Bortezomib, selinexor and dexamethasone in patients with multiple myeloma.

Phase 1

• Conditions: Recidivant or refractory multiple myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-003957-14-IT
• Lead Sponsor: KARYOPHARM THERAPEUTICS, INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-15
• Last Update Posted: 18 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 364

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:
1. Histologically confirmed MM.
2. Had at least 1 prior anti-MM regimen and no more than 3 prior anti-MM regimens.
3. Documented evidence of progressive MM on or after their most recent regimen.
4. Prior treatment with bortezomib or other PI is allowed, provided all of the following
criteria are met:
a) Best response achieved with prior bortezomib at any time was = PR and with the last PI therapy (alone or in combination) was = PR, AND
b) Participant did not discontinue bortezomib due to Grade = 3 related toxicity, AND
c) Must have had at least a 6-month PI-treatment-free interval prior to C1D1 of study treatment.
5. Must have an ECOG Status score of 0, 1, or 2.
6. Written informed consent in accordance with federal, local, and institutional guidelines.
7. Age = 18 years.
8. Resolution of any clinically significant non-hematological toxicities.
9. Adequate hepatic function within 28 days prior to C1D10. Adequate renal function within 28 days prior to C1D1.
11. Adequate hematopoietic function within 7 days prior to C1D1.
12. Female patients of childbearing potential must agree to use 2 methods of contraception.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 124
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 240

Exclusion Criteria

Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:
1. Prior exposure to a SINE compound, including selinexor.
2. Prior malignancy that required treatment, or has shown evidence of recurrence (except
for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during
the 5 years prior to randomization. Cancer treated with curative intent for > 5 years
previously and without evidence of recurrence will be allowed.
3. Has any concurrent medical condition or disease (e.g., uncontrolled active hypertension,
uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with
study procedures.
4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals
within 1 week prior to C1D1. Patients on prophylactic antibiotics or with a controlled
infection within 1 week prior to C1D1 are acceptable.
5. Active plasma cell leukemia.
6. Documented systemic light chain amyloidosis.
7. MM involving the central nervous system.
8. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin
changes (POEMS) syndrome.
9. Spinal cord compression.
10. Greater than Grade 2 peripheral neuropathy or Grade = 2 peripheral neuropathy with pain
at baseline, regardless of whether or not the patient is currently receiving medication.
11. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
12. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy (including
investigational therapies) = 2 weeks prior to C1D1. Localized radiation to a single site at
least 1 week before C1D1 is permitted. Glucocorticoids within 2 weeks of C1D1 are
permitted. Patients on long-term glucocorticoids during Screening do not require a
washout period but must be able to tolerate the specified dexamethasone dose in this
study.
13. Prior autologous stem cell transplantation < 1 month or allogeneic stem cell
transplantation < 4 months prior to C1D1.
14. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.
15. Pregnant or breastfeeding females.
16. BSA < 1.4 m2 at baseline, calculated by the Dubois (Dubois and Dubois, 1916) or
Mosteller (Mosteller, 1987) method.
17. Life expectancy of < 4 months.
18. Major surgery within 4 weeks prior to C1D1.
19. Active, unstable cardiovascular function.
20. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.
21. 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.
22. 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.
23. 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.
24. Contraindication to any of the required concomitant drugs or supportive treatments.
25. Patients unwilling or unable to comply with the protocol, including providing 24-hour
urine samples for urine protein electrophoresis at the required time points.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified