A Study of Evaluating the Safety and Efficacy of ATG-010 in Relapsed Refractory Multiple Myeloma
Condition: Relapse/Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: ATG-010
Intervention description: ATG-010 (Selinexor) will be given at an oral fixed milligram (mg) dose of 80 mg twice weekly each week for four-week cycles (total of 8 ATG-010 doses per cycle).
Dexamethasone 20 mg will be given with each dose of ATG-010 (Selinexor)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 82.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is an open-label, single-arm study of ATG-010 (selinexor) plus low-dose Dexamethasone
      (Sd) in patients with multiple myeloma previously treated with lenalidomide and bortezomib
      refractory to prior treatment with immunomodulatory agents and proteasome Inhibitors.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent in accordance with federal, local, and institutional
             guidelines.

          2. Age ≥ 18 years at the time of signing informed consent.

          3. Patients must have previously received including proteasome inhibitors (PI) (i.e.,
             lenalidomide) and immunomodulatory drugs (i.e., bortezomib) and were refractory to
             both drugs.

          4. Any clinically significant non-hematological toxicities (except for peripheral
             neuropathy as described in exclusion criterion #17) that patients experienced from
             treatments in previous clinical studies must have resolved to Grade ≤ 2 by Cycle 1 Day
             1.

          5. Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin < 2x
             upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a
             total bilirubin of < 3x ULN), AST < 2.5x ULN and ALT < 2.5x ULN.

          6. Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine
             clearance of ≥ 20 mL/min, calculated using the formula of cockroft and gault.

          7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

          8. Measurable MM based on IMWG guidelines.

          9. Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See Exclusion
             Criterion #20 for transfusion washout periods for RBCs and platelets):

               1. Hemoglobin level ≥ 8.5 g/dL

               2. ANC ≥ 1000/mm^3

               3. Platelet count ≥ 75,000/mm^3 (patients in whom < 50% of bone marrow nucleated
                  cells are plasma cells) or ≥ 50,000/mm^3 (patients in whom ≥ 50% of bone marrow
                  nucleated cells are plasma cells. [Platelet transfusions < 1 week prior to Cycle
                  1 Day 1 are prohibited (see below).]

         10. Female subjects of child-bearing potential must have both of the following:

               1. Agree to the use of two study physician-approved contraceptive methods
                  simultaneously, or practice complete abstinence starting at the time of ICF
                  signature, while on study medication, and 3 months following the last dose of
                  study drug.

               2. Have negative serum pregnancy test result at screening.

        Exclusion Criteria:

          -  The presence of any of the following will exclude a subject from enrollment:

               1. Active smoldering MM.

               2. Active plasma cell leukemia.

               3. Documented systemic amyloid light chain amyloidosis.

               4. Active central nervous system (CNS) MM.

               5. Pregnancy or breastfeeding.

               6. Chemotherapy ≤ 4 week, radiation and immunotherapy ≤ 4 weeks prior to Cycle 1 Day
                  1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day 1.

               7. Active graft vs. host disease (after allogeneic stem cell transplantation) at
                  Cycle 1 Day 1

               8. Life expectancy of < 4 months.

               9. Major surgery within four weeks prior to Cycle 1 Day 1.

              10. Active, unstable cardiovascular function:

                    1. Symptomatic ischemia, or

                    2. 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

                    3. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥
                       3, or

                    4. Myocardial infarction (MI) within 3 months prior to Cycle 1 Day 1.

              11. Prior exposure to a SINE compound, including ATG-010.