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

Primary Purpose

Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carfilzomib
Daratumumab
Dexamethasone
Quality-of-Life Assessment
Selinexor
Sponsored by
Academic and Community Cancer Research United
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Plasma Cell Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Iowa-Wide Oncology Research Coalition NCORP
  • Mayo Clinic in Rochester
  • Coborn Cancer Center at Saint Cloud Hospital
  • Hackensack University Medical Center
  • State University of New York Upstate Medical UniversityRecruiting
  • Carolinas Medical Center/Levine Cancer InstituteRecruiting
  • Spartanburg Regional Medical Center
  • Guthrie Medical Group PC-Robert Packer Hospital
  • Marshfield Clinic Cancer Center at Sacred Heart
  • Aurora Cancer Care-Milwaukee West

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (carfilzomib, daratumumab, dexamethasone, selinexor)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall response rate (ORR)
Will be estimated by the total number of patients who achieve a confirmed response at any time divided by the total number of evaluable patients. A confirmed response is defined as a partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) noted as the objective status on two consecutive evaluations at least two weeks apart. Exact binomial 95% confidence intervals for the true overall response rate will be calculated. The depth of response (PR versus VGPR versus CR versus sCR) will also be summarized.
Time to response
Time to response (TTR) is defined as time from the date of registration to the date of confirmed response using IMWG criteria. TTR will be summarized descriptively (median, range).
Duration of response
Duration of response (DOR) is defined as time from date at which the patient's confirmed objective status is noted to the earliest date of progression or death. The DOR will be estimated using the method of Kaplan-Meier.
Progression-free survival
The progression free survival (PFS) is defined as the time from registration to the earliest date of documentation of disease progression or death due to any cause. The distribution of PFS will be estimated using method of Kaplan-Meier.
Overall survival (OS)
The overall survival (OS) is defined as the time from registration to death due to any cause. The distribution of OS will be estimated using method of Kaplan-Meier.
MRD negativity rate at 10^-6 of sensitivity
Will be assessed in the bone marrow by flow cytometry estimated as the number of patients who have achieved MRD negative result at 10^-6 level of sensitivity at any time divided by the total number of evaluable patients. Exact 95% binomial confidence intervals for the true rate of MRD negative response will also be calculated.
Incidence of adverse events
Will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse events to the study treatment will be taken into consideration.

Full Information

First Posted
January 4, 2021
Last Updated
October 11, 2023
Sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04756401
Brief Title
Selinexor, Daratumumab, Carfilzomib and Dexamethasone for the Treatment of High-Risk, Recurrent or Refractory Multiple Myeloma
Official Title
Open Label, Phase 2, Single-Arm Study of Selinexor, Daratumumab, Carfilzomib and Dexamethasone for High-Risk, Relapsed and Relapsed/Refractory Multiple Myeloma Patients Who Have Received 1 - 3 Prior Lines of Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 8, 2022 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
December 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Plasma Cell Myeloma, Refractory Plasma Cell Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (carfilzomib, daratumumab, dexamethasone, selinexor)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Kyprolis, PR-171
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
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
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Drug
Intervention Name(s)
Selinexor
Other Intervention Name(s)
ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330, SINE KPT-330, Xpovio
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Rate of minimal residual disease (MRD) negative status
Description
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.
Time Frame
Up to 5 years post-treatment
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
Will be estimated by the total number of patients who achieve a confirmed response at any time divided by the total number of evaluable patients. A confirmed response is defined as a partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) noted as the objective status on two consecutive evaluations at least two weeks apart. Exact binomial 95% confidence intervals for the true overall response rate will be calculated. The depth of response (PR versus VGPR versus CR versus sCR) will also be summarized.
Time Frame
Up to 5 years post-treatment
Title
Time to response
Description
Time to response (TTR) is defined as time from the date of registration to the date of confirmed response using IMWG criteria. TTR will be summarized descriptively (median, range).
Time Frame
Time between registration and earliest date of documentation of response using International Myeloma Working Group criteria, assessed up to 5 years
Title
Duration of response
Description
Duration of response (DOR) is defined as time from date at which the patient's confirmed objective status is noted to the earliest date of progression or death. The DOR will be estimated using the method of Kaplan-Meier.
Time Frame
Time between first documentation of response to the earliest date of progression or death, assessed up to 5 years
Title
Progression-free survival
Description
The progression free survival (PFS) is defined as the time from registration to the earliest date of documentation of disease progression or death due to any cause. The distribution of PFS will be estimated using method of Kaplan-Meier.
Time Frame
Time between registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years
Title
Overall survival (OS)
Description
The overall survival (OS) is defined as the time from registration to death due to any cause. The distribution of OS will be estimated using method of Kaplan-Meier.
Time Frame
Time between registration to death due to any cause, assessed up to 5 years
Title
MRD negativity rate at 10^-6 of sensitivity
Description
Will be assessed in the bone marrow by flow cytometry estimated as the number of patients who have achieved MRD negative result at 10^-6 level of sensitivity at any time divided by the total number of evaluable patients. Exact 95% binomial confidence intervals for the true rate of MRD negative response will also be calculated.
Time Frame
Up to 5 years post-treatment
Title
Incidence of adverse events
Description
Will be assessed per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse events to the study treatment will be taken into consideration.
Time Frame
Up to 30 days after the last dose of study drug or until the start of subsequent antineoplastic therapy, whichever occurs first
Other Pre-specified Outcome Measures:
Title
Effect of Immunomodulatory imide drug-14 scores gene expression profile (GEP) on Progression-Free Survival
Description
The progression free survival (PFS) is defined as the time from registration to the earliest date of documentation of disease progression or death due to any cause. Patients will be categorized by their GEP and progression-free survival estimates will be compared across GEP scores.
Time Frame
Baseline up to progression-free survival, assessed up to 5 years
Title
Change in EORTC QLQ-C30 scores from baseline to end of treatment
Description
QOL will be measured using the EORTC QLQ-C30, a patient-reported questionnaire about patient ability to function, symptoms related to the cancer and its treatment, overall health and quality of life, and perceived financial impact of the cancer and its treatment. Changes in raw score from baseline to end of treatment will be assessed, in each of the physical and mental health domains. The Wilcoxon signed-rank test will be utilized to assess changes in raw scores. Mean change, along with standard deviation will be reported.
Time Frame
Baseline up to progression, withdrawal, or end of treatment, assessed up to 5 years
Title
Change in EORTC QLQ-MY20 scores from baseline to end of treatment
Description
QOL will be measured using the QLQ-MY20, a patient-reported questionnaire about patient ability to function, symptoms related to the cancer and its treatment, overall health and quality of life, and perceived financial impact of the cancer and its treatment. Changes in raw score from baseline to end of treatment will be assessed, in each of the physical and mental health domains. The Wilcoxon signed-rank test will be utilized to assess changes in raw scores. Mean change, along with standard deviation will be reported.
Time Frame
Baseline up to progression, withdrawal, or end of treatment, assessed up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shebli Atrash
Organizational Affiliation
Academic and Community Cancer Research United
Official's Role
Principal Investigator
Facility Information:
Facility Name
Iowa-Wide Oncology Research Coalition NCORP
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Individual Site Status
Withdrawn
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Withdrawn
Facility Name
Coborn Cancer Center at Saint Cloud Hospital
City
Saint Cloud
State/Province
Minnesota
ZIP/Postal Code
56303
Country
United States
Individual Site Status
Withdrawn
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Noa Biran
Phone
201-996-2879
Email
noa.biran@hackensackmeridian.org
First Name & Middle Initial & Last Name & Degree
Noa Biran
Facility Name
State University of New York Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kelsey Christo
Phone
315-464-4501
Email
christok@upstate.edu
First Name & Middle Initial & Last Name & Degree
Krishna Ghimire, MD
Facility Name
Carolinas Medical Center/Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shebli Atrash
Phone
704-774-9322
Email
Shebli.Atrash@atriumhealth.org
First Name & Middle Initial & Last Name & Degree
Shebli Atrash
Facility Name
Spartanburg Regional Medical Center
City
Forest City
State/Province
North Carolina
ZIP/Postal Code
28043
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ACCRU Operation
Phone
507-538-7448
Email
ACCRU@mayo.edu
First Name & Middle Initial & Last Name & Degree
Asim R. Pati
Facility Name
Guthrie Medical Group PC-Robert Packer Hospital
City
Sayre
State/Province
Pennsylvania
ZIP/Postal Code
18840
Country
United States
Individual Site Status
Withdrawn
Facility Name
Marshfield Clinic Cancer Center at Sacred Heart
City
Eau Claire
State/Province
Wisconsin
ZIP/Postal Code
54701
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ACCRU Operation
Phone
507-538-7448
Email
ACCRU@mayo.edu
First Name & Middle Initial & Last Name & Degree
Adedayo A. Onitilo
Facility Name
Aurora Cancer Care-Milwaukee West
City
Wauwatosa
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Withdrawn

12. IPD Sharing Statement

Learn more about this trial

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

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