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

Study Overview
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Brief Summary
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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
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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potentiation of the killing of lymphoma cells when GCS-100 is combined with dexamethasone or etoposide (Linda Baum, unpublished data; Finbarr Cotter et al, Annals of Oncology, vol 16, 205, Suppl 5.)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.

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

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: GCS-100
* Drug: Etoposide; Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GCS-10<br> | Drug: GCS-100<br>* GCS-100 80 mg/m2 IV (in the vein) on Study Days 1, 2, 3, 4, and 5 of a 21-day course. Three or up to six patients will be enrolled in each cohort until the maximum tolerated dose is reached. The dose levels: 1) 80 mg/m2; 2) 120 mg/m2; 3) 160 mg/m2<br>Drug: Etoposide; Dexamethasone<br>* Etoposide 100 mg/m2 on Study Days 3, 4 and 5; Dexamethasone 10 mg/m2 on Study Days 1, 2, 3, 4 and 5.<br>* Other names: Decadron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Day 12 for toxicity, and 21-day cycles assessed every 2 cycles by physical and imaging assessments until disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GCS-100, Diffuse Large B-cell Lymphoma, DLBCL, Relapsed or refractory DLBCL, Etoposide; Dexamethasone