A Study of Selinexor, in Combination With Carfilzomib, Daratumumab or Pomalidomide in Patients With Multiple Myeloma

NCT04661137 | Suspended Phase 2 DMC FDA Drug

• 2 other identifiers: Pro2020-0369IST-318
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 2

Brief Summary

This is a prospective, 2-arm (with an additional exploratory arm), open-label, multicenter study looking at the response rate of patients receiving selinexor (KPT-330), in combination with carfilzomib, daratumumab or pomalidomide. Multiple Myeloma patients with documented disease progression or refractory disease while on current treatment with any carfilzomib-containing regimen (arm 1), any pomalidomide-containing regimen (arm 2) or any daratumumab-containing regimen (exploratory arm) will be included in the study. Patients will be assigned to the respective groups according to their current treatment. If a subject has received more than one of the above therapies, then assignment will be made at their physician's discretion (e.g treatment decision can be made based upon patient and physician preferred tolerance.). Patients will receive treatment until progressive disease (PD), death, toxicity that cannot be managed by standard of care, or withdrawal, whichever occurs first.

Conditions

Multiple Myeloma

Keywords

Selinexor; KPT-330

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) of patients receiving selinexor with carfilzomib and dexamethasone (Arm 1)

  ORR will include patients who experience partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), based on International Myeloma Working Group (IMWG) response criteria (Kumar 2016)

  30 Months

• Overall Response Rate (ORR) of patients receiving selinexor with pomalidomide and dexamethasone (Arm 2)

  ORR will include patients who experience partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), based on International Myeloma Working Group (IMWG) response criteria (Kumar 2016)

  30 Months

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  30 Months

• Overall Survival (OS)

  30 Months

• MRD Negativity

  30 Months

• Incidence of Adverse Events [Safety and Tolerability] using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v 4.03.

  30 Months

• Time To Next Treatment (TTNT)

  30 Months

Other Outcomes (16)

• Overall Response Rate (ORR) of patients receiving selinexor with daratumumab and dexamethasone

  30 Months

• Gut Microbiome analysis

  30 Months

• Immune cell subset analyses

  30 Months

Study Arms (3)

Carfilzomib-containing Regimen

EXPERIMENTAL

Carfilzomib 56 mg/m2 on days 1, 8 and 15. Dexamethasone 20 mg if ≥ 75 years old and 40 mg if \< 75 years old on days 1, 8, 15 and 22. Selinexor 80 mg on days 1, 8 and 15.

Drug: Selinexor 80 MG; Drug: Carfilzomib; Drug: Dexamethasone

Pomalidomide-containing Regimen

EXPERIMENTAL

Pomalidomide 4 mg po daily for 21 days. Dexamethasone 20 mg if ≥ 75 years old and 40 mg if \< 75 years old on days 1, 8, 15 and 22. Selinexor 60 mg on days 1, 8 and 15.

Drug: Selinexor 60 MG; Drug: Pomalidomide; Drug: Dexamethasone

Exploratory/Daratumumab-containing Regimen

EXPERIMENTAL

Daratumumab on current schedule (16 mg/kg IV days 1, 8, 15 and 22 for cycles 1-2; days 1 and 15 for cycles 3-6; day 1 for cycle 7 and on). Dexamethasone 20 mg if ≥ 75 years old and 40 mg if \< 75 years old on days 1, 8, 15 and 22. Selinexor 100 mg on days 1, 8, 15 and 22.

Drug: Selinexor 100 MG; Drug: Daratumumab; Drug: Dexamethasone

Interventions

Selinexor 60 MG DRUG

Selinexor 60 mg PO on days 1, 8 and 15

Also known as: KPT-330

Pomalidomide-containing Regimen

Selinexor 80 MG DRUG

Selinexor 80 mg PO on days 1, 8 and 15

Also known as: KPT-330

Carfilzomib-containing Regimen

Selinexor 100 MG DRUG

Selinexor 100 mg PO on days 1, 8, 15 and 22

Also known as: KPT-330

Exploratory/Daratumumab-containing Regimen

Carfilzomib DRUG

56 mg/m2 IV on days 1, 8 and 15

Also known as: Kyprolis

Carfilzomib-containing Regimen

Pomalidomide DRUG

4 mg PO daily for 21 days

Also known as: Pomalyst

Pomalidomide-containing Regimen

Daratumumab DRUG

16 mg/kg IV days 1, 8, 15 and 22 for cycles 1-2; days 1 and 15 for cycles 3-6; day 1 for cycle 7 and on

Also known as: Darzalex

Exploratory/Daratumumab-containing Regimen

Dexamethasone DRUG

20 mg if ≥ 75 years old and 40 mg if \< 75 years old on days 1, 8, 15 and 22

Also known as: Dextenza, Ozurdex, Neofordex, others

Carfilzomib-containing Regimen; Exploratory/Daratumumab-containing Regimen; Pomalidomide-containing Regimen

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years at time of informed consent.
• Histologically confirmed MM and evidence of disease progression while on one of the below MM regimens:
• Arm 1: Refractory to or disease progression while on a carfilzomib-containing regimen
• Arm 2: Refractory to or disease progression while on a pomalidomide-containing regimen
• Exploratory Arm: Refractory to or disease progression while on a daratumumab-containing regimen
• Measurable disease as defined: Serum M-protein ≥ 0.5 g/dL; urine M-protein excretion at least 200 mg/24h; serum FLC ≥ 100 mg/L, provided that FLC is abnormal; if serum protein electrophoresis is felt to be unreliable for routine M-protein measurement (i.e. IgA MM) then quantitative Ig levels by nephelometry or turbidometry are acceptable; for non-secretory disease, bone marrow plasma cells ≥ 20% or a biopsy-proven target lesion by PET/CT or MRI is acceptable
• Documented evidence of disease progression (by IMWG criteria) or refractory disease on the current treatment as defined as:
• Achieving SD or less for ≥ 1 cycle during treatment with regimens stated in #2 (i.e. relapsed) OR
• \<25% response (i.e. never achieved MR) or PD during or within 60 days from the end-of most recent MM regimen as listed in #2 (i.e. refractory).
• Any non-hematological toxicities (except for peripheral neuropathy) that patients experienced from treatments in previous regimens have resolved to Grade 2 or less by Cycle 1 Day 1.
• ECOG 2 or less
• Adequate hepatic function within 28 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 28 days prior to C1D1 as determined by estimated creatinine clearance of ≥ 30 mL/min, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female (Cockcroft 1976).

You may not qualify if:

• Smoldering MM
• Radiation therapy, chemotherapy or immunotherapy other than above stated regimens in #2 ≤2 weeks prior to C1D1. Patients on long-term glucocorticosteroids during screening do not require a washout period. Prior RT is permitted for treatment of fractures or to prevent fractures as well as for pain management.
• Active graft versus host disease after allogeneic stem cell transplant.
• Life expectancy \<3 months.
• Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen.
• Has any concurrent medical condition or disease (eg, uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, 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.
• Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
• Pregnant or breastfeeding females.
• Body surface area (BSA) \<1.4 m2 at baseline, calculated by the Dubois (Dubois 1916) or Mosteller (Mosteller 1987) method.
• Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
• Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (CPGO) (NCCN CPGO) for antiemesis and anorexia/cachexia (palliative care).
• Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
• Contraindication to any of the required concomitant drugs or supportive treatments.
• Patients unwilling or unable to comply with the protocol

Sponsors & Collaborators

• Hackensack Meridian Health: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (2)

Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (12)

• Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.

  PMID: 1244564 BACKGROUND

• Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition. 1989 Sep-Oct;5(5):303-11; discussion 312-3. No abstract available.

  PMID: 2520314 BACKGROUND

• Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987 Oct 22;317(17):1098. doi: 10.1056/NEJM198710223171717. No abstract available.

  PMID: 3657876 BACKGROUND

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

  PMID: 7165009 BACKGROUND

• Fridericia L. Die Systolendauer im elektrokardiogramm bei normalen menschen und bei herzkranken. [The duration of systole in the electrocardiogram of normal subjects and of patients with heart disease.]. Acta Medica Scandinavica. 1920;53:469-86.

  BACKGROUND

• Bahlis N, Chen C, Sebag M et al. A Phase 1B/2 Study of Selinexor in combination with backbone therapies for treatment of relapsed/refractory multiple myeloma. EHA Learning Center. Abstract P277. June 10, 2016.

  BACKGROUND

• Jakubowiak A, Jasielec J, Rosenbaum CA et al. Final Results of Phase 1 MMRC Trial of Selinexor, Carfilzomib, and Dexamethasone in Relapsed/Refractory MM. Blood 2016. 128;973.

  BACKGROUND

• Chari A, et al. Results of the Pivotal STORM Study (Part 2) in Penta-Refractory Multiple Myeloma (MM): Deep and Durable Responses with Oral Selinexor Plus low dose Dexamethasone in Patients with Penta-Refractory MM. Blood. 2018. ASH Abstract 598.

  BACKGROUND

• Gasparetto C, et al. Deep and Durable Respones with Selinexor, Daratumumab and Dexamethasone (SDd) in Patients with MM Previously Exposed to Proteasome Inhibitors and Immunomodulatory Drugs: Results of the Phase 1B Study of SDd. Blood 2018. ASH Abstract 599.

  BACKGROUND

• Gasparetteo C, Lipe B, Tuchman S, et al. Once weekly selinexor, carfilzomib, and dexamethasone (SKd) in patients with relapsed/refractory multiple myeloma (MM). Poster presented at the 2020 American Society of Clinical Oncology Virtual Annual Meeting. J Clin Oncol 38:2020 (suppl; abstr 8530)

  BACKGROUND

• Chen CI, Bahlis N, Gasparetto C, et al. Selinexor, pomalidomide, and dexamethasone (SPd) in patients with relapsed or refractory multiple myeloma. Presented at: American Society of Hematology Annual Meeting; Orlando, Florida. December 6-10, 2019.

  BACKGROUND

• Gasparetto C, Lentzsch S, Schiller GJ et al). Selinexor, daratumumab and dexamethasone in patients with relapsed/refractory multiple myeloma (MM). Poster presented at the 2020 American Society of Oncology Virtual Annual Meeting. J Clin Oncol 38: 2020 (Suppl abstr 8510)

  BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

selinexor; carfilzomib; pomalidomide; daratumumab; Dexamethasone; Calcium Dobesilate

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Noa Biran, MD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 10, 2020
• Study Start: March 16, 2021
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)