdametinib combined with sirolimus. In the second part, we will learn more about how mirdametinib combined with sirolimus may work against RRMM. Mirdametinib (capsules) and sirolimus (tablets) are taken by mouth. Participants will take both drugs at home on a 4-week cycle. They will take mirdametinib twice a day for the first 3 weeks of each cycle. They will take sirolimus once a day, every day, during each cycle. Participants will have study visits once a week during the first cycle, and then on the first day of subsequent cycles. Blood, heart, imaging scans, and other tests will be repeated. Treatment with the study drugs will go on for 1 year. Then participants will have follow-up visits every 3 months for 4 more years.

Eligibility Criteria

This trial is for adults over 18 with relapsed refractory multiple myeloma (RRMM) who have specific genetic changes (KRAS or NRAS mutations). Participants must provide proof of their disease and mutation status, undergo various screenings including blood tests, imaging scans, an eye exam, heart function test, and a bone marrow biopsy.

Inclusion Criteria

Participants must have measurable disease per International Myeloma Working Group (IMWG) criteria

Participants must agree to use contraception as specified if of childbearing potential or able to father a child

Participants seropositive for HIV, HCV, or HBV must meet specific criteria related to their infection status

+7 more

Exclusion Criteria

Positive beta-HCG serum or urine pregnancy test performed in IOCBP at screening

I haven't taken certain medications or substances in the last 14 days.

Participant has abnormal QT interval corrected by Fridericia's formula

+6 more

Participant Groups

The study is testing the combination of two oral drugs: mirdametinib (capsules) taken twice daily for three weeks in a four-week cycle and sirolimus (tablets) taken once daily throughout the cycle. The first part determines a safe dosage; the second part assesses effectiveness against RRMM.

2Treatment groups

Experimental Treatment

Group I: Arm 2Experimental Treatment2 Interventions

Sirolimus and RP2D of mirdametinib

Group II: Arm 1Experimental Treatment2 Interventions

Sirolimus and escalating doses of mirdametinib