Phase 2 Study of Cytokine Release Syndrome Prophylaxis With Infliximab for Teclistamab/Talquetamab Therapy in Patients With Relapsed/Refractory Myeloma
This phase II trial tests how well giving infliximab works for the prevention of cytokine release syndrome (CRS) during treatment with teclistamab or talquetamab in patients with multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). CRS and neurologic toxicity (damage to the nervous system which includes the brain, spinal cord, and nerves) are potential risks of treatment with talquetamab and teclistamab. CRS involves a release of a large amount of proteins into the bloodstream causing inflammation. This may cause changes in blood pressure and heartbeat, flu-like symptoms (nausea, fever, and chills), and/or affect the lung/liver/kidney function. It may also cause certain brain-related symptoms, such as dizziness, weakness, confusion, difficulty speaking, and/or decreased brain function (possible paralysis and/or coma). Infliximab is a drug that prevents the tumor necrosis factor-alpha (TNF-α) from working. TNF-α is a cytokine, or chemical messenger, that helps your immune system produce inflammation. Giving infliximab may work well for the prevention of cytokine release syndrome during treatment with teclistamab or talquetamab in patients with relapsed or refractory multiple myeloma.
• Patients 18 years of age or older with evidence of relapsed or refractory disease as defined by IMWG criteria and measurable disease as defined by any of the following:
‣ Serum M-protein ≥ 0.5 g/dl
⁃ Urine monoclonal protein ≥ 200 mg/24h
⁃ Involved free light chain (FLC) level ≥ 10mg/dl (≥ 100mg/l) and an abnormal serum free light chain ratio (\< 0.26, or \> 1.65)
• Patients must have had at least 4 prior lines of therapy including an immunomodulatory agent (IMID), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.
‣ Prior B-cell maturating antigen (BCMA) chimeric antigen receptor (CAR)-T is permitted but at least 6 months must have lapsed from CAR-T exposure
⁃ Prior tumor necrosis factor alpha (TNFα) inhibitor use for a concomitant condition (ex. Rheumatoid arthritis) is permitted but at least 6 months must have lapsed from exposure
• Patients must have hemoglobin ≥ 7g/dL
• Absolute neutrophil count (ANC) ≥ 1000/µL
• Platelets ≥ 50,000/µL
• Total bilirubin ≤ 1.5 X the upper limit of normal (ULN)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase \< 2.5 X the ULN
• Calculated creatinine clearance of ≥ 30ml/min using Modification of Diet in Renal Disease (MDRD) formula
• Patients must have adequate cardiac function as evidenced by:
‣ Left ventricular ejection fraction ≥ 30%; baseline echocardiography (ECHO) is not required if ECHO was done within the preceding 6 months and patients do not have new signs/symptoms suggestive of heart failure
⁃ No uncontrolled arrhythmias
⁃ No New York Heart Association class III-IV heart failure
⁃ 12-lead electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec
• Negative test result for latent tuberculosis at screening
• Patients must provide informed consent
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤ 2
• Fertility requirements
‣ Women of child bearing potential (WOCBP) must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device \[IUD\], hormonal \[birth control pills, injections, hormonal patches, vaginal rings or implants\] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing and continue to 6 months after study treatment ending or teclistamab/talquetamab ending, whichever is longer. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy
⁃ Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy
⁃ A negative pregnancy test will be required for all WOCBP at screening and within 24 hours before starting treatment drugs, and with each cycle
⁃ Breast feeding is not permitted
⁃ Male patients must agree to use an adequate method of contraception (latex or synthetic condom) for the duration of the study and up to 6 months after study treatment ending
⁃ Criteria also applies to azoospermic males
⁃ Males should refrain from sperm donation during this time and continue for 6 months after study treatment ending