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New treatment option for Multiple Myeloma
Official title Selinexor and Backbone Treatments of Multiple Myeloma Patients
ClinicalTrials.gov ID: NCT02343042
What this study is testing
What is Selinexor?
Selinexor is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for multiple myeloma.
Also referred to as KPT-330, XPOVIO®.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This study will independently assess the efficacy and safety of 11 combination therapies in 12 arms, in dose-escalation/-evaluation and expansion phases, for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma (NDMM). The combinations to be evaluated are: Arm 1: Selinexor + dexamethasone + pomalidomide (SPd); enrollment complete Arm 2: Selinexor + dexamethasone + bortezomib (SVd); enrollment complete Arm 3: Selinexor + dexamethasone + lenalidomide (SRd) in RRMM; enrollment complete Arm 4: Selinexor + dexamethasone + pomalidomide + bortezomib (SPVd); enrollment complete Arm 5: Selinexor + dexamethasone + daratumumab (SDd); enrollment complete Arm 6: Selinexor + dexamethasone + carfilzomib (SKd); enrollment complete Arm 7: Selinexor + dexamethasone + lenalidomide (SRd) in NDMM; enrollment complete Arm 8: Selinexor + dexamethasone + ixazomib (SNd); enrollment complete Arm 9: Selinexor + dexamethasone + pomalidomide + elotuzumab (SPEd); enrollment complete Arm 10: Selinexor + dexamethasone + belantamab mafodotin (SBd); enrollment complete Arm 11: Selinexor + dexamethasone + pomalidomide + daratumumab (SDPd); enrollment complete Arm 12: Selinexor + dexamethasone + mezigdomide (SMd); actively recruiting Selinexor pharmacokinetics: PK Run-in (Days 1-14): Starting in protocol version 8.0, patients enrolled to any arm in the Dose Escalation Phase (i.e., Arm 4 [SPVd], Arm 6 [SKd], Arm 8 [SNd], Arm 9 [SPEd], Arm 10 [SBd], and Arm 11 [SDPd]) will also first be enrolled to a pharmacokinetics (PK) Run-in period until 9 patients have been enrolled to this period to evaluate the PK of selinexor before and after co-administration with a strong CYP3A4 inhibitor.
- Phase 2: a mid-size study of how well it works
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Written informed consent signed in accordance with federal, local, and institutional guidelines.
- Age greater than or equal to (≥) 18 years at the time of informed consent.
- Histologically confirmed diagnosis with measurable disease for relapsed/refractory myeloma.
- Symptomatic MM, based on IMWG guidelines.
- Patients must have measurable disease as defined by at least one of the following:
You likely can't join if
- Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:
- Smoldering MM.
- MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead.
- Documented active systemic amyloid light chain amyloidosis.
- Active plasma cell leukemia.
- Red Blood Cell (RBC) and platelet transfusions and blood growth factors within 14 days of C1D1 (Arms 1-11 only). Red blood cells and platelet...
See the full eligibility criteria
Who can join
- Written informed consent signed in accordance with federal, local, and institutional guidelines.
- Age greater than or equal to (≥) 18 years at the time of informed consent.
- Histologically confirmed diagnosis with measurable disease for relapsed/refractory myeloma.
- Symptomatic MM, based on IMWG guidelines.
- Patients must have measurable disease as defined by at least one of the following:
- Serum M-protein ≥ 0.5 gram per deciliter (g/dL) by serum protein electrophoresis (SPEP) or, for immunoglobulin A (IgA) myeloma, by quantitative IgA
- Urinary M-protein excretion at least 200 mg/24 hours
- Serum free light chain (FLC) ≥ 100 milligram per liter (mg/L), provided that FLC ratio is abnormal
- If SPEP is felt to be unreliable for routine M-protein measurement (example, for IgA MM), then quantitative immunoglobulin (Ig) levels by nephelometry or turbidometry are acceptable
- Any non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #22) that patients had from treatments in previous clinical studies must have resolved to less than or equal (≤)...
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
- Adequate hepatic function within 28 days prior to C1D1:
- For SPd, SRd, and SPEd: Total bilirubin \< 2\ upper limit of normal (ULN) (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3\ ULN) and both aspartate...
- For SVd, SPVd, SDd, SNd, SBd and SDPd: Total bilirubin of \< 1.5\ ULN (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3\ ULN) and both AST and ALT...
- For SKd and SMd: Total bilirubin \< 2x ULN (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3x ULN) and both AST and ALT \< 3.0x ULN
- Adequate renal function within 28 days prior to C1D1. For Arms 1-11, estimated creatinine clearance (CrCl) calculated using the formula of Cockroft and Gault (1976).
- ≥ 20 milliliter per minute (mL/min) for SVd, SDd, and SKd arms
- ≥ 30 mL/min for SNd, SBd, and SMd arms
- ≥ 45 mL/min for SPd, SPVd, SPEd and SDPd arms
- \> 60 mL/min for SRd arm
- Adequate hematopoietic function within 28 days prior to C1D1: absolute neutrophil count (ANC) ≥ 1,000/mm\^3, hemoglobin (Hb) ≥ 8.0 g/dL, and platelet count ≥ 100,000/mm\^3.
- SPVd (Arm 4) and SKd (Arm 6) only: platelet count ≥150,000.
- SMd (Arm 12) only: platelet count ≥75,000 for people in whom \<50% of bone marrow nucleated cells are plasma cells; or platelet count \<50,000 for people in whom ≥50% of bone marrow nucleated cells are plasma cells.
- Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients must use highly effective methods of contraception...
- Relapsed or refractory MM with:
- Documented evidence of progressive disease (PD) after achieving at least stable disease (SD) for ≥ 1 cycle during a previous MM regimen (i.e., relapsed MM)
- ≤ 25 percent (%) response (i.e., patients never achieved ≥ MR) or PD during or within 60 days from the end of the most recent MM regimen (i.e., refractory MM)
- Previously undergone ≥ 2 cycles of lenalidomide and a PI (in separate therapeutic regimens [not for maintenance] or in combination)
- In the expansion arm at RP2D, patients must not be pomalidomide refractory SVd (Arm 2) Only:
- Relapsed or refractory MM with:
- Documented evidence of relapse after ≥ 1 previous line of therapy
- Not refractory to bortezomib in their most recent line of therapy SRd in RRMM (Arm 3) Only:
- Patients who received ≥ 1 prior therapeutic regimen (prior lenalidomide is allowed as long as patient's MM was not refractory to prior lenalidomide; patients whose MM was refractory to lenalidomide maintenance regimens...
- Patients who received 1- 3 prior lines of therapy, including ≥ 2 cycles of lenalidomide and have demonstrated disease progression on their last therapy (may include prior bortezomib, as long as the patient's MM was not...
- Patients who received ≥ 3 prior lines of therapy, including a PI and an immunomodulatory agent (IMiD), or patients with MM refractory to both a PI and an IMiD.
- Patients must not have received prior anti-cluster of differentiation 38 (anti-CD38) monoclonal antibodies (Cohort 5.3 ONLY - Dose Expansion at RP2D). SKd (Arm 6) Only:
- Patients may have received prior PIs; however, their MM must NOT be refractory to carfilzomib. SRd in NDMM (Arm 7) Only:
- Patients must have symptomatic myeloma per IMWG guidelines with either CRAB criteria (calcium elevation, renal failure, anemia, lytic bone lesions) or myeloma-defining events and need systemic therapy. No prior systemic...
- Patients must have MM that relapsed after 1 - 3 prior lines of therapy (may not include those with MM refractory to bortezomib or carfilzomib but patients must be ixazomib-naïve). SPEd (Arm 9) Only:
- Patients who received ≥ 2 prior therapies, including lenalidomide and a proteasome inhibitor (in separate or the same regimens), but patients must be pomalidomide-naive and elotuzumab-naive in the Dose Expansion at RP2D...
- Patients who have MM that was refractory to an IMiD, a proteasome inhibitor, and refractory or intolerant (or both) to an anti-CD38 monoclonal antibody. Patients must be belantamab mafodotin-naive in the Dose Expansion...
- Patients who received 1-3 prior therapies, including lenalidomide and a proteasome inhibitor (in separate or the same regimen), but patients must be pomalidomide-naive and daratumumab-naive in the Dose Expansion cohort...
- Patients with RRMM who have received at least 2 prior lines of therapy, including an IMiD, a PI, and an anti-CD38 monoclonal antibody. Patients must have either failed a T-cell redirecting treatment (eg, CAR-T or...
What rules you out
- Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:
- Smoldering MM.
- MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead.
- Documented active systemic amyloid light chain amyloidosis.
- Active plasma cell leukemia.
- Red Blood Cell (RBC) and platelet transfusions and blood growth factors within 14 days of C1D1 (Arms 1-11 only). Red blood cells and platelet transfusions and blood growth factors within 7 days of C1D1 (Arm 12).
- Platelet transfusion or G-CSF within 7 days or pegfilgastrim within 14 days prior to the complete blood count (CBC) used to determine eligibility.
- Radiation, chemotherapy, or immunotherapy or any other tumor-directed therapy ≤ 2 weeks prior to C1D1, and radio-immunotherapy within 6 weeks prior to C1D1. Patients on long-term glucocorticoids during Screening do not...
- Patients with history of spinal cord compression with residual paraplegia (Dose Escalation Phase only).
- Treatment with an investigational anti-cancer therapy within 3 weeks prior to C1D1.
- Prior autologous stem cell transplantation \< 1 month, or allogeneic stem cell transplantation \< 3 months prior to C1D1.
- Active graft versus host disease after allogeneic stem cell transplantation.
- Life expectancy \< 3 months.
- Major surgery within 4 weeks prior to C1D1.
- Active, unstable cardiovascular function:
- Symptomatic ischemia, or
- Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left...
- Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or
- Myocardial infarction (MI) within 3 months prior to C1D1
- Ejection fraction (EF) \< 50% at Screening (Arms 1-11 only, screening echocardiogram not required for Arm 12, SMd)
- Uncontrolled active hypertension (Arms 1-11 only).
- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose.
- Known active hepatitis A, B or C.
- Known human immunodeficiency virus (HIV) infection or HIV seropositivity.
- Any active gastrointestinal dysfunction that prevents the patient from swallowing tablets or interferes with absorption of study treatment.
- Currently pregnant or breastfeeding.
- A serious active psychiatric or active medical condition which, in the opinion of the Investigator, could interfere with treatment.
- Hypersensitivity to any of the treatments for the arm in which the patient is enrolled.
- SVd Arm (Arm 2), SPVd (Arm 4), and SNd Arm (Arm 8) only: Prior history of neuropathy Grade \> 2, or Grade ≥ 2 neuropathy with pain at Screening (within 28 days prior to C1D1).
- Patients who are eligible for the selinexor PK Run-in only: Treatment with moderate or strong inhibitors/inducers of CYP3A within 7 days prior to Day 1 of the PK Run-in period.
- Patients who are eligible for the selinexor PK Run-in only: Not able to receive a strong CYP3A4 inhibitor due to concomitant medications.
- SKd arm only: HBs Ag + plus HBc Ab + even though no active hepatitis B virus (HBV) hepatitis. If HBs Ag - plus HBc Ab +, treating physician needs to contact the medical monitor.
- Prior exposure to a selective inhibitor of nuclear export (SINE) compound, including selinexor. SBd (Arm 10): Only:
- Current corneal epithelial disease except mild punctate keratopathy. SMd (Arm 12 only):
- History of allogeneic stem cell or solid organ transplant at any time.
- History of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide (including ≥Grade 3 rash during prior thalidomide, lenalidomide, or pomalidomide therapy), carfilzomib or dexamethasone, any CELMoD...
- Subject is unable or unwilling to agree to refrain from donating blood while on study intervention, during dose interruptions, and for at least 28 days following the last dose of study intervention.
- Subject is unable or unwilling to undergo protocol required thromboembolism prophylaxis.
- Use of strong CYP3A4 modulator or proton-pump inhibitors (eg, omeprazole, lansoprazole), within 2 weeks of starting study intervention.
- Active concomitant malignancies or history of another malignancy within 3 years prior to C1D1 except for adequately treated early-stage basal cell or squamous cell carcinoma of skin, adequately treated carcinoma in situ...
- History of chronic hepatitis B with detectable viral load.
- Subject is unable or unwilling to receive protocol-required dual antiemetic prophylaxis
The study team makes the final eligibility decision.
Where it's taking place
- Gilbert, Arizona, United States
- Los Angeles, California, United States
- Denver, Colorado, United States
- Boston, Massachusetts, United States
- Omaha, Nebraska, United States
- Hackensack, New Jersey, United States
- New York, New York, United States
- Rochester, New York, United States
- Chapel Hill, North Carolina, United States
- Durham, North Carolina, United States
- Nashville, Tennessee, United States
- Seattle, Washington, United States
- Madison, Wisconsin, United States
- Calgary, Alberta, Canada
- Edmonton, Alberta, Canada
- Vancouver, British Columbia, Canada
- Winnipeg, Manitoba, Canada
- St. John's, Newfoundland and Labrador, Canada
- Halifax, Nova Scotia, Canada
- Toronto, Ontario, Canada
+ 1 more site(s).
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Gilbert, Arizona, United States; Los Angeles, California, United States; Denver, Colorado, United States; Boston, Massachusetts, United States; Omaha, Nebraska, United States; Hackensack, New Jersey, United States and 15 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.