A Phase I Study of Ganetespib +/- Bortezomib in Patients With Relapsed and/or Refractory Multiple Myeloma

Inclusion Criteria

• •Males or females, age 18 years or older.
• •Diagnosis of relapsed or refractory multiple myeloma (MM) and documentation of at least 2 prior therapies which must have included bortezomib and an immunomodulatory agent; there is no maximum number of prior regimens.
• •Patients with measurable disease defined as at least one of the following:
• •1. Serum M-protein ≥ 0.5 g/dl (≥ 5 g/l)
• •2. Urine M-protein ≥ 200 mg/24 h
• •3. Serum free light-chain (FLC) assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/l) and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65)
• •4. Measurable plasmacytoma (prior biopsy is acceptable, should be measured within 28 days of first study drug administration).
• •Subject has an Eastern Cooperative Oncology Group (ECOG) ≤ 2 OR Karnofsky ≥ 60% performance status.
• •Females of childbearing potential\*: Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. \*(FCBP - A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months).
• •Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).
• •Voluntary written informed consent before performance of any study-related procedure not part of routine medical care with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• •Inclusion clinical laboratories criteria
• •1. Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 10⁹/L) (Growth factors cannot be used within 7 days of first drug administration)
• •2. Platelet count ≥ 75 x 10⁹/L (platelet transfusions cannot be used within 4 days of first drug administration)
• •3. Hemoglobin ≥ 8.0 g/dl
• •4. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 1.5 x upper limit of normal (ULN)
• •5. Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 50 mL/min (Cockcroft-Gault calculation)
• •6. Total bilirubin ≤ 1.5 x ULN
• •7. Serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal (LLN) (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment).