STOMP: Selinexor and Backbone Treatments of Multiple Myeloma Patients
Study Details
Study Description
Brief Summary
This study will independently assess the efficacy and safety of 10 combination therapies in 11 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)
-
Arm 10: Selinexor + dexamethasone + belantamab mafodotin (SBd)
-
Arm 11: Selinexor + dexamethasone + pomalidomide + daratumumab (SDPd)
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
This is a multi-center, open-label, clinical study with Dose Escalation (Phase 1) and Expansion (Phase 2) to independently assess the MTD, efficacy , and safety of 10 combination therapies in 11 arms in patients with RRMM and NDMM. Patients will be assigned to treatment arms based on their diagnoses and treatment histories. For 9 patients, a PK Run-in period will precede Cycle 1 (DLT evaluation) to assess selinexor PK when co-administered with a strong CYP3A4 inhibitor. In the Dose Escalation Phase (Phase 1): (a) in Arm 1 (SPd), Arm 2 (SVd), and Arm 3 (SRd in RRMM), patients will be randomized to either QW or BIW selinexor dosing cohorts; (b) in Arm 5 (SDd), patients will be sequentially assigned in blocks of 3 to either QW or BIW selinexor dosing; (c) in Arm 4 (SPVd), Arm 6 (SKd), Arm 7 (Srd in NDMM), Arm 8 (SNd), Arm 9 (SPEd), Arm 10 (SBd), and Arm 11 (SDPd) patients will be assigned to QW selinexor dosing.
Cohort 1.4 is included from Version 10 to study safety and tolerability of SPd with selinexor 40 mg QW, is lower than RP2D (ie, selinexor 60 mg QW) in combination with pomalidomide 4 mg. Cohort 1.4 is a different expansion cohort from the one with RP2D (ie, Cohort 1.3). In Cohort 1.4, 20 patients will be enrolled in total.
Starting in protocol Version 8.0, patients enrolled to the Dose Escalation Phase of Arm 4 (SPVd), Arm 6 (SKd), Arm 8 (SNd), Arm 9 (SPEd), Arm 10 (SBd), and Arm 11 (SDPd) will first be enrolled to a 14-day PK Run-in period (selinexor +/- clarithromycin) until 9 patients have been enrolled. During this 14-day PK Run-in period, selinexor 40 milligrams (mg) will be administered alone on Day 1, clarithromycin 500 mg twice daily (BID) will be administered on Days 2-8, and selinexor 40 mg will again be administered on Day 8 with the morning clarithromycin dose. Blood samples for PK analysis will be collected pre-dose and 1 (± 10 min), 1.5 (± 10 min), 2 (± 10 min), 3 (± 10 min), 4 (± 10 min), 5 (± 10 min), 6 (± 10 min), 8 (± 10 min), and 24 h (± 30 min) hours after selinexor is dosed on Day 1 (without clarithromycin) and Day 8 (with clarithromycin). Patients will then proceed to the DLT evaluation period that will begin after the completion of the 14-day PK Run-in period; this day will be designated as Cycle 1 Day 1 (C1D1) in the Dose Escalation Phase.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1: Selinexor, Low-dose Dexamethasone and Pomalidomide (SPd) Each cycle is of 28 days Cohort 1.1: Selinexor (SEL) 60/80/100 mg orally (PO) once weekly (QW); Dexamethasone (DEX) 40 mg PO once weekly; Pomalidomide (POM) 2/3/4 mg PO Days 1-21. Cohort 1.2: SEL 40/60/80 mg PO twice weekly (BIW); DEX 20 mg PO twice weekly; POM 3/4 mg PO Days 1-21. Cohort 1.3: Selinexor, Dexamethasone and Pomalidomide will be dosed at RP2D-1. Cohort 1.4: SEL 40 mg PO QW; DEX 40 mg PO QW; POM 4mg PO once daily (QD) Days 1-21. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Pomalidomide
Oral tablets
Other Names:
|
| Experimental: 2: Selinexor, Low-dose Dexamethasone and Bortezomib (SVd) Each cycle is of 35 days Cohort 2.1: SEL 60/80/100 mg PO once weekly; DEX 40 mg PO once weekly; Bortezomib (BOR) 1.3 milligram per meter square (mg/m^2) subcutaneous (SC) once weekly. Cohort 2.2: SEL 40/60/80 mg PO twice weekly; DEX 20 mg PO twice weekly; BOR 1.3 mg/m^2 subcutaneous (SC) once weekly. Cohort 2.3: Selinexor, Dexamethasone and Bortezomib will be dosed at RP2D-2. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Bortezomib
Subcutaneous Injection (single use vial)
Other Names:
|
| Experimental: 3: Selinexor, Low-dose DEX, and Lenalidomide (SRd) in RRMM Each cycle is of 28 days Cohort 3.1: SEL 40/60/80/100 mg PO once weekly; DEX 40 mg PO once weekly; Lenalidomide (LEN) 15/25 mg PO Days 1-21. Cohort 3.2: SEL 40/60/80 mg PO twice weekly; DEX 20 mg PO twice weekly; LEN 15/25 mg PO Days 1-21. Cohort 3.3: Selinexor, Dexamethasone and Lenalidomide will be dosed at RP2D-3. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Lenalidomide
Oral capsule
Other Names:
|
| Experimental: 4:Selinexor, Low-dose dexamethasone, Pomalidomide, Velcade (SPVd) PK Run-in Period: Selinexor and Clarithromycin: For the first 9 patients enrolled into this dose escalation arm 14 day run-in period after which patients will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-escalation Phase: All patients enrolled into this Arm Each cycle is of 28 days. Cohort 4.1: SEL 40/60 mg PO once weekly; DEX 40 mg PO once weekly; POM 4 mg PO Days 1-21; BOR 1.3 mg/m^2 subcutaneous (SC) once weekly. Cohort 4.3: Selinexor, Dexamethasone, Pomalidomide, Velcade (Bortezomib) will be dosed at RP2D-4. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Pomalidomide
Oral tablets
Other Names:
Drug: Bortezomib
Subcutaneous Injection (single use vial)
Other Names:
Drug: Clarithromycin
Tablets
Other Names:
|
| Experimental: 5: Selinexor, Low-dose dexamethasone, and Daratumumab (SDd) Each cycle is of 28 days Cohort 5.1: SEL 80/100 mg PO once weekly; DEX 40 mg once weekly (IV or PO); DARA: 16 mg/kg IV infusion Cycle 1-2: Once weekly, Cycle 3-6: Every other week, Cycle 6 and greater: Once a month. Cohort 5.2: SEL: 60 mg PO twice weekly; DEX: 40 mg weekly (IV or PO); DARA: 16 milligram per kilogram (mg/kg) IV infusion Cycle 1-2: Once. weekly, Cycle 3-6: Every other week, Cycle 6 and greater: Once a month. Cohort 5.3: Selinexor, Dexamethasone and Daratumumab will be dosed at RP2D-5. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Daratumumab
Intravenous Infusion
Other Names:
|
| Experimental: 6: Selinexor, Low-dose dexamethasone, and Carfilzomib (SKd) PK Run-in Period: Selinexor and Clarithromycin: For the first 9 patients enrolled into this dose escalation arm 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-Escalation Phase: All patients enrolled into this Arm Each cycle is of 28 days Cohort 6.1: SEL 40/60/80/100 mg PO once weekly on days 1, 8, 15, and 22; DEX 40 mg IV or PO once weekly; Carfilzomib (CAR) 56 or 70 mg/m^2 IV infusion once weekly on days 1, 8, and 15. Cohort 6.2: SEL 60/80/100 mg PO once weekly on days 1, 8, and 15; DEX 40 mg IV or PO once weekly; CAR 56 or 70 mg/m^2 IV infusion once weekly on days 1, 8, and 15. Cohort 6.3: Selinexor, Dexamethasone and Carfilzomib will be dosed at RP2D-6. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Carfilzomib
Intravenous infusion
Other Names:
Drug: Clarithromycin
Tablets
Other Names:
|
| Experimental: 7: Selinexor, Low-dose DEX and Lenalidomide (SRd) in NDMM Each cycle is of 28 days Cohort 7.1: SEL 40/60/80 mg PO once weekly; DEX 40 mg PO once weekly; LEN 25 mg PO Days 1-21. Cohort 7.3: Selinexor, Dexamethasone and Lenalidomide will be dosed at RP2D-7. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Lenalidomide
Oral capsule
Other Names:
|
| Experimental: 8: Selinexor, Low-dose dexamethasone, and Ixazomib (SNd) PK Run-in Period: Selinexor & Clarithromycin: For the first 9 patients enrolled into this dose escalation arm 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-Escalation Phase: All patients enrolled into this Arm Each cycle is of 28 days Cohort 8.1: SEL 40/60/80/100 mg PO once weekly; DEX 20 mg PO twice weekly; IXA 3/4 mg PO once weekly. Cohort 8.3: Selinexor, Dexamethasone and Ixazomib will be dosed at RP2D-8. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Ixazomib
Oral capsule
Other Names:
Drug: Clarithromycin
Tablets
Other Names:
|
| Experimental: 9: Selinexor, Low-dose DEX, Pomalidomide and Elotuzumab (SPEd) PK Run-in Period: Selinexor and Clarithromycin: For the first 9 patients enrolled into this dose escalation arm 14 day run-in period after which patient will proceed to Dose-Escalation Phase C1D1 Selinexor 40 mg will be dosed on Days 1 and 8. Clarithromycin 500 mg will be dosed twice daily on Days 2-8. PK samples will be collected on Days 1 and 8 at 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post dose. Dose-Escalation Phase: All patients enrolled into this Arm Each cycle is of 28 days Cohort 9.1: SEL 20/40/60 mg PO once weekly; DEX 28/20 mg PO twice weekly; POM 4 mg PO QD Days 1-21; Elotuzumab (ELO) 10/20 mg/kg IV will be given once weekly on Days 1,8, 15 and 22 of Cycles 1-2. Starting on Cycle 3 and continuing for future cycles, elotuzumab will be dosed at 20 mg/kg on Day 1 of each cycle only. Cohort 9.3: Selinexor, Dexamethasone, Pomalidomide and Elotuzumab will be dosed at RP2D-9. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Pomalidomide
Oral tablets
Other Names:
Drug: Elotuzumab
Intravenous infusion
Other Names:
|
| Experimental: 10. Selinexor, Dexamethasone, and Belantamab Mafodotin (SBd) Each cycle is of 21 days Cohort 10.1: SEL 40/60/80 mg PO once weekly on Days 1, 8, and 15; DEX 40 mg PO QW on Days 1, 8, and 15; Belantamab Mafodotin (BEL) 2.5 mg/kg IV infusion every 3 weeks (Q3W) Day 1 of each cycle. Cohort 10.3: Selinexor, Dexamethasone, and Belantamab Mafodotin will be dosed at RP2D-10. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Belantamab Mafodotin
Intravenous infusion
Other Names:
|
| Experimental: 11. Selinexor, Dexamethasone, Pomalidomide, and Daratumumab (SDPd) Each Cycle is of 28 days Cohort 11.1 SEL 40/60 mg PO once weekly on Days 1, 8, and 15; DEX total 40 mg weekly (IV or PO) single or divided doses on Days 1, 8, 15, and 22; POM 4 mg PO QW Days 1-21; DARA 16 mg/kg IV or SC QW on Days 1, 8, 15 and 22 of Cycles 1-2 and on Days 1 and 15 of Cycles 3-6, Day 1 of every Cycle greater than (>6). Cohort 11.3 Selinexor, Dexamethasone, Pomalidomide, and Daratumumab will be dosed at RP2D-11. |
Drug: Selinexor
Oral tablets
Other Names:
Drug: Dexamethasone
Oral tablets
Other Names:
Drug: Pomalidomide
Oral tablets
Other Names:
Drug: Daratumumab
Intravenous Infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase 1 (Dose-escalation): Maximum Tolerated Dose (MTD) [12 months]
MTD for once weekly and twice weekly selinexor dose cohorts in the 11 Arms will be evaluated.
- Phase 1 (Dose-escalation): Recommended Phase-2 dose (RP2D) [12 months]
RP2D for each Arm will be determined.
- Phase 1 (Dose-escalation): Maximum Plasma Concentration (Cmax) of Selinexor [Pre-dose, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post-dose on Day 1 (without clarithromycin) and Day 8 (with clarithromycin)]
Cmax of selinexor over a dosing interval when given with and without clarithromycin.
- Phase 1 (Dose-escalation): Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) of Selinexor [Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post-dose on Day 1 (without clarithromycin) and Day 8 (with clarithromycin)]
Total exposure of selinexor in the blood (AUC0-last) from the time of dosing to the last measurable concentration collected when given with and without clarithromycin.
- Phase 1 (Dose-escalation): Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) (AUC0-inf) [Pre-dose, 1, 1.5, 2, 3, 4, 5, 6, 8, and 24 hours post-dose on Day 1 (without clarithromycin) and Day 8 (with clarithromycin)]
- Phase 2 (Expansion): Overall response rate (ORR) [12 months]
ORR for each Arm independently. ORR to include stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR), according to the International Myeloma Working Group (IMWG) criteria.
- Phase 2 (Expansion): Duration of response (DOR) [12 months]
Duration of response for each Arm. DOR is defined as the number of days from the date of the first evidence of objective response until progression.
- Phase 2 (Expansion): Clinical Benefit Rate (CBR) [12 months]
CBR is defined the point estimate of the percentage of patients in that arm who have a response of sCR, CR, VGPR, PR or Minimal response (MR), as assessed by IMWG criteria.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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 (≤) Grade 2 by C1D1.
-
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 aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5* ULN
-
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 < 2.0* ULN
-
For SKd: Total bilirubin < 2* ULN (except patients with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of ≤ 3* ULN) and both AST and ALT < 3.0* ULN
- Adequate renal function within 28 days prior to C1D1. 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 and SBd 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: total white blood cell (WBC) count ≥ 1,500/millimeter cube (mm3), absolute neutrophil count (ANC) ≥ 1,000/mm3, 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.
- 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 throughout the study and for 1 week following the last dose of study treatment.
SPd (Arm 1) Only:
-
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 will be allowed in this cohort).
SPVd (Arm 4) Only:
- 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 refractory to bortezomib therapy), but patients must be pomalidomide-naïve in the Dose Expansion at RP2D (Cohort 4.3 ONLY).
SDd (Arm 5) Only:
-
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 therapy for NDMM is permitted other than pulse dose dexamethasone (maximum dose of 160 mg) or corticosteroid equivalent.
SNd (Arm 8) Only:
- 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 (Cohort 9.3 ONLY).
SBd (Arm 10) Only:
- 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 cohort at RP2D (Cohort 10.3 ONLY).
SDPd (Arm 11) Only:
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 at RP2D (Cohort 11.3 ONLY).
Exclusion Criteria:
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.
-
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 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 anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
-
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
-
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 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Banner MD Anderson Cancer Center | Gilbert | Arizona | United States | 85234 |
| 2 | Jonnsson Comprehensive Cancer Center / University of Los Angeles | Los Angeles | California | United States | 0095 |
| 3 | Sarah Cannon-Colorado Blood Cancer Institute | Denver | Colorado | United States | 80218 |
| 4 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 5 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 6 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 7 | Hackensack University Medical Center - John Theurer Cancer Center | Hackensack | New Jersey | United States | 07601 |
| 8 | Columbia University | New York | New York | United States | 10032 |
| 9 | Weill Cornell Medicine | New York | New York | United States | 10065 |
| 10 | Wilmot Cancer Center/ University of Rochester | Rochester | New York | United States | |
| 11 | University of North Carolina - Chapel Hill Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
| 12 | Duke Institute of Cancer/ Duke University | Durham | North Carolina | United States | 27710 |
| 13 | Sarah Cannon- Tennessee Oncology Nashville | Nashville | Tennessee | United States | 37203 |
| 14 | Swedish Cancer Institute | Seattle | Washington | United States | 98109 |
| 15 | University of Wisconsin School of Medicine and Public Health | Madison | Wisconsin | United States | 53792 |
| 16 | Tom Baker Cancer Center/Alberta Health Services | Calgary | Alberta | Canada | T2N 4Z6 |
| 17 | Cross Cancer Institute / University of Alberta | Edmonton | Alberta | Canada | T6G 1Z2 |
| 18 | Vancouver General Hospital | Vancouver | British Columbia | Canada | V5Z 1M9 |
| 19 | Cancer Care Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 20 | Memorial Hospital of Newfoundland | St. John's | Newfoundland and Labrador | Canada | A1B 3V6 |
| 21 | Queen Elizabeth II Health Sciences Center | Halifax | Nova Scotia | Canada | B3H 2Y9 |
| 22 | Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G 2M9 |
| 23 | Maisonneuve-Rosemont Hospital | Montreal | Quebec | Canada | H1T 2M4 |
| 24 | Royal Victoria Hospital / McGill University | Montreal | Quebec | Canada | H3A 1A1 |
Sponsors and Collaborators
- Karyopharm Therapeutics Inc
Investigators
- Study Director: Michael Kauffman, MD, Ph.D, Karyopharm Therapeutics Inc
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KCP-330-017