GCS-100LE in Combination With Etoposide and Dexamethasone in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Phase 1/2 Study of GCS-100 in Combination With Etoposide and Dexamethasone in Relapsed or Refractory Diffuse Large B Cell Lymphoma

Phase 1/2, open-label, dose-escalation study to assess the safety and tolerability of GCS-100 in combination with etoposide and dexamethasone in patients with relapsed or refractory diffuse large B-cell lymphoma.

This study will investigate the safety and efficacy of the combination of GCS-100 with etoposide and dexamethasone. In vitro data demonstrates potentiation of the killing of lymphoma cells when GCS-100 is combined with dexamethasone or etoposide (Linda Baum, unpublished data; Finbarr Cotter et al, Annals of Oncology, vol 16, 205, Suppl 5.) GCS-100 will be administered in increasing doses to define a maximum tolerated dose (MTD) in combination with these chemotherapeutic agents. When the MTD is defined, the cohort will be expanded to characterize the efficacy of this combination.

Inclusion Criteria:

• Male or female patients who are 18 years of age or older with diffuse large B-cell cell lymphoma (DLBCL) relapsed or refractory after initial therapy who:

  • Are not candidates for autologous stem cell transplant.
  • Have relapsed after autologous or allogeneic stem cell transplant.
  • Have relapsed or refractory disease after 3 successive chemotherapy regimens.

• ECOG Performance Score 0-2

• Creatinine clearance > 60 mL/min/1.73 m2.

• Total bilirubin ≤2.0 X Institutional Upper Limit of Normal (IULN)

• AST (SGOT)/ALT (SGPT) ≤2.5 X IUNL, or ≤5X IUNL in patients with liver involvement of DLBCL

• Absolute neutrophil count >1,000 /_L; hemoglobin >9 g/mL; platelet count > 75,000 /_L at screening.

• Patients must be capable of understanding the purpose and risks of the study and able to provide written consent.

• Patients must be willing and able to comply with the prescribed treatment protocol and evaluations

Exclusion Criteria:

• Treatment with experimental (unlicensed) drug within 3 weeks of treatment.
• Previous chemotherapy, or major surgery within 21 days prior to first study treatment, or radiation therapy within 6 weeks.
• Rapidly progressive disease or organ function threatened by disease
• Serious, uncontrolled active infections.
• Serologically positive for HIV, HBV, or HCV.
• Clinically significant cardiac, pulmonary, and/or hepatic dysfunction
• Lymphoma involving the central nervous system
• Female patients who are pregnant or breast feeding.
• Patients not capable of understanding the purpose and risks of the study and or unable to provide written consent.
• Patients not willing and or unable to comply with the prescribed treatment protocol and evaluations