AML Trial Halted Due to COVID-19 Pandemic
March 30, 2020 09:08pm
By Lisa Astor
The autologous dendric cell vaccine targeting Wilms tumor-1 antigens with or without preferentially Expressed Antigen in Melanoma was well tolerated and feasible in patients with acute myeloid leukemia, meeting the co-primary end points of the phase I/II clinical trial.
The autologous dendric cell (DC) vaccine targeting Wilms tumor-1 (WT1) antigens with or without preferentially Expressed Antigen in Melanoma (PRAME) was well tolerated and feasible in patients with acute myeloid leukemia (AML), meeting the co-primary end points of the phase I/II clinical trial (NCT02405338), according to a press release from Medigene AG, developer of the agent.1
The co-primary end points of the study included the feasibility and safety of the vaccine after 2 years. The DC vaccine did not lead to any serious treatment-related adverse events. Secondary end points included overall survival (OS) and progression-free survival (PFS). After 24 months of treatment, the OS was 80% (95% CI, 55%-92%), and the PFS rate was 55% (95% CI, 31%-74%).
“New treatment options are desperately needed for patients with AML. The disease progresses rapidly and may be fatal within a few weeks or months, if untreated,” Yngvar Floisand, head physician of the Department of Hematology at the Oslo University Hospital and principal investigator of the trial, said in a statement. “Even despite having received a treatment, the majority of predominantly elderly patients continue to experience minimal residual disease burden that sooner or later leads to relapse of the disease. Medigene’s DC vaccine trial was designed towards potentially making new treatments available for these patients, specifically aiming at reducing the risk of relapse in treated patients after completing conventional chemotherapy.”
Half of the patients in this trial are 60 years or older. This subgroup of elderly patients is generally ineligible for hematopoietic stem cell transplant (SCT) and associated with poorer outcomes. Patients below the age of 60 years were categorized into risk groups of good (n = 9), intermediate (n = 1), and poor (n = 0). These patients had an OS of 80% (95% CI, 41%-95%) and a PFS rate of 60% (95% CI, 25%-83%) at 24 months.
According to interim findings at the 2019 American Society of Hematology (ASH) Annual Meeting, 12 out of 20 patients remained in remission during the first year of treatment, while 8 patients relapsed. Most cases of relapse on the trial occurred within the initial 80 days of treatment (5 out of 8).1A molecular mutational analysis suggested some relapses began prior to the start of the study drug. Two patients died out of the 8 total who relapsed during the first year.2
Investigators also evaluated WT1- and PRAME-specific T cell responses in the peripheral blood (IFN- γ ELISPOT) and recurrence of WT1- and/or PRAME-positive AML blasts in the bone marrow and peripheral blood. Seven out of the 12 patients in remission had no detectable IFN-γ ELISPOT response in the peripheral blood, while 3 of the 12 patients had a response, and 2 were not evaluable because of high background production of IFN-γ. The 3 IFN-γ ELISPOT responses occurred within the first 30 weeks of treatment. These responses were associated with a decrease in levels of WT1 in all 3 patients and a decrease in levels of PRAME in 1 patient.
In the multicenter, open-label, prospective phase I/II trial, 20 patients with AML who are in remission received the autologous WT1/PRAME DC vaccine by intradermal injection once a week for the first 4 weeks, followed by once per month for 23 consecutive months. Patients were treated until 2 years, progression of disease, or study withdrawal. Diagnoses were established at a median of 9.8 months prior to the first vaccination (range, 4.5-17.5 months), and the last chemotherapy infusion happened at a median of 6.9 months (range, 2-14.8 months).
To be eligible for the trial, patients had to have a complete remission (CR) with or without hematologic recovery (Cri) following induction chemotherapy and express WT1 protein with or without PRAME positivity. Patients were ineligible if they were suitable for allogenic SCT, were not in CR or Cri with bone marrow blast count of 5% or greater, or had concurrent active second malignancies other than non-melanoma skin cancers.
DCs are a type of immune cells which process antigens and present short peptides to the cell surface. The peptides become activated when recognized by T cells or natural killer cells. These activated immune cells are then able to eliminate tumor cells in the cancer. Medigene focused on the development of T cell-receptor modified T cells.
“The now final top-line results from this phase I/II clinical trial with patient-derived DCs confirm the previously published promising 12-months interim analysis. The clinical outcome is encouraging, not only regarding the excellent safety and tolerability profile but also for overall survival when it comes to secondary endpoints,” Floisand stated.
Positive Final 2-Year Topline Data in Completed DC Vaccine Phase I/II Trial in AML Patients [news release]. Martinsried and Munich, Germany: Medigene AG; January 10, 2020. https://bit.ly/2suMjkV. Accessed January 16, 2020.