A Clinical Study to Assess the Safety and Activity of SRT501 Alone or in Combination With Bortezomib in Patients With Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: 5.0g SRT501; Bortezomib
Intervention description: 5.0g SRT501 will be supplied in clinical kits as a powder which will be reconstituted with vehicle and water into a liquid suspension. SRT501 will be administered orally as a liquid suspension for 20 consecutive days in each 21 day cycle.; Bortezomib (1.3 mg/m2) will be given as an intravenous solution in a 3-5 second push on Day 1, 4, 8 and 11 in every 21 day cycle.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study is to determine the safety and tolerability of SRT501 (5.0
      g) with or without concurrent bortezomib administration, when administered once daily in 21
      day cycles, in male and female subjects with Multiple Myeloma.

      The purpose is also to define objective response (ORR, CR, PR, MR, SD) and time to
      progression (TTP) of SRT501 with or without concurrent bortezomib administered concurrently
      in male and female subjects with Multiple Myeloma.

      In addition, 15 subjects will participate in a sub-study to assess the pharmacokinetics of
      SRT501.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must be male or female ≥ 18 years at the time of signing Informed Consent.

          -  Subject was previously diagnosed with Multiple Myeloma and has failed at least one
             prior treatment regimen for the disease.

          -  Subject must have measurable disease.

          -  Subjects must have relapsed or relapsed/refractory disease as defined in Appendix 4.

          -  Subject must have a life expectancy of greater than 6 months.

          -  Subject has an ECOG Performance status of 0 to 2 (Appendix 2).

          -  Subject has no prior history of HIV-1, HIV-2, Hepatitis B or C infection.

          -  Subject has a normal 12 lead ECG or an ECG with an abnormality considered to be
             clinically insignificant.

          -  Subject has the ability to communicate with the investigative site staff in a manner
             sufficient to carry out all protocol procedures as described.

          -  Subject must be able to adhere to the study visit schedule and other protocol
             requirements.

          -  Subject must understand and voluntarily sign an informed consent document.

          -  All subjects of reproductive potential must agree prior to study entry to use adequate
             contraception (hormonal or double barrier method of birth control; abstinence) for the
             duration of the study dosing and at least 12 weeks after completion of study drug.

          -  Adequate end organ function, defined as the following:

               -  Total bilirubin < 2 x ULN, unless attributable to Gilbert's disease

               -  ALT (SGPT) and AST (SGOT) < 2.5 x ULN

               -  Creatinine < 2.0 x ULN

               -  ANC > 0.5 x 10^9/L

               -  Platelets > 20,000 cells/mm3

        Exclusion Criteria:

          -  Intolerance to resveratrol, SRT501 or bortezomib or significant allergy to either
             compound, boron or mannitol or significant prior toxicity with either agent that would
             preclude the safe use of that agent. Prior therapy with either compound is permitted.

          -  Subjects with other active malignancy, with the exception of basal cell or squamous
             cell carcinoma of the skin.

          -  An uncontrolled intercurrent illness including, but not limited to, recent (≤ 6
             months), ongoing or active infection, symptomatic congestive heart failure, unstable
             angina pectoris, cardiac arrhythmia, acute diffuse infiltrative pulmonary or
             pericardial disease, or psychiatric illness/social situations that would limit
             compliance with study requirements.

          -  Subject with a history of or current gastro-intestinal diseases influencing drug
             absorption, with the exception of an appendectomy.

          -  Women who are breast-feeding, pregnant, expect to become pregnant during the course of
             the study, or are sexually active in a heterosexual relationship and are not using a
             medically acceptable double barrier method birth control. Confirmation that the
             subject is not pregnant must be established by a negative serum beta-hCG pregnancy
             test result obtained during the Screening period. Pregnancy testing is not required
             for post-menopausal or surgically sterilized women. Women relying solely on oral
             contraceptives for birth control are excluded.

          -  Subjects who have had chemotherapy or radiotherapy within 4 weeks prior to signing
             Informed Consent or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier.

          -  Subjects who are on any concurrent medications that may exhibit anti-neoplastic
             therapy, with the exception of < 10 mg of prednisone or equivalent as indicated for
             other medical conditions, or up to 100 mg of hydrocortisone as premedication for
             administration of certain medications or blood products.

          -  Subjects currently taking any investigational therapies and/or dietary supplements
             containing resveratrol.

          -  Subjects with peripheral neuropathy of Grade 2 or greater.

          -  Subjects with uncontrolled bleeding.

          -  Subjects with evidence of mucosal or internal bleeding and/or platelet refractory
             (i.e., unable to maintain a platelet count ≥ 20,000 cells/mm3).

          -  Subjects with a hemoglobin < 8.0 g/dL. Transfusions and/or EPO treatment are permitted
             in subjects who are potentially excluded by this criteria.

          -  Any condition, including laboratory abnormalities, that in the opinion of the
             Investigator, would preclude treatment.