Phase 1/2 Study of GCS-100 in Combination With Etoposide and Dexamethasone in Relapsed or Refractory Diffuse Large B Cell Lymphoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Locations
- 1
- Primary Endpoint
- To determine the maximum tolerated dose of GCS-100 in combination with etoposide and dexamethasone by comprehensive lab, pharmacokinetics, physical assessments, and PET-CT imaging.
Study Overview
Brief Summary
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.
Detailed Description
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potentiation of the killing of lymphoma cells when GCS-100 is combined with dexamethasone or etoposide (Linda Baum, unpublished data; Finbarr Cotter et al, Annals of Oncology, vol 16, 205, Suppl 5.)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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 m
- •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
Arms & Interventions
GCS-10
Intervention: GCS-100 (Drug)
GCS-10
Intervention: Etoposide; Dexamethasone (Drug)
Outcomes
Primary Outcomes
To determine the maximum tolerated dose of GCS-100 in combination with etoposide and dexamethasone by comprehensive lab, pharmacokinetics, physical assessments, and PET-CT imaging.
Time Frame: Study Day 12 for toxicity, and 21-day cycles assessed every 2 cycles by physical and imaging assessments until disease progression
Secondary Outcomes
- Overall response rate; correlate response to GCS-100 with the expression of galectin-3 in tumors; correlate serum galectin-3 levels with the administration of GCS-100(Baseline, Day 1, and Day 5 laboratory assessments)