Phase I/II Study of hLL1 in Multiple Myeloma

A Phase I/II Study of Immunotherapy With hLL1 Administered Twice Weekly for 4 Consecutive Weeks in Patients With Multiple Myeloma

This is a Phase I/II, open-label, multi-center study conducted in patients with recurrent or refractory multiple myeloma who have failed at least two prior standard systemic treatments.

All patients receive hLL1 administered intravenously twice weekly for 4 consecutive weeks. Cohorts of 3-6 patients will receive escalating doses of hLL1 in order to determine the maximum tolerated dose (MTD) for this administration schedule. Up to approximately 30 additional patients will be entered at one or more dose levels at or below the MTD in order to determine the optimal dose for subsequent studies.

Inclusion Criteria:

• Able to provide signed, informed consent;
• Male or female, >/=18 years old;
• Meets clinical trial criteria for a diagnosis of multiple myeloma (Appendix 1)
• Stage II or III at study entry by Durie-Salmon staging, with either renal function subclassification (A or B) allowed (Appendix 2).
• Secretory multiple myeloma one or more criteria for measurable disease (serum M protein >1.0 gm/dl measured by serum protein electrophoresis, serum free light chain measurement >200 mg/dl, urinary M protein excretion >200 mg/24 hours);
• Refractory or relapsed to at least two prior standard systemic anti-myeloma treatment regimens;
• Adequate performance status (Karnofsky Scale >/= 60%);
• Life expectancy at least 6 months;
• Adequate hematologic status within 2 weeks before study drug administration:
• Hemoglobin >8.0 g/dL and platelets > 50,000/mm3 (both without transfusion or other hematologic support within 7 days of laboratory testing)
• White blood count (WBC) > 2,000/mm3and absolute neutrophil count (ANC) >1,000/mm3 (both without the use of colony stimulating factors within 7 days of laboratory testing)
• Adequate renal function: serum creatinine < 1.5 x the upper limit of normal (ULN);
• Adequate hepatic function AST or ALT < 2.5 x the ULN; Total bilirubin < 1.5 x the ULN

Exclusion Criteria:

• Pregnant or lactating women.
• Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study until at least 12 weeks after the last hLL1 infusion;
• Prior chemotherapy, immunotherapy, radiotherapy, plasmapheresis, kyphoplasty, or major surgery within 4 weeks; prior stem cell transplant within 12 weeks; prior treatment with rituximab within 6 months. Must have recovered from all toxicity from prior treatments;
• Prior therapy with other murine, chimeric, human or humanized monoclonal antibodies, unless HAHA tested and negative;
• Prior treatment with any investigational agents within 3 months, unless completed follow-up, off study, and agreed by Sponsor;
• Prior malignancy within 5 years, excluding multiple myeloma, non-melanoma skins cancers and cervical carcinoma in situ;
• Known to be HIV positive, or hepatitis B or C positive;
• Known autoimmune disease or presence of autoimmune phenomena;
• Systemic infection or requiring anti-infectives within 7 days before first dose of study drug;
• Substance abuse or other concurrent medical conditions that, in the investigator's opinion, could confound study interpretation or affect the patient's ability to tolerate or complete the study.