RECRUITING

Combination Therapy (Mirdametinib and Sirolimus) for RAS Mutated Relapsed Refractory Multiple Myeloma

Talk to us

Conditions

Multiple MyelomaRelapsed and/or Refractory Multiple Myeloma (RRMM)KRASNRAS

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 1b/2 Study of Combination Therapy (Mirdametinib and Sirolimus) for RAS Mutated Relapsed Refractory Multiple Myeloma (RRMM)

Quick Facts

Study Start:2025-06-17
Study Completion:2033-01-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06876142

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Participants must have a documented diagnosis of multiple myeloma (MM) defined by the International Myeloma Working Group (IMWG) Criteria. Participants at diagnosis must have had a history of the serum-M protein \>= 3 g/dL and or bone marrow plasma cells \>= 10% and the history of at least one of the following:
  2. * Anemia: hemoglobin \<= 10 g/dL or a 2g/dL decrease from the lower limit of normal,
  3. * Renal failure: creatinine clearance \< 40 ml/min, OR
  4. * Hypercalcemia: calcium (Ca) \>= 11 mg/dL OR \> 1 mg/dL higher than the upper limit of normal (ULN), OR
  5. * Lytic bone lesions on X-Ray, Computed Tomography (CT), or Positron Emission Tomography (PET)/CT, OR
  6. * \>= 2 focal lesions on spinal Magnetic Resonance Imaging (MRI), OR
  7. * \>= 60% bone marrow plasma cells, OR
  8. * Involved/un-involved serum-free light chain ratio \>= 100.
  9. * Participants must have measurable disease per International Myeloma Working Group (IMWG) criteria.
  10. * Participants must have relapsed and/or refractory multiple myeloma (RRMM) with "penta-class exposed" disease, as defined by previous therapy with an anti-CD38 monoclonal antibody, 2 immunomodulatory drugs \[IMiDs\], and 2 proteasome inhibitors \[Pis\]), 3 previous lines of therapy, and no other available options.
  11. * Participants must have a history of known somatic mutation in KRAS or NRAS. Note: For participants that come to NIH without confirmation of KRAS or NRAS, their status will be determined by the TSO500 NSR device.
  12. * Participants must be off other myeloma-directed therapy (except for radiation) for at least 14 days prior to the study treatment initiation.
  13. * Age \>= 18 years.
  14. * ECOG performance status \<= 2.
  15. * Participants must have adequate organ and marrow function as defined below:
  16. * Breastfeeding participants must be willing to discontinue breastfeeding after study treatment initiation.
  17. * Participants seropositive for human immunodeficiency virus (HIV) infection must:
  18. * be on anti-retroviral therapy; and
  19. * have the undetectable viral load.
  20. * Participants seropositive for Hepatitis C virus (HCV) infection must
  21. * have been treated and cured; or
  22. * if currently on treatment, have an undetectable HCV viral load.
  23. * Participants seropositive for Hepatitis B virus (HBV) infection must
  24. * be on suppressive therapy if necessary; and
  25. * have viral load \<100 IU/mL.
  26. * Ability of the participant to understand and the willingness to sign a written informed consent document.
  1. * Received any investigational agents within 14 days prior to the study treatment initiation.
  2. * Vaccinated with live, attenuated vaccines within 30 days prior to the study treatment initiation.
  3. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to mirdametinib and/or sirolimus.
  4. * Current diagnosis of plasma cell leukemia.
  5. * Current or history of amyloidosis.
  6. * Current or history of New York Heart Association (NYHA) Stage III or IV heart failure
  7. * Current or history of Interstitial Lung Disease.
  8. * Current or history of glaucoma and/or an intraocular pressure \> 22 mmHg, retinal pigment epithelial detachment, or other primary ocular/retinal diseases.
  9. * Current or history of retinal vein occlusion (RVO).
  10. * Comorbidities that put undue risk of RVO such as uncontrolled hypertension (chronic systolic blood pressures \> 160 mm Hg) and/or uncontrolled diabetes mellitus type II (DMII) (chronic clinical signs/symptoms of hyperglycemia; diabetic participants must have a hemoglobin A1c value \< 9% to be eligible).
  11. * Participants receiving systemic or ocular glucocorticoid therapy equivalent to \> 10 mg of prednisone daily within 14 days prior to the study treatment initiation. Note: Participants with endocrine deficiencies, who receive physiologic, or stress doses of steroids are eligible.
  12. * Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 within 14 days prior to the study treatment initiation. Lists including medications and substances known or with the potential to interact with the CYP3A4 isoenzymes are provided here: http://medicine.iupui.edu/clinpharm/ddis/table.aspx.
  13. * Participants receiving any medications or substances that are strong inhibitors of breast cancer resistance protein (BCRP) within 14 days prior to the study treatment initiation (i.e., curcumin, cyclosporine, darolutamide, eltrombopag, febuxostat, fostamatinib, rolapitant, sofosbuvir and velpatasvir and voxilaprevir, and teriflunomide).
  14. * Positive beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in IOCBP at screening.
  15. * Participant has abnormal QT interval corrected by Fridericia s formula (QTcF \>470 ms, as determined by the mean QTcF values from the ECG assessments at screening (one triplicate).
  16. * Uncontrolled intercurrent illness or factors evaluated by medical history and physical exam that would potentially increase the risk of the participant.

Contacts and Locations

Study Contact

NCI Medical Oncology Referral Office
CONTACT
(240) 760-6050
ncimo_referrals@nih.gov
Elizabeth M Hill, M.D.
CONTACT
(240) 889-5377
elizabeth.hill@nih.gov

Principal Investigator

Elizabeth M Hill, M.D.
PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Elizabeth M Hill, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-06-17
Study Completion Date2033-01-01

Study Record Updates

Study Start Date2025-06-17
Study Completion Date2033-01-01

Terms related to this study

Keywords Provided by Researchers

  • KRAS
  • NRAS

Additional Relevant MeSH Terms

  • Multiple Myeloma
  • Relapsed and/or Refractory Multiple Myeloma (RRMM)