Diffuse Large B-cell Lymphoma
Conditions
Keywords
GCS-100, Diffuse Large B-cell Lymphoma, DLBCL, Relapsed or refractory DLBCL, Etoposide; Dexamethasone
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potentiation of the killing of lymphoma cells when GCS-100 is combined with dexamethasone or etoposide (Linda Baum, unpublished data; Finbarr Cotter et al, Annals of Oncology, vol 16, 205, Suppl 5.)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.
Interventions
DRUGGCS-100
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
DRUGEtoposide; Dexamethasone
Etoposide 100 mg/m2 on Study Days 3, 4 and 5; Dexamethasone 10 mg/m2 on Study Days 1, 2, 3, 4 and 5.
Sponsors
La Jolla Pharmaceutical Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Outcome results
None listed