Ensayos clínicos

Inclusion Criteria:

• Subjects must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
• Adult male or female, ≥ 18 years old.
• Laboratory values meeting the following criteria within the screening period prior to the first dose of study drug:
  • Absolute neutrophil count (ANC) ≥ 1000/μL.  Subject may use growth factor support to achieve ANC eligibility criteria;
  • Platelets: ≥ 50,000/mm^3.  For subjects with > 50% myeloma involvement in the marrow, a platelet count of ≥ 30,000 mm^3 is allowed. Subjects may not have received a platelet transfusion within 72 hours prior to the platelet count used for eligibility;
  • Hemoglobin ≥ 8.0 g/dL; subject may receive red blood cell (RBC) transfusions in accordance with institutional guidelines to meet this criteria;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN);
  • Total bilirubin ≤ 1.5 × ULN (subjects with documented Gilbert's syndrome may have bilirubin > 1.5 × ULN);
  • Creatinine Clearance (CrCl) ≥ 30 mL/min, measured by 24-hour urine collection or calculated using the Cockcroft-Gault formula;
  • Serum calcium corrected for albumin ≤ 14.0 mg/dL (≤ 3.5 mmol/L).
• Are willing or able to comply with procedures required in this protocol.
• Are willing and able to receive antithrombotic prophylactic treatment. Documented diagnosis of MM based on standard IMWG criteria.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Subject has documented disease progression on or within 60 days of completion of their last therapy. 
• Subject has received at least 2 prior lines of therapy. 
  • A line of therapy consists of at least 1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens.
• Subject must have received at least 2 consecutive cycles of lenalidomide and be refractory to lenalidomide as defined by one of the following:
  • Subject experienced PD on or within 60 days of completing treatment;
  • Subject exhibited PR or better but relapsed within 6 months after stopping treatment.
• Subject must have received at least 2 consecutive cycles of a proteasome inhibitor (bortezomib, carfilzomib or ixazomib).
• Subject has measurable disease at Screening, defined by at least 1 of the following:
  • Serum M-protein ≥ 1.0 g/dL (≥ 10 g/L); OR
  • Urine M-protein ≥ 200 mg/24 hours; OR
  • Serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL (100 mg/L), provided serum FLC ratio is abnormal.
• Subject has MM positive for t(11;14) as determined by an analytically validated fluorescent in situ hybridization (FISH) assay per centralized laboratory testing.
• No history of treatment with venetoclax or another BCL-2 inhibitor or pomalidomide.
• No history of other active malignancies, including myelodysplastic syndromes (MDS), within the past 3 years with the following exceptions:
  • Adequately treated in situ carcinoma of the cervix uteri or the breast;
  • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
  • Prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment; or
  • Previous malignancy with no current evidence of disease, and which was confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study.
• No evidence of ongoing graft-versus-host disease (GvHD) if prior stem cell transplant (SCT).
• No prior treatment with any of the following:
  • Allogeneic or syngeneic SCT within 16 weeks prior to randomization; or
  • Autologous SCT within 12 weeks prior to randomization.
• No known meningeal involvement of MM.
• No history of clinically significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, pulmonary or hepatic disease within the last 6 months that, in the Investigator's opinion, would adversely affect the subject's participation in the study.
• No history of known allergies, hypersensitivities, or intolerance to any of the study drug or excipients, or thalidomide derivatives.
• None of the following conditions:
  • Nonsecretory MM;
  • Active plasma cell leukemia; i.e., either 20% of peripheral white blood cells or > 2.0 × 10^9/L circulating plasma cells by standard differential;
  • Waldenström's macroglobulinemia;
  • Primary amyloidosis;
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes);
  • Known human immunodeficiency virus (HIV) infection;
  • Active hepatitis B or C infection based on screening blood testing;
  • Significant cardiovascular disease, including uncontrolled angina, arrhythmia, recent myocardial infarction within 6 months of first dose, congestive heart failure New York Heart Association (NYHA) Class ≥ 3;
  • Major surgery within 4 weeks prior to first dose or planned during study participation;
  • Acute infections within 14 days prior to first dose of study drug requiring therapy (antibiotic, antifungal, or antiviral);
  • Uncontrolled diabetes or hypertension within 14 days prior to first dose; or
  • Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to first dose.
• A negative serum pregnancy test for all female subjects (except those of non-childbearing potential) within 10 to 14 days prior to initiating therapy and a negative urine pregnancy test within 24 hours for all female subjects (except those of non-childbearing potential) at baseline prior to the first dose of study drug.
• If female, subject must be either postmenopausal, OR permanently surgically sterile OR for women of childbearing potential practicing at least 2 protocol-specified methods of birth control that are effective from at least 30 days before starting study drugs through at least 30 days after the last dose of any study drug.
• If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree, from Study Day 1 through 30 days after the last dose of study drug, to practice the protocol-specified contraception.
• Female who is not pregnant, breastfeeding, or considering becoming pregnant during the study and for at least 30 days after the last dose of study drug.
• Male who is not considering fathering a child or donating sperm and/or semen during the study and for at least 30 days after the last dose of study drug.
• Subject must not have been treated with any systemic anti-myeloma therapies within 5 half-lives or 2 weeks prior to randomization, whichever is longer (or 2 weeks if half-life unknown), and through the last dose of  any study drug. For anti-myeloma monoclonal antibodies, subjects should observe a washout period of 30 days prior to randomization.
• Subject must not have been treated with anti-myeloma radiotherapy within 2 weeks prior to randomization.
• Subject must not have received corticosteroid therapy at a dose equivalent to > 4 mg daily of dexamethasone or a single dose of corticosteroid equivalent dose > 40 mg of dexamethasone within 2 weeks prior to randomization.
• Subject must not have used systemic strong or moderate inhibitor or inducer of cytochrome P450 (CYP)3A (Appendix B in the Operations Manual) within 1 week prior to the first dose of study drugs.
• Subject must not have used systemic strong inhibitor of CYP1A2 within 1 week before the first dose of study drugs.
• Subject must not have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or starfruit within 3 days prior to the first dose of study drugs.
• Subject must not have received any live vaccines within 8 weeks prior to randomization.
• Subject must not anticipate the use of prohibited medications or foods during study participation.

Exclusion Criteria:

• Anything other than a positive response to the questions below will result in exclusion from study participation.