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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Age ≥18 years at time of informed consent. 2. 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.
3. 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. 4. 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).
5. 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. 6. ECOG 2 or less. 7. Adequate hepatic function within 28 days prior to C1D1: 1. 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. 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to <2 × ULN. 8. 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).
9. Adequate hematopoietic function within 7 days prior to C1D1: total white blood cell (WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3, hemoglobin ≥8.5 g/dL and platelet count ≥75,000/mm3 (patients for whom <50% of bone marrow nucleated cells are plasma cells) or ≥50,000/mm3 (patients for whom ≥50% of bone marrow nucleated cells are plasma cells). 1. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study. 2. Patients must have:
  • - At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the Screening hemoglobin assessment, and.
  • - At least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment.
However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study. 10. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.

Exclusion Criteria:

  • - Patients meeting any of the following exclusion criteria are not eligible to enroll in this study: 1.
Smoldering MM. 2. 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. 3. Active graft versus host disease after allogeneic stem cell transplant. 4. Life expectancy <3 months. 5. 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. 6. 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. 7. 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. 8. Known intolerance, hypersensitivity, or contraindication to glucocorticoids. 9. Pregnant or breastfeeding females. 10. Body surface area (BSA) <1.4 m2 at baseline, calculated by the Dubois (Dubois 1916) or Mosteller (Mosteller 1987) method. 11. 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. 12. 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). 13. 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. 14. Contraindication to any of the required concomitant drugs or supportive treatments. 15. Patients unwilling or unable to comply with the protocol

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04661137
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Hackensack Meridian Health
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Noa Biran, MD
Principal Investigator Affiliation Hackensack Meridian Health
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Additional Details

This is a Phase 2b, two-arm, open-label, multicenter study of Sd (selinexor 100, 80 or 60 mg) in combination with carfilzomib, or pomalidomide in patients with MM previously treated with carfilzomib or pomalidomide respectively, and refractory to prior treatment. An additional exploratory arm will focus on patients treated with SD in combination with daratumumab. This study will enroll approximately 96 patients overall (43 in each of the arms and 10 additional patients in the exploratory arm. Patients will be assigned to the respective arms based on their previous treatment. Patients who are relapsed or refractory to their current carfilzomib-based regimen will be enrolled on Arm 1 and will receive the following treatment regimen on a 28-day cycle: Carfilzomib 56 mg/m2 on days 1, 8 and 15. They will also receive dexamethasone 40 mg (or 20 mg if patient is ≥ 75 years old) once weekly and Selinexor 80 mg on days 1, 8 and 15. Patients who are relapsed or refractory to their current pomalidomide-based regimen will be enrolled on Arm 2 and will receive the following treatment regimen on a 28-day cycle: Pomalidomide 4 mg po daily for 21 days combined with Dexamethasone 40 mg (or 20 mg if patient is ≥ 75 years old) once weekly and Selinexor 60 mg days 1, 8 and 15. For arms 1 and 2, 13 patients will be accrued in each arm in the first stage. If there are 3 or fewer responses in these 13 patients, the study will be stopped. Otherwise, 30 additional patients will be accrued for a total of 43 (in each arm). Finally, in the exploratory arm, we will enroll up to 10 patients who are relapsed or refractory to their current daratumumab-based regimen. Patients enrolled on the exploratory arm will receive the following treatment regimen on a 28-day cycle: Daratumumab on current schedule (16 mg/kg IV days 1,8,15,22 for cycles 1-2; days 1 and 15 for cycles 3-6; day 1 for cycle 7 and on) combined with Dexamethasone 40 mg once weekly (or 20 mg if patient is ≥ 75 years old) and Selinexor 100 mg once weekly. The Investigator may remove a patient from study treatment using criteria described in Section 10.2. Patients may decide to discontinue study treatment for any reason. Patients who elect to discontinue study treatment should be encouraged to continue in the study so that follow-up information on disease progression, other antineoplastic therapy, symptoms and survival status may be obtained. However, patients may elect to withdraw consent and decline further participation in the trial at any time. The Investigator must determine the primary reason for a patient's discontinuation of study treatment and record this information on the electronic case report form (eCRF). Patients who are prematurely withdrawn from study treatment are not eligible to re-initiate study treatment on this protocol at a later date.

Arms & Interventions

Arms

Experimental: Carfilzomib-containing Regimen

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.

Experimental: Pomalidomide-containing Regimen

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.

Experimental: Exploratory/Daratumumab-containing Regimen

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.

Interventions

Drug: - Selinexor 60 MG

Selinexor 60 mg PO on days 1, 8 and 15

Drug: - Selinexor 80 MG

Selinexor 80 mg PO on days 1, 8 and 15

Drug: - Selinexor 100 MG

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

Drug: - Carfilzomib

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

Drug: - Pomalidomide

4 mg PO daily for 21 days

Drug: - Daratumumab

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

Drug: - Dexamethasone

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Lombardi Comprehensive Cancer Center, Washington, District of Columbia

Status

Recruiting

Address

Lombardi Comprehensive Cancer Center

Washington, District of Columbia, 20007

Site Contact

Melin Vranesic

mv764@georgetown.edu

202-687-0160

John Theurer Cancer Center, Hackensack, New Jersey

Status

Recruiting

Address

John Theurer Cancer Center

Hackensack, New Jersey, 07601

Site Contact

Palka Anand

Palka.Anand@hmhn.org

551-996-3040