Clinical trial NCT00776802: GCS-100LE in Combination With Etoposide and Dexamethasone in Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Official title: Phase 1/2 Study of GCS-100 in Combination With Etoposide and Dexamethasone in Relapsed or Refractory Diffuse Large B Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Keywords: GCS-100
Diffuse Large B-cell Lymphoma
DLBCL
Relapsed or refractory DLBCL
Etoposide; Dexamethasone
Lead sponsor: La Jolla Pharmaceutical Company
Sponsor class: INDUSTRY
First posted: 2008-10-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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potentiation of the killing of lymphoma cells when GCS-100 is combined with dexamethasone or etoposide (Linda Baum, unpublished data; Finbarr Cotter et al, Annals of Oncology, vol 16, 205, Suppl 5.)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

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Study Day 12 for toxicity, and 21-day cycles assessed every 2 cycles by physical and imaging assessments until disease progression
Secondary outcomes:
measure: 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
timeFrame: Baseline, Day 1, and Day 5 laboratory assessments
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
Study officials:
affiliation: UCLA, Division of Hematology/Oncology
name: Lauren Pinter-Brown, MD
role: PRINCIPAL_INVESTIGATOR
References: