Clinical trial NCT02189343 (phase 1, status: completed)
Conditions: multiple myeloma
ICD codes: C90.01, C90.02, C90.00
Drugs: acy-1215 in combination with pomalidomide and dexamethasone
SMILES: [H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C
Eligibility criteria:

        Key Inclusion Criteria Includes:

        Patients meeting all of the following criteria may be enrolled in the study:

          1. Must be able to understand and voluntarily sign an ICF.

          2. Must be registered into the mandatory POMALYST Risk Evaluation and Mitigation Strategy
             (REMS)™ program, and be willing and able to comply with the requirements of the
             POMALYST REMS™ program (Appendix 9.3).

          3. Must be ≥ 18 years of age at the time of signing the ICF.

          4. Must be able to adhere to the study visit schedule and other protocol requirements.

          5. Must have a documented diagnosis of MM and have relapsed or relapsed and refractory
             disease. Patients must have received at least 2 lines of prior therapies. Patients
             must have relapsed after having achieved at least stable disease for at least 1 cycle
             of treatment to at least 1 prior regimen and then developed PD. Relapsed and
             relapsed-and-refractory patients must have documented evidence of PD during or within
             60 days (measured from the end of the last cycle) of completing treatment with the
             last antimyeloma drug regimen used just prior to study entry.

          6. Patients must have undergone prior treatment with at least 2 cycles of lenalidomide
             and at least 2 cycles of a proteasome inhibitor (either in a separate regimen or
             within the same regimen.

          7. Must not be a candidate for autologous stem cell transplant (ASCT), have declined the
             option of ASCT, or have relapsed after prior ASCT.

          8. Must have measurable levels of myeloma paraprotein in serum (≥ 0.5 g/dL) or urine (≥
             0.2 g/24 hours). Patients who do not have myeloma paraprotein must have serum free
             light chain (SFLC) concentration of ≥ 10 mg/dL, provided SFLC ratio is abnormal.
             Nonsecretory myeloma is excluded.

          9. Must have Eastern Cooperative Oncology Group performance status score of 0, 1, or 2.

         10. Females of childbearing potential must have a negative serum or urine pregnancy test
             as described in Appendix 9.3 for the POMALYST REMS™ program. Females of childbearing
             potential and males must either commit to continued abstinence from heterosexual
             intercourse or must abide by birth control requirements as described in Appendix 9.3
             for the POMALYST REMS™ program.

         11. Must agree to refrain from donating blood while on study drug and for 28 days after
             discontinuation from this study.

         12. Must agree not to share study medication with another person.

         13. Must be able to take ASA (81 or 325 mg) daily as prophylactic anticoagulation.
             Patients intolerant to ASA may use low molecular weight heparin. Lovenox is
             recommended. Coumadin will be allowed provided the patient is fully anticoagulated,
             with an international normalized ratio of 2 to 3.

        Key Exclusion Criteria Includes:

        Patients meeting any of the following criteria will be excluded from enrollment in the
        study:

          1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the patient from signing the ICF or from following the study
             requirements.

          2. Pregnant or lactating females.

          3. Prior therapy with histone deacetylase inhibitor or pomalidomide.

          4. Any of the following laboratory abnormalities:

               -  ANC < 1,000/µL

               -  Platelet count < 75,000/ µL for patients in whom < 50% of bone marrow nucleated
                  cells are plasma cells, or a platelet count < 50,000 for patients in whom ≥ 50%
                  of bone marrow nucleated cells are plasma cells

               -  Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior red blood cell transfusion or
                  recombinant human erythropoietin use is permitted).

               -  Creatinine clearance < 45 mL/min according to Cockcroft-Gault formula. If
                  creatinine clearance calculated from the 24 hour urine sample is ≥ 45 mL/min,
                  patient will qualify for the trial.

               -  Serum glutamic oxaloacetic transaminase/aspartate aminotransferase, or serum
                  glutamic pyruvic transaminase/alanine aminotransferase > 3.0 × ULN

               -  Serum total bilirubin > 2.0 mg/dL

          5. Prior history of malignancies, other than MM, unless the patient has been free of the
             disease for ≥ 3 years. Exceptions include the following:

               -  Basal or squamous cell carcinoma of the skin

               -  Ductal carcinoma in situ; or cervical intraepithelial neoplasia

               -  Carcinoma of the prostate with a current prostate-specific antigen below the
                  upper limit of normal

          6. Corrected QT interval (QTc) using Fridericia's formula value > 480 msec at Screening;
             family or personal history of long QTc syndrome or ventricular arrhythmias including
             ventricular bigeminy at Screening; previous history of drug-induced QTc prolongation
             or the need for treatment with medications known or suspected of producing prolonged
             QTc intervals on electrocardiogram.

          7. Known human immunodeficiency virus, hepatitis B virus, and known or suspected active
             hepatitis C virus infection.

          8. Hypersensitivity to thalidomide, lenalidomide, pomalidomide, or dexamethasone (such as
             Steven Johnson Syndrome). Hypersensitivity, such as rash, that can be medically
             managed is allowable.

          9. Peripheral neuropathy ≥ Grade 2 despite supportive therapy.

         10. Radiotherapy or systemic therapy (standard or an investigational or biologic
             anticancer agent) within 14 days of initiation of study drug treatment.

         11. Current enrollment in another clinical trial involving treatment and/or receiving an
             investigational agent for any reason.

         12. Inability or unwillingness to comply with birth control requirements or any of the
             POMALYST REMS™ requirements per Appendix 9.3.