A Trial of Selinexor, Ruxolitinib and Methylprednisolone

Recruiting now · Phase 1

Conditions studied: Multiple Myeloma in Relapse, Multiple Myeloma, Refractory

In brief

Selinexor, a first-in-class, oral selective exportin 1 (XPO1) inhibitor, has shown promise in pre-clinical and clinical studies. It functions by inhibiting the nuclear export protein XPO1, resulting in the accumulation of tumor suppressor proteins and inhibition of oncoprotein mRNAs, which is selectively lethal to myeloma cells. Selinexor has demonstrated activity in combination with various drugs, including glucocorticoids and proteasome inhibitors, leading to its FDA approval for the treatment of relapsed or refractory multiple myeloma.

Key facts

Study ID

NCT06225310

Run by

Oncotherapeutics

People needed

30

Starts

2024-08-06

Expected to finish

2027-05-01

Last updated by the study team

2025-01-16

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must meet all the following inclusion criteria to be eligible to enroll in this study:
• Has a diagnosis of MM based on standard criteria as follows:
• Myeloma criteria: Must be At least 1 of 2 1. Clonal bone marrow plasma cells >10% 2. Biopsy-proven bony or extramedullary plasmacytoma
• Active Myeloma criteria: Active Myeloma criteria: Must Meet At Least ONE of the Following:
• Meet at least one of the sub-criteria for #1 Evidence of End Organ Damage (a, b, c, or d), OR Meet sub-criteria #2. 60% or greater bone marrow plasma cells, OR Meet sub-criteria #3 Serum free light chain ratio, OR Meet sub-criteria #4 More than one focal lesion on MRI > 5mm in size.
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically
• Hypercalcemia: serum calcium >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL)
• Renal insufficiency: creatinine clearance <40 mL per minute or serum creatinine >177mol/L (>2mg/dL)
• Anemia: hemoglobin value of >20g/L below the lowest limit of normal, or a hemoglobin value <100g/L
• Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT. If bone marrow has <10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement
• 60% or greater clonal plasma cells on bone marrow examination
• Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100 mg/L (a patient's involved free light chain either kappa or lambda is the one that is above the normal reference range; the uninvolved free light chain is the one that is typically in, or below, the normal range)
• More than one focal lesion on MRI that is at least 5mm or greater in size
• The patient must have met the criteria for Active Myeloma at some stage following the diagnosis of Myeloma. Source documentation for both Myeloma and Active Myeloma will be required.
• Patients with relapsed/refractory multiple myeloma with at least three prior lines of therapy 3. Received an
• Anti-CD38 antibody
• Immunomodulatory agent (IMiD)
• Proteasome inhibitor (PI) 4. Currently has MM with measurable disease, defined as:
• a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL and/or urine monoclonal protein levels of at least 200 mg/24 hours
• for patients without measurable serum and urine M-protein levels, an involved SFLC > 100 mg/L or abnormal SFLC ratio
• for patients with IgD MM, a monoclonal immunoglobulin IgD of at least 5500 mg/L or meet other measurable disease eligibility criteria
• for patients with IgA MM, total IgA of > 700 mg/dL 5. Currently has progressive MM: MM patients that are relapsed or have refractory disease from at least 3 regimens or lines of therapy are eligible for enrollment provided they fulfill the other eligibility criteria:
• patients are considered relapsed, when they progress greater than 60 days from their last dose of treatment
• patients are refractory when they progress while currently receiving the treatment or within 8 weeks of its last dose 6. Adequate hepatic function within 14 days prior to C1D1: Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 × ULN), and Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to < 2 × ULN.
• Adequate renal function within 14 days prior to C1D1 as determined by OR estimated CrCl of > 60 mL/min, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female (87)(Appendix 5).

You may not qualify if…

• Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:
• Patients who had prior exposure to ruxolitinib or selinexor
• Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 3 years prior to randomization. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.
• Have light chain amyloidosis
• Have plasma cell leukemia
• Have history of active tuberculosis
• Have any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, POEMS syndrome [polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes], primary amyloidosis, etc.) that is likely to interfere with study procedures.
• Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
• Received the following prior therapy:
• Chemotherapy within 3 weeks of study drugs
• Corticosteroids (>20 mg/daily prednisone or equivalent) within 3 weeks of study drugs to ensure that steroid dose intensity at the beginning of the treatment is not altered by administration of steroids prior to the study. Consumption of steroids within 3 weeks of the treatment may interfere with efficacy and side effects due to differences of steroid intensity.
• Immunotherapy, immunomodulatory drugs, or proteasome inhibitors within 3 weeks before administration of study drugs
• Extensive radiation therapy within 28 days before study drugs. Receipt of localized radiation therapy does not preclude enrollment.
• Use of any other experimental drug or therapy within 28 days of study drugs
• Strong CYP3A4 inhibitors, strong CYP3A4 inducers and fluconazole doses >200 mg daily within 5 half-lives before study drugs. (For example, clarithromycin has half-life of 4 hours so washout period for clarithromycin is 20 hours.)
• Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
• Known hypersensitivity to compounds of similar chemical or biological composition to ruxolitinib or steroids.
• Concurrent use of other anti-cancer agents or treatments.
• Severe hypercalcemia, i.e., serum calcium ≥ 12 mg/dL (3.0 mmol/L) corrected for albumin
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Pregnant or breastfeeding females.
• Body surface area (BSA) <1.4 m2 at baseline, calculated by the Dubois or Mosteller method.
• Life expectancy of less than 3 months.
• Major surgery within 4 weeks prior to C1D1.
• Active, unstable cardiovascular function, as indicated by the presence of:

Where it is running

• Berenson Cancer Center — West Hollywood, California, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.