A Trial of Selinexor, Ruxolitinib and Methylprednisolone

NCT06225310 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: KPT-IST-391
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma, Refractory

Keywords

Multiple Myeloma; Multiple Myeloma, Refractory; Multiple Myeloma in Relapse

Outcome Measures

Primary Outcomes (2)

• 1. Maximum Tolerated Dose (MTD):

  ● A standard 3 + 3 dose escalation schedule will be used for all escalations

  30 months

• 2. Recommended phase 2 dose (RP2D)

  Primary objective of a phase 1 study is to define a safe and tolerable dose to use in further studies designed to determine efficacy, the Recommended Phase 2 Dose (RP2D)

  30 months

Secondary Outcomes (3)

• 1. Overall Response Rate ([ORR]=CR+VGPR+PR)

  30 months

• 2. Clinical Benefit Rate ([CBR]=CR+VGPR+PR+MR)

  30 months

• 3. To determine disease parameters for study treatment:

  30 months

Other Outcomes (1)

• Background and rationale for assessment of serum B cell maturation antigen levels (sBCMA)

  30 months

Study Arms (1)

Experimental: Selinexor/Ruxolitinib/Steroids

OTHER

The regimen will follow a 3+3 dose escalation schedule starting at dose level 0. Subjects enrolled at dose level 0 will receive 1) selinexor (once weekly) starting at 40 mg, 2) ruxolitinib (twice a day (BID) on days 1-28) starting at 10 mg, and 3) oral methylprednisolone (every other day (QOD)) a set dose at 40 mg. Subjects at dose level 1 will receive 1) selinexor (once weekly) 60 mg, 2) ruxolitinib (BID) on days 1-28 10 mg, and 3) methylprednisolone (QOD) 40 mg. Subjects at dose level 2 will receive 1) selinexor (once weekly) 60 mg, 2) ruxolitinib (BID) on days 1-28 15 mg, and 3) oral methylprednisolone (QOD) 40 mg.

Drug: Selinexor; Drug: Ruxolitinib; Drug: Methylprednisolone

Interventions

Selinexor DRUG

Selinexor (KPT-330) is a first-in-class, oral selective exportin 1 (XPO1) inhibitor (1,2). Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in t

Also known as: XPOVIO

Experimental: Selinexor/Ruxolitinib/Steroids

Ruxolitinib DRUG

elective inhibitor of Janus kinase (JAK)

Also known as: Jakafi

Experimental: Selinexor/Ruxolitinib/Steroids

Methylprednisolone DRUG

Glucocorticoid, steroid

Also known as: Medrol

Experimental: Selinexor/Ruxolitinib/Steroids

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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
• % 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oncotherapeutics: lead

Study Sites (1)

Berenson Cancer Center

West Hollywood, California, 90069, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; ruxolitinib; Methylprednisolone

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

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• James Berenson, MD

  Oncotherapeutics

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard Bailey

CONTACT

310-464-2190; rbailey@oncotherapeutics.com

Yohana Sebhat

CONTACT

310-810-3158; ysebhat@oncotherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2023
• First Posted: January 25, 2024
• Study Start: August 6, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: January 16, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)