Study of SGN-40 in Patients With Refractory or Recurrent Multiple Myeloma

This is an open-label, multi-dose, single-arm, phase I, dose-escalation study to define the toxicity profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of SGN-40 in patients with refractory or recurrent multiple myeloma.

A minimum of three patients will be entered into each dose-level cohort. All patients will receive a dose-loading schedule during the first two weeks. The maximum weekly dose will be 16mg/kg.

Inclusion criteria

• Patients must have refractory or recurrent secretory multiple myeloma (MM).
• Patients must have failed at least two different prior systemic therapies for MM.
• Patients may have received a maximum of five cytotoxic regimens.
• Patients who have received any of the following must complete within the specified time frame below:

• Autologous stem cell transplant - 12 weeks prior to first dose
• Nitrogen Mustard agents, Melphalan, BCNU, IVIG, or monoclonal antibody therapy - 6 weeks prior to first dose
• Chemotherapy, Radiation, or other therapies for MM - 4 weeks prior to first dose
• Patients who have not undergone autologous stem cell transplantation must be either ineligible for stem cell transplantation or, if eligible, must have refused treatment by autologous stem cell transplantation.
• Patients must have an ECOG performance status of ≤ 2 and a life expectancy > three months.
• Patients must be available for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution for the entire duration of the study.
• Patients must be at least 18 years of age.
• Females of childbearing potential must have a negative β-HCG pregnancy test result within three days of enrollment. All patients must plan to use an effective contraceptive method during the course of the study.
• Patients must meet baseline lab data requirements.
• Patients must give written informed consent.

Exclusion criteria

• Patients with non-secretory MM or solitary plasmacytoma or plasma cell leukemia.
• Patients with a history of allogeneic transplantation.
• Patients receiving plasmapheresis within four weeks prior to enrollment.
• Patients undergoing major surgery within four weeks prior to enrollment.
• Patients with a known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation.
• Patients with a history of other malignancies during the past five years with the exception of adequately treated basal or squamous cell skin cancer or cervical carcinoma in situ.
• Patients with any active viral, bacterial, or systemic fungal infection within four weeks of enrollment.
• Patients with a history of significant chronic or recurrent infections requiring treatment.
• Patients with a history of active thrombosis within three months of enrollment.
• Patients with a history of pulmonary embolism.
• Patients with a history of migraines or severe headaches requiring medical therapy within 12 months of enrollment.
• Patients who are pregnant or breastfeeding.
• Patients with uncontrolled hypercalcemia.
• Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment.
• Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent.