Ensayos clínicos

Inclusion Criteria :

• Male or female patient ≥ 18 years of age.
• Patient has given voluntary written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time  without prejudice to their future medical care.
• Patient has been previously diagnosed with multiple myeloma (MM) based on standard criteria and currently requires treatment because MM has relapsed following a response, according to International Myeloma Working Group (IMWG) criteria.
• Patient had received at least two previous therapies including lenalidomide and proteasome inhibitor and have demonstrated disease progression on therapy or after completion of the last therapy.
• Patients with measurable disease defined as at least one of the following:
  • Serum M protein ≥ 0.5 g/dL (≥ 5 g/L);
  • Urine M protein ≥ 200 mg/24 hours.
• Serum free light chain (FLC) assay:
• Involved FLC assay ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal serum FLC ratio (< 0.26 or > 1.65).
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 – 14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide through 30 days after the last dose of pomalidomide and 5 months after the last dose of SAR650984. FCBP must also agree to ongoing pregnancy testing during the entire duration of treatment and monthly for 5 months after the last dose of SAR650984. Men must agree to use a latex or synthetic condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 30 days after the last dose of pomalidomide and 5 months after the last dose of SAR650984. These same patients must not donate sperm. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. All patients enrolled into this trial, must be registered in and must comply with all requirements of the POMALYST REMS program.
• † A female of childbearing potential (FCBP) is a sexually mature female who:
• 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Exclusion Criteria:

• Male or female patient < 18 years of age.
• Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status score > 2, or life expectancy ≤ 3 months.
• Clinical Laboratories Exclusion Criteria. Patients are excluded if the screening laboratory results are as follows:
  • Absolute neutrophil count (ANC) < 1000 cells/μl (1.0 x 109/L) (Growth factor cannot be used within the previous 7 days);
  • Aspartate aminotransferase (AST/SGOT) or Alanine aminotransferase (ALT/SGPT) ≥  2.5 x upper limit of normal (ULN);
  • Platelet count < 50 000 cells/μl (50 x 10^9/L) (without platelet transfusion in the previous 7 days);
  • Total bilirubin > 1.5 x ULN;
  • Calculated creatinine clearance (CrCl) < 30 mL/min (Cockcroft-Gault formula for Part A; MDRD equation for Part B);
  • Serum calcium (corrected for albumin) level above the ULN range (treatment of hypercalcemia is allowed and subject may enroll if hypercalcemia returns to normal with standard treatment).
• Primary refractory or intolerant to prior therapy with any anti-CD38 MoAb or had disease progression (after achieving a response of ≥ MR) during anti-CD38 MoAb, administered as last therapy.
• Prior therapy with pomalidomide until approval of amendment no. 02 only (after approval of amendment no. 02 these patients can be recruited in the study).
• Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
• Prior anti-cancer therapy within 14 days.
• Any >Grade 1 adverse reaction unresolved from previous treatments according to the NCI CTC AE v.4.03. The presence of alopecia or peripheral neuropathy ≤ Grade 2 without pain is allowed.
• Previous allogeneic stem cell transplantation with active Graft Versus Host Disease (GVHD) or being under immunosuppressive therapy in the last 2 months previously to the inclusion in the trial.
• Daily requirement for corticosteroids (equivalent to 10 mg /day prednisone for more than 7 consecutive days except for inhalation corticosteroids and patients being treated for adrenal insufficiency/replacement therapy).
• Patient is known to be human immunodeficiency virus (HIV) positive, Hepatitis B surface antigen-positive or active hepatitis C infection.
• Any clinically significant, uncontrolled medical conditions that, in the Investigator’s opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results.
• History of erythema multiforme or severe hypersensitivity to prior IMiD’s.
• Hypersensitivity or history of intolerance IMiDs, dexamethasone, sucrose, histidine (as base and hydrochloride salt) and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
• Inability to tolerate thromboprophylaxis.