Selinexor, Daratumumab, Carfilzomib and Dexamethasone for the Treatment of High-Risk, Recurrent or Refractory Multiple Myeloma

NCT04756401 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: ACCRU-MY-1901NCI-2020-13697P30CA015083
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies the effect of selinexor when combined with carfilzomib, daratumumab, and dexamethasone in treating patients with high-risk multiple myeloma that has come back (recurrent) or has not responded to treatment (refractory) and who have received 1-3 prior lines of therapy. Selinexor may stop the growth of cancer cells by blocking a protein called CRM1 that is needed for cell growth. Carfilzomib is a type of drug called a proteasome inhibitor. A proteasome is a protein found within cells that has the important role of identifying and marking damaged proteins that are needed to be destroyed by the cell for survival. The inhibition of the proteasome allows for damaged protein to accumulate within cells. This accumulation of damaged protein causes the cell to die. Daratumumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving selinexor in combination with carfilzomib, daratumumab, and dexamethasone may work better than carfilzomib, daratumumab, and dexamethasone alone in treating patients with multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Rate of minimal residual disease (MRD) negative status

  MRD negative status at 10\^-5 level of sensitivity by flow cytometry will be considered synonymous with "success", unless specified otherwise. The proportion of success will be estimated by the number of success divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  Up to 5 years post-treatment

Secondary Outcomes (7)

• Overall response rate (ORR)

  Up to 5 years post-treatment

• Time to response

  Time between registration and earliest date of documentation of response using International Myeloma Working Group criteria, assessed up to 5 years

• Duration of response

  Time between first documentation of response to the earliest date of progression or death, assessed up to 5 years

• Progression-free survival

  Time between registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years

• Overall survival (OS)

  Time between registration to death due to any cause, assessed up to 5 years

Other Outcomes (3)

• Effect of Immunomodulatory imide drug-14 scores gene expression profile (GEP) on Progression-Free Survival

  Baseline up to progression-free survival, assessed up to 5 years

• Change in EORTC QLQ-C30 scores from baseline to end of treatment

  Baseline up to progression, withdrawal, or end of treatment, assessed up to 5 years

• Change in EORTC QLQ-MY20 scores from baseline to end of treatment

  Baseline up to progression, withdrawal, or end of treatment, assessed up to 5 years

Study Arms (1)

Treatment (carfilzomib, daratumumab, dexamethasone, selinexor)

EXPERIMENTAL

Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15 and daratumumab IV on days 1 and 2 of cycle 1 then days 8, 15, and 22 of cycle 1, then, days 1, 8, 15, and 22 of cycle 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Patients also receive dexamethasone PO on days 1, 8 15, and 22, and selinexor PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Carfilzomib; Biological: Daratumumab; Drug: Dexamethasone; Other: Quality-of-Life Assessment; Drug: Selinexor

Interventions

Carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Treatment (carfilzomib, daratumumab, dexamethasone, selinexor)

Daratumumab BIOLOGICAL

Given IV

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Treatment (carfilzomib, daratumumab, dexamethasone, selinexor)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (carfilzomib, daratumumab, dexamethasone, selinexor)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (carfilzomib, daratumumab, dexamethasone, selinexor)

Selinexor DRUG

Given PO

Also known as: ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330, Xpovio

Treatment (carfilzomib, daratumumab, dexamethasone, selinexor)

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
• Patients must have a documented history of relapsed or relapsed/refractory MM as defined by International Myeloma Working Group (IMWG) criteria (Rajkumar et al., 2014)
• Patients must be selinexor and carfilzomib sensitive
• Prior daratumumab exposure is allowed, provided that it has been 6 months or more from the time of cycle 1 day 1 (C1D1) of protocol therapy
• High risk disease defined as 1 or more of the following:
• High risk cytogenetics (any of the following)
• t(4;14), t(14;16), t(14;20)
• del(17p)
• del(1p)
• Gain 1q (\>= 3 copies)
• Lactate dehydrogenase (LDH) \> upper limit of normal at relapse
• International Staging System (ISS) stage 3 disease at relapse
• Extramedullary disease at diagnosis or relapse
• \>= 5% circulating plasma cells at diagnosis or relapse
• High risk by gene expression profiling, if known, at diagnosis or relapse

You may not qualify if:

• Prior treatment with daratumumab within 6 months from cycle 1 day1
• Patient with carfilzomib-refractory disease defined as disease progression on or within 60 days of last carfilzomib dose
• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Uncontrolled hypertension, defined as a systolic blood pressure of \>= 160 mmHg or a diastolic blood pressure of \>= 90 mmHg
• Significant cardiac disease, including any of the following:
• \>= class 3 New York Heart Association (NYHA) congestive heart failure
• Electrocardiogram (EKG) evidence of acute ischemia
• Unstable angina
• Myocardial infarction within 6 months prior to day 1 of treatment
• Clinically significant arrhythmias or conduction block (premature atrial contractions \[PACs\], premature ventricular contractions \[PVCs\], rate controlled atrial fibrillation, sinus arrhythmia, asymptomatic sinus bradycardia or sinus tachycardia and 1st degree heart block are not considered clinically significant)
• \>= grade 2 QT interval by Fridericia (QTcF) prolongation (i.e. \> 480 ms)

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

UNC Lineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; daratumumab; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; selinexor

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

• Shebli Atrash

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: February 16, 2021
• Study Start: December 8, 2022
• Primary Completion: September 30, 2024
• Study Completion (Estimated): December 30, 2027
• Last Updated: September 26, 2024

Record last verified: 2024-09

Locations

US (4)