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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-08

Study Completion Date

2027-12-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Selinexor, Carfilzomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT02199665

Refractory Multiple Myeloma

COMPLETED PHASE1

Personalized Selinexor-based Therapy for Relapsed/Refractory Multiple Myeloma

NCT04925193

Multiple Myeloma in Relapse

ACTIVE_NOT_RECRUITING PHASE2

Selinexor, Pomalidomide, and Dexamethasone With or Without Carfilzomib for the Treatment of Patients With Relapsed Refractory Multiple Myeloma, The SCOPE Trial

NCT04764942

Recurrent Multiple Myeloma Refractory Multiple Myeloma

ACTIVE_NOT_RECRUITING PHASE1/PHASE2

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

NCT04661137

Multiple Myeloma

SUSPENDED PHASE2

Selinexor Treatment of Refractory Myeloma

NCT02336815

Multiple Myeloma

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVE:

I. To evaluate the minimal residual disease (MRD) negativity rate, at 10\^-5 level of sensitivity by flow cytometry in bone marrow, with the addition of selinexor to daratumumab, carfilzomib and dexamethasone (SKDd) in patients with high-risk, relapsed or relapsed/refractory multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the overall response rate (partial response \[PR\] or better) of patients receiving SDKd combination for high risk, relapsed or relapsed/refractory multiple myeloma (MM) and assess depth of response (very good partial response \[VGPR\], complete response \[CR\], stringent complete response \[sCR\]).

II. To evaluate the time to response and duration of response in patients receiving SDKd combination for MM.

III. To evaluate the progression free survival and overall survival in patient receiving SDKd.

IV. To evaluate the MRD negativity rates to the level of sensitivity 10\^-6 by flow cytometry in bone marrow.

V. To evaluate the safety profile of the SDKd combination.

CORRELATIVE RESEARCH OBJECTIVES:

I. To explore the impact of baseline immunomodulatory derivative (IMiD)-14 scores gene expression profile (GEP) on progression free survival.

II. Quality of life assessment utilizing Quality of Life Questionnaire (QLQ)-Core (C) 30 and QLQ-Multiple Myeloma (MY) 20 (Cocks et al., 2007; Wisloff et al., 1996).

OUTLINE:

Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 8, and 15 and daratumumab IV as a split dose on cycle 1 days 1 and 2 then on days 8, 15, and 22 of cycle 1, then on 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 orally (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.

After completion of study treatment, patients without disease progression/clinical relapse or have initiated subsequent anti-cancer therapy, are followed up every 3 months until progression/clinical relapse or initiation of subsequent anti-cancer therapy, and then every 6 months for up to 5 years. Patients with disease progression/clinical relapse or have initiated subsequent anti-cancer therapy are followed up every 6 months for up to 5 years.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment (carfilzomib, daratumumab, dexamethasone, selinexor)

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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Given IV

Daratumumab

Intervention Type BIOLOGICAL

Given IV

Dexamethasone

Intervention Type DRUG

Given PO

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Selinexor

Intervention Type DRUG

Given PO

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Carfilzomib

Given IV

Intervention Type DRUG

Daratumumab

Given IV

Intervention Type BIOLOGICAL

Dexamethasone

Given PO

Intervention Type DRUG

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Selinexor

Given PO

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Kyprolis PR-171 Anti-CD38 Monoclonal Antibody Darzalex HuMax-CD38 JNJ-54767414 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 Quality of Life Assessment ATG-010 CRM1 Nuclear Export Inhibitor KPT-330 KPT-330 Selective Inhibitor of Nuclear Export KPT-330 SINE KPT-330 Xpovio

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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
* Early relapse with first-line therapy

* =\< 18 months from cycle 1 day 1 for patients not undergoing autologous stem cell transplant (ASCT)
* =\< 36 months from cycle 1 day 1 for patients undergoing ASCT and post-ASCT maintenance
* Measurable disease
* 1-3 prior lines of therapy
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2 (Form is available on the Academic and Community Cancer Research United \[ACCRU\] website)
* Patients must have evidence of adequate bone marrow reserves, as defined by the following:

* Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 without filgrastim or its equivalent within 1 week of the initiation of treatment or pegfilgrastim or its equivalent within 2 weeks of the initiation of treatment
* Platelet count of \>= 100,000 cells/mm\^3 for patients who have bone marrow plasmacytosis of \< 50%, or \>= 50,000 cells/mm\^3 for patients who have bone marrow plasmacytosis of \> 50%, both without platelet transfusion support within 1 week of the initiation of treatment or the use of TPO mimetics
* NOTE: If your site laboratory reports use different units of measurements than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"
* Total bilirubin =\< 2.0 times the upper limit of the institutional normal values except in subjects with congenital bilirubinemia, such as Gilbert syndrome (in which case a direct bilirubin =\< 1.5 x upper limit of normal \[ULN\] is required)
* Total aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times the upper limit of the institutional normal values
* Patients must have adequate cardiac function defined as left ventricular ejection fraction (LVEF) \>= 45% by echocardiogram, magnetic resonance imaging (MRI) or multigated acquisition (MUGA) scan
* For those with symptomatic pulmonary disease (e.g. chronic obstructive pulmonary disease \[COPD\], asthma) or other signs/symptoms of pulmonary disease, adequate pulmonary function as defined by a forced expiratory volume in one second (FEV1) \>= 50% of predicted and diffusing capacity for carbon monoxide (DLCO)/alveolar volume (VA) \>= 50% of predicted within 28 days prior to day 1 of treatment

* Note: Baseline pulmonary function tests are only required on an as needed basis
* Patients must have evidence of adequate renal function, as defined by the following: creatinine clearance (CrCl) \>= 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula

* Calculated creatinine clearance must be \>= 30 ml/min using the Cockcroft-Gault formula
* Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
* Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective (dual methods of) contraception throughout the study and for 6 months following the last dose of study drug; and male patients must use an effective barrier method of contraception throughout the study and for 3 months following the last dose of study drug if sexually active
* Ability to complete questionnaire(s) by themselves or with assistance
* Provide informed written consent =\< 28 days prior to registration
* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria

* 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)
* Note: Prior to study entry, any EKG abnormality at screening not felt to put the patient at risk must be documented by the investigator as not medically significant
* A diagnosis of human immunodeficiency virus (HIV) does not exclude the patient from participation. However, the viral load must be \< 50 copies/mm\^3 and CD4 count \>= 200 on anti-HIV therapy within 28 days prior to cycle 1, day 1 of treatment
* Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening

* NOTE: Subjects with positive hepatitis C antibody due to prior eradicated disease can be enrolled if a confirmatory negative hepatitis C RNA test is obtained
* Is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (i.e. subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Subjects who are PCR positive will be excluded. Exception: patients with serologic findings suggestive of HBV vaccination
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
* Discontinuation of prior carfilzomib or daratumumab due to treatment toxicity
* Radiation within 14 days prior to day 1 of treatment. Note: palliative radiation therapy (XRT) to \< 5% of the total marrow volume as assessed by the treating investigator is allowed within 14 days
* Major surgery within 4 weeks prior to day 1 of treatment
* Any multiple myeloma therapy within 14 days prior to cycle 1, day 1
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Active central nervous system (CNS) involvement
* Concomitant amyloid light-chain (AL) amyloidosis or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
* Patients cannot have other prior or concomitant malignancies except for:

* Non-melanoma skin cancer
* In situ malignancy
* Low-risk prostate cancer after curative therapy
* Prostate cancer Gleason grade 6 AND with stable prostate specific antigen (PSA) levels off treatment
* Other cancer for which the patient has been treated with curative intent or disease free for \>= 3 years
* Prior exposure to daratumumab within 24 weeks from cycle 1, day 1

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No