Study of Selinexor Plus DRd for Newly Diagnosed Multiple Myeloma

NCT04782687 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 20285IST-337
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 10

Brief Summary

This is a single-arm, phase II, open-label trial to investigate the effects of selinexor (S) in combination with daratumumab, lenalidomide, and dexamethasone (DRd) for first-line treatment of multiple myeloma (MM). FDA has approved selinexor plus dexamethasone in multiple myeloma after four prior therapies, and DRd is also already approved by the FDA for multiple myeloma. This study will use all four (S-DRd) together to treat MM as an initial treatment.

Conditions

Multiple Myeloma; Myeloma Multiple; Kahler Disease; Myeloma, Plasma Cell; Myeloma-Multiple; Myelomatosis; Plasma Cell Myeloma

Keywords

myeloma; cancer; newly diagnosed multiple myeloma

Outcome Measures

Primary Outcomes (3)

• Complete Response Rate (CR)

  percentage of patients who had complete response. Complete response is when patients achieve a negative immunofixation on the serum and urine and who also have an appearance of a soft tissue plasmacytomas and achieve less than or equal to 5 percent (%) plasma cells in the bone marrow.

  6 months

• Stringent Complete Response Rate (sCR)

  percentage of patients who had stringent complete response. Patients with a stringent complete response in addition to the criteria that is required to have a complete response are required to have a normal free light chain ratio in the serum and absence of clonal cells in the bone marrow determined by either immunofluorescence or immunohistochemistry.

  6 months

• Safety of Selinexor plus DRd

  frequency (incidence rate) of adverse effects

  3 years

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  3 years

• Time to Next Treatment (TTNT)

  3 years

• Duration of Response

  3 years

• Progression-Free Survival (PFS)

  3 years

• Overall Survival (OS)

  3 years

Study Arms (1)

Selinexor plus DRd

EXPERIMENTAL

1. Lenalidomide 15 mg orally on Days 1-21 of each 28-day cycle 2. Dexamethasone 40 mg on Days 1, 8, 15, 22 of each cycle. However, those \>75 years old may be administered a weekly dose of 20 mg dexamethasone. 3. Daratumumab 1800 mg subcutaneous injection once weekly in Cycles 1 and 2, every 2 weeks in cycles 3 to 6, and every 4 weeks thereafter. 4. Selinexor 60 mg on Days 1, 8, 15, of cycles 1-3, with a planned dose-reduction to 40 mg on Days 1, 8, 15 for cycles beyond 3. If patient was previously dose reduced prior to cycle 4, then at cycle 4 planned dose reduction, you will again decrease dose by 1 level.

Drug: Selinexor; Drug: Dexamethasone Oral; Drug: Daratumumab; Drug: Lenalidomide

Interventions

Selinexor DRUG

oral drug that comes in 20 mg tablets

Also known as: Xpovio

Selinexor plus DRd

Dexamethasone Oral DRUG

Dexamethasone 40 mg on Days 1, 8, 15, 22 of each cycle. However, those \>75 years old may be administered a weekly dose of 20 mg dexamethasone.

Selinexor plus DRd

Daratumumab DRUG

Patients will receive daratumumab subcutaneously (SC, or under the skin) as an injection. The recommended dosage of the SC formulation is 1,800 mg daratumumab and 30,000 units hyaluronidase administered SC into the abdomen over approximately 3 to 5 minutes according to recommended schedule. Daratumumab 1800 mg subcutaneously once weekly in Cycles 1 and 2, every 2 weeks in cycles 3 to 6, and every 4 weeks thereafter.

Also known as: Darzalex

Selinexor plus DRd

Lenalidomide DRUG

Patients will receive a 21-day supply of lenalidomide (15 mg) as oral capsules, as appropriate, for each 28-day treatment cycle

Also known as: Revlimid

Selinexor plus DRd

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age.
• Have documented multiple myeloma as defined by the International Myeloma Working Group (IMWG) 2015 criteria below:
• Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma. \* In addition, the patient must meet one of the criteria in either 2a or 2b.
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically at least one of the following:
• i. Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL)
• ii. Renal insufficiency: creatinine clearance 20-40 mL per min or serum creatinine \>177 μmol/L (\>2 mg/dL)
• iii. Anemia: hemoglobin value of \> 2 g/dL below the lower limit of normal, or a hemoglobin value \<10 g/dL\*
• iv. Bone lesions: one or more osteolytic lesions on skeletal radiography, or CT (computed tomography) \*\*.
• Any one or more of the following:
• i. Clonal bone marrow plasma cell percentage\* ≥60%
• ii. Involved: uninvolved serum free light chains (FLC) ratio\*\*\* \>100
• iii. \>1 focal lesions on MRI (magnetic resonance imaging) studies; Each focal lesion must be 5 mm or more in size.
• Clonality should be established by showing κ/λ-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used.
• If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement.
• These values are based on the serum Freelite assay. The involved FLC must be ≥100 mg/L.

You may not qualify if:

• Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma.
• Is known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C.
• Patients who completed treatment for hepatitis C and have no detectable circulating hepatitis C virus (HCV) by hepatitis C RNA polymerase chain reaction (PCR) for at least 6 months prior to screening, may participate in the study. Such patients will be required to undergo regular assessment for HCV reactivation during their participation in the study. Patients who test positive for HCV at any time during these assessments will be withdrawn from the study.
• Has any concurrent medical condition or disease (e.g., active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
• Has clinically significant cardiac disease, including:
• Myocardial infarction (MI) within 6 months before first day of first cycle (C1D1), or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV)
• Uncontrolled cardiac arrhythmia (NCI-CTCAE Version 5.0 Grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities
• Screening 12-lead ECG shows a baseline QT interval (QTc) \>470 msec
• Has any of the following laboratory test results during the screening phase:
• Absolute neutrophil count ≤1.0 × 109 /L; (granulocyte colony stimulating factor use is permitted)
• Hemoglobin level ≤7.5 g/dL (≤5 mmol/L); blood transfusions to maintain hemoglobin \>7.5 are acceptable
• Platelet count \<75 × 109 /L for patients in whom \<50% of bone marrow nucleated cells are plasma cells; otherwise platelet count \<50 × 109 /L; no platelet transfusions in the past 7 days are allowed
• Alanine aminotransferase (ALT) level ≥2.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) level ≥2.5 × ULN
• Total bilirubin level ≥1.5 × ULN, (except for Gilbert Syndrome: direct bilirubin 2 × ULN)

Sponsors & Collaborators

• US Oncology Research: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (10)

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85711, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Maryland Oncology Hematology, P.A.

Columbia, Maryland, 21044, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12206, United States

Location

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401, United States

Location

Texas Oncology, P.A.

Austin, Texas, 78705, United States

Location

Texas Oncology, P.A.

Fort Worth, Texas, 76104, United States

Location

Texas Oncology, P.A.

San Antonio, Texas, 78240, United States

Location

Texas Oncology, P.A.

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists, PC

Gainesville, Virginia, 20155, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms

Interventions

selinexor; Dexamethasone; daratumumab; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; 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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Robert M Rifkin, MD, FACP

  US Oncology Research/McKesson Specialty Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-arm, phase II, open-label, non-blinded, trial to investigate the effects of S-DRd for first line treatment of multiple myeloma in patients who are ineligible for stem cell transplant.

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 4, 2021
• Study Start: September 10, 2021
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: January 16, 2025

Record last verified: 2025-01

Locations

US (10)