A Phase 1b/2 Study of Selinexor (KPT-330) in Combination with Backbone Treatments for Relapsed/Refractory Multiple Myeloma

Clinical Trial Details

This study will independently assess the efficacy and safety of 8 combination therapies in 9 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)
  • 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)
  • Arm 5: Selinexor + dexamethasone + daratumumab (SDd); enrollment complete
  • Arm 6: Selinexor + dexamethasone + carfilzomib (SKd)
  • Arm 7: Selinexor + dexamethasone + lenalidomide (SRd) in NDMM
  • Arm 8: Selinexor + dexamethasone + ixazomib (SNd)
  • Arm 9: Selinexor + dexamethasone + pomalidomide + elotuzumab (SPEd)

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) 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.

Key Eligibility: 

Inclusion Criteria

  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Age ≥ 18 years at the time of informed consent
  • Histologically confirmed diagnosis with measurable disease for relapsed/refractory myeloma
  • Symptomatic MM for NDMM needing therapy, based on IMWG guidelines
  • Patients must have measurable disease 
  • 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 ≤ Grade 2 by Cycle 1 Day 1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
  • Adequate hepatic function within 28 days prior to C1D1
  • Adequate renal function within 28 days prior to C1D1. Estimated creatinine clearance (CrCl) calculated using the formula of Cockroft and Gault (1976)
  • Adequate hematopoietic function within 28 days prior to C1D1: total white blood cell (WBC) count ≥ 1,500/mm³, ANC ≥ 1,000/mm³, hemoglobin (Hb) ≥ 8.0 g/dL, and platelet count ≥ 150,000/mm³
  • 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 1 week following the last dose of study treatment.

Exclusion Criteria

  • 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
  • Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to C1D1, and radio-immunotherapy within 6 weeks prior to C1D1. Patients on long-term glucocorticoids during Screening do not require a washout period. Prior radiation is permitted for treatment of fractures or to prevent fractures as well as for pain management
  • Patients with history of SCC 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 less than 1 month, or allogeneic stem cell transplantation less than 3 months prior to C1D1
  • Active graft versus host disease after allogeneic stem cell transplantation
  • Life expectancy less than 3 months
  • Major surgery within 4 weeks prior to C1D1
  • Active, unstable cardiovascular function
  • Uncontrolled active hypertension
  • Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
  • Known active hepatitis A, B or C
  • Known 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 psychiatric or 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
  • Prior exposure to a SINE compound, including selinexor
  • In the SVd Arm (Arm 2), SPVd (Arm 4), and SNd Arm (Arm 8) only: Prior history of neuropathy Grade greter than 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. Not able to receive a strong CYP3A4 inhibitor due to concomitant medications
  • SKd Arm only: HBs Ag + plus HBc Ab + even though no active HBV hepatitis. If HBs Ag - plus HBc Ab +, treating physician needs to contact the medical monitor

Study contact by location

Upper East Side - Manhattan

Contact(s)

Kathleen Pogonowski, RN
(646) 962-6500
kap9111@med.cornell.edu

Primary Investigator(s)

Protocol ID(s)

Weill Cornell Medicine IRB #:

1803019113

ClinicalTrials.gov:

NCT02343042

Sponsor:

KCP-330-017

Status

Open to Enrollment

Age Group

Adult

Sponsor