Safety and Preliminary Efficacy Study of the Antibody PAT-SM6 in Patients With Relapsed or Refractory Multiple Myeloma

This is an interventional treatment trial for Drug Safety Read More

Inclusion Criteria:

• Male or female subjects ≥ 18 years of age
• Relapsed or refractory multiple myeloma defined as: Failure of at least 2 previous therapies including an immunomodulatory agent (thalidomide or lenalidomide) and a proteasome inhibitor (unless the subjects were not eligible or refused to receive those treatments), and with progressive disease, defined by an increase of serological or urine myeloma parameters by 25% to the last value
• Presence of serum M-protein ≥ 1 g per 100 mL (≥ 10 g/L) and/or urine M-protein ≥ 200 mg per 24-hour period and/or serum FLCs ≥ 10 mg per 100 mL (≥ 100 mg/L) combined with an abnormal ratio of lambda and kappa chains
• Life expectancy of > 6 months
• Karnofsky performance status ≥ 60%, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Absolute neutrophil count (ANC) ≥ 1.0 (1,000/mm3) and platelets ≥ 30 × 109/L without previous transfusion within the last 2 weeks before first study drug administration
• Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault equation)
• Total bilirubin ≤ 2 × upper normal limit (UNL)
• Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × UNL
• Haemoglobin ≥ 8 g/dL
• If a female of childbearing potential, confirmation of a negative pregnancy test before enrolment and use of double-barrier contraception, oral contraceptive plus barrier contraceptive, or confirmation of having undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation
• If a male, use of an effective barrier method of contraception during the study and for 3 months after the last dose if sexually active with a female of childbearing potential
• Ability to comply with all study-related procedures, medication use, and evaluations
• Ability to understand and give written informed consent, and comply with the protocol

Exclusion Criteria:

• Primary refractory multiple myeloma
• Previous treatment with cytotoxic chemotherapy or large-field radiotherapy or other myeloma-specific therapy within 28 days prior to the screening visit (radiation to a single site as concurrent therapy is allowed)
• Treatment with a systemic investigational agent within 28 days prior to the screening visit
• Hypercalcemia (> 2.7 mmol/L)
• Extramedullary plasmocytoma not originating from bone or plasma cell leukaemia
• Previous allogenic stem cell transplantation
• Known or suspected hypersensitivity to the excipients contained in the study drug formulation
• Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association (NYHA) classes III-IV)
• Prior therapy with other monoclonal antibodies
• Clinical or laboratory evidence of active hepatitis B (positive HBsAg with negative HBsAb) or hepatitis C (positive hepatitis c virus antibody and detectable hepatitis C virus RNA with ALT above the normal range)
• Positive HIV test result (ELISA or Western blot)
• History of ischemic colitis, stroke or myocardial infarction within the last 6 months
• Presence of diarrhoea of grade 2 or higher
• Any active uncontrolled systemic infection
• Any antibiotic therapy due to infections 2 weeks prior to first study drug administration
• Regular dose of corticosteroids during the 2 weeks prior to study entry or anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent, or any other immunosuppressive therapy within 2 weeks prior to study entry.
• Major surgery ≤ 4 weeks prior to first study drug administration or ongoing side effects of such surgery
• Systemic diseases (cardiovascular, renal, hepatic, etc) that would prevent study treatment
• Multiple myeloma with central nervous system involvement.
• Second active malignant disease, currently requiring treatment (with the exception of basal cell carcinoma of the skin or curative surgery treated tumours).
• Pregnancy or breastfeeding in women and women of childbearing potential not using an acceptable method of birth control
• others