GVAX Immunotherapy for Leukemia
GVAX immunotherapy for leukemia is a non patient-specific investigational product being evaluated in investigator-sponsored Phase 2 clinical trials in individuals with newly diagnosed acute myelogenous leukemia (AML) as well as in individuals with chronic myelogenous leukemia (CML) and myelodysplastic syndrome (MDS). The goal of GVAX immunotherapy in both AML and CML is to reduce or eliminate the potential for minimal residual disease, which frequently occurs following treatment with the current standard of care.
| AML | GVAX immunotherapy for leukemia administered following initial chemotherapy and pre- and post-hematopoietic stem cell transplantation. |
| CML | GVAX immunotherapy for leukemia administered following treatment with Gleevec® (imatinib mesylate) for more than one year. |
| MDS | GVAX immunotherapy for leukemia administered as a single agent. |
GVAX immunotherapy for leukemia is comprised of whole cells derived from a single leukemia cell line. As with all GVAX® cancer immunotherapies, the cells are modified to secrete GM-CSF, an immune stimulatory cytokine, and irradiated to arrest growth while still allowing the cells to remain metabolically active to secrete GM-CSF.
This program is being conducted in collaboration with researchers at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.
Encouraging Phase 2 Data
Over the past years, researchers have presented encouraging data from Phase 2 clinical trials of GVAX immunotherapy for leukemia in patients with AML and CML. The most recently reported results are summarized below.
Acute myelogenous leukemia
In May 2005, updated data from a Phase 2 clinical trial GVAX immunotherapy for leukemia used in combination with autologous leukemia cells in patients with AML were presented at the annual meeting of the American Society of Clinical Oncology (ASCO). Preliminary findings of this trial, which enrolled 54 patients, indicated that GVAX immunotherapy is generally well tolerated and may reduce residual leukemic cells that persist after chemotherapy, as indicated by decreased levels of WT-1, a leukemia-associated genetic marker that is detectable in over 95 percent of patients with active AML. Eleven of 16 patients tested to date were reported to have decreased WT-1 levels in their peripheral blood following the initiation of GVAX immunotherapy. Furthermore, two-year relapse-free survival after a single pre-transplant immunotherapy was greater in these 11 patients compared to those that did not have decreases in WT-1 (73% v. 0%, p=0.03).
Chronic myelogenous leukemia
In June 2006, preliminary findings from an investigator-sponoserd Phase 2 clinical trial of GVAX immunotherapy for leukemia in patients with CML were presented at the annual meeting of ASCO. In this trial, 19 CML patients with molecular evidence of persistent leukemia following at least one year of Gleevec therapy were treated with GVAX cancer immunotherapy for leukemia while continuing to receive Gleevec.
Interim findings indicated that the addition of GVAX immunotherapy for leukemia to Gleevec therapy reduced persistent leukemic disease in 10 of 19 patients as demonstrated by a complete disappearance of, or a greater than one log reduction in bcr-abl, a validated genetic marker found on the leukemic cells. Five of these 10 patients demonstrated a complete disappearance of bcr-abl, and the additional five patients demonstrated a greater than one log (90 percent) reduction in bcr-abl. Reductions of bcr-abl have been previously shown to be strongly associated with improved progression-free survival in CML patients treated with Gleevec. The responses were ongoing in all but one of the remaining 10 responders, with a median follow-up from treatment of 14 months. Of the remaining nine patients, only one patient has developed cytogenetic progression on therapy. Administration of GVAX immunotherapy for leukemia was generally well tolerated.
clinical trials under way
Three clinical trials GVAX immunotherapy for leukemia are currently under way in collaboration with researchers at the Johns Hopkins Sidney Kimmel Cancer Center:
- Phase 2 clinical trial of GVAX immunotherapy for leukemia (CML) used in combination with continued Gleevec treatment versus the combination of interferon-alpha, GM-CSF plus continued Gleevec treatment.
- Open for Enrollment (www.clinicaltrials.gov, NCT00363649) - Phase 1 clinical trial of GVAX immunotherapy for leukemia in patients with MDS
- Open for Enrollment (www.clinicaltrials.gov, NCT00361296) - Extension study of the initial Phase 2 clinical trial of GVAX immunotherapy for leukemia (CML) used in combination with Gleevec