A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of GS 1101 (CAL 101) in Combination with Rituximab for Patients with Previously Treated Chronic Lymphocytic Leukemia
Update: this study is closed to enrollment.
The Weill Cornell Lymphoma Program is now enrolling patients in a new clinical trial for people with previously treated Chronic Lymphocytic Leukemia (CLL). The sponsor is Gilead Sciences, and the principal investigator at Weill Cornell is Dr. Richard Furman. For more information about the study, please call Amelyn Rodriguez, RN at (212) 746-1362 or email Amelyn at firstname.lastname@example.org.
The study will evaluate the effectiveness of the experimental drug GS-1101 (CAL-101) combined with rituximab in treating CLL.
GS-1101 (CAL-101) is a pill designed to block some of the cell functions that cause CLL to grow and survive and may help control the disease. Rituximab is FDA-approved as a treatment for CLL. It is possible that giving rituximab together with GS-1101 may have more activity against the CLL disease process than giving rituximab alone.
Study participants will be randomly assigned to one of two treatment groups:
- Group A: rituximab and GS-1101
- Group B: rituximab and placebo (an inactive pill that looks like GS-1101 but contains no medicine)
All study participants will receive rituximab via infusion 8 times over 24 weeks: Day 1, then Weeks 2, 4, 6, 8, 12, 16 and 20.
Participants will take GS-1101 or placebo twice daily for 24 weeks.
After 24 weeks of therapy with rituximab and GS-1101 or placebo, participants will continue on GS-1101 or placebo as long as their CLL is controlled. If their CLL gets worse, participants may be able to take part in a separate extension study where they receive GS-1101 at a higher or lower dose. Thus, everyone who is treated in this study has an opportunity to receive active GS-1101, either in the main study or the extension study.
By Peter Martin, MD
The US Intergroup Trial E2997 was a phase 3 trial comparing two first-line chemotherapy regimens in patients with previously untreated chronic lymphocytic leukemia (CLL). A total of 278 patients were randomized to receive fludarabine (F) or fludarabine plus cyclophosphamide (FC) (click here to read the abstract). Consistent with a German CLL Study Group (GCLLSG) Trial (see abstract here), the results demonstrated that FC was associated with higher overall and complete response rate.
Importantly, neither E2997 nor the GCLLSG trial found a difference in overall survival despite the improvement in response rates. Since then, FC has been replaced by FCR (FC plus rituximab) on the basis of even better response rates demonstrated in subsequent trials. The role of cyclophosphamide in the FCR regimen, however, has been somewhat controversial. On the basis of historical comparison between trials, proponents of FCR suggest that it likely induces higher response rates than FR, especially in the group of patients deletion of the 11q (a common chromosomal abnormality in CLL cells). Other investigators point out that cyclphosphamide is a toxic chemotherapy drug that has never demonstrated an ability to improve overall survival.
Adding to this controversy is a recent publication. Dr. Mitchell Smith and colleagues re-evaluated the E2997 trial with over six-years of follow-up data and found that patients who had been randomized to the FC arm were almost twice as likely to experience a myeloid neoplasia (e.g., acute myeloid leukemia or myelodysplastic syndrome). Genetic analyses of these cancers suggested that they were associated with cyclophosphamide exposure. Importantly, the overall risk of secondary cancer in either arm was small, and the difference was not statistically significant. Nonetheless, the results certainly highlight the uncertainty regarding optimal first-line regimens.
The US Intergroup Trial CALGB 10404 is a phase 3 trial comparing FCR to FR in patients with previously untreated CLL. Update July 2013: the trial is no longer open to patient enrollment.