Safety and Efficacy Study of TNX-650 to Treat Refractory Hodgkin's Lymphoma

The purpose of this study is to determine the safety and effectiveness of TNX-650 for Injection when administered to patients with refractory Hodgkin's lymphoma.

Hodgkin's lymphoma (HL) is a lymphoid malignancy that accounts for approximately 7,000 to 8,000 new cancer cases per year in the United Sates. It occurs with a bimodal age-incidence distribution peaking in the 15- to 30-year old and 50- to 60-year old age groups. The pathological hallmark of the disease is the presence of malignant Reed Sternberg (RS) cells. Reed-Sternberg cells are interspersed among a heterogeneous population of non-malignant reactive cells, including T cells, eosinophils, neutrophils, B lymphocytes, plasma cells, histiocytes, fibroblasts, and stromal cells.

While more than 80% of patients will respond to initial radiotherapy or combination chemoradiotherapy, some patients will experience early relapse after initial therapy or be refractory to first-line therapy. These patients may be treated with second-line therapy, which may include autologous bone marrow transplantation (BMT). Patients with HL who relapse after first- and second-line therapy, or who are refractory to therapy, with or without autologous BMT, have a poor prognosis. The long-term event-free survival rate in this patient group is less than 10%; median survival is 16 months. At present, these patients have no treatment options other than investigational therapies.

Eligibility Criteria:
Inclusion Criteria:

* Histological diagnosis of relapsed or refractory classical HL
* Age \>18 years
* Received and failed potentially curative chemotherapeutic regimens (e.g., ABVD, Stanford V, or BEACOPP)
* Relapsed following autologous bone marrow transplantation (BMT), or are ineligible, or refused BMT
* Completed radiotherapy, chemotherapy, and/or treatment with other investigational agents at least 3 weeks prior to study entry
* Completed autologous BMT (if received) at least 3 months prior to study entry; completed allogeneic BMT (if received); at least 6 months prior to study entry
* Eastern Cooperative Oncology Group (ECOG) status of \<2
* Life expectancy of \>3 months
* Laboratory data:

  * Platelet count \>50,000/mm3
  * Hemoglobin \>9.0 g/dL (may be maintained by transfusion)
  * Absolute neutrophil count \>1000/mm3
  * ALT/AST \<2.5 times the upper limit of normal (ULN)
  * Total bilirubin \<1.5 times ULN
  * Creatinine \<1.5 mg/dL
* Female subjects of childbearing potential must have a negative serum pregnancy test at screening; subjects must agree to use a medically appropriate form of birth control from screening until 6 months after the last dose of study medication
* Ability to provide written informed consent

Exclusion Criteria:

* Any significant diseases (other than HL) or clinically significant findings, including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the subject from participating in the study
* History or clinical evidence of cnetral nervous system (CNS) HL
* Received allogeneic BMT
* Received growth factor support or transfusions to achieve hematology entry criteria (platelets, hemoglobin, absolute neutrophil count)
* Major surgery within 4 weeks prior to study entry
* Known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation
* Known history of another primary malignancy that has not been in remission for at least 5 years. Non-melanoma skin cancer and cervical carcinoma in situ or squamous intraepithelial lesions (e.g., cervical intraepithelial neoplasia \[CIN\] or prostatic intraepithelial/intraductal neoplasia \[PIN\]) are allowed.
* Any active viral, bacterial, or systemic fungal infection within 4 weeks prior study entry
* Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV)
* Histry of significant chronic or recurrent infections requiring treatment
* Receiving systemic steroids exceeding 10 mg prednisone or equivalent, or unstable on steroid medication, during the 3 weeks immediately preceding enrollment
* Pregnant or breast-feeding