TEAM-Trial: Targeting Epigenetic Therapy Resistance in AML With Bortezomib
Status:
Recruiting
Trial end date:
2021-12-01
Target enrollment:
Participant gender:
Summary
The long-term outcome of patients with acute myeloid leukemia (AML) remains poor, with less
than 30% of patients achieving long lasting remission or cure. This poor outcome is largely
due to refractoriness to induction chemotherapy as well as relapses during and after
completion of intensive induction and consolidation therapy. In patients with
refractory/relapsed AML hematopoietic cell transplantation (allo-HCT) is currently the only
treatment option offering a prospect of cure but outcome is heavy influenced by the remission
status before allo-HCT. Therefore, patients are typically treated with salvage regimens based
on high dose cytarabine (HiDAC) combined with mitoxantrone, fludarabine or idarubicin.
Nevertheless, the remission rates remain poor and currently there is no accepted standard
salvage regimen. Recent studies indicate that combination chemotherapy including HiDAC and
gemtuzumab ozogamicin (GO) at a dose of 3 mg/m² leads to improved response rates in
refractory AML.
Proteasome inhibition with bortezomib appears to be a promising treatment strategy to restore
chemo-sensitivity via EZH2 stabilisation.
This study aims at improving response rates in refractory/ relapsed AML by combining high
dose cytarabine, gemtuzumab ozogamicin (GA) and bortezomib (B).
During this phase II study efficacy of B-GA is assessed in comparison to matched historical
controls using the Matched Threshold Crossing (MTC)-approach. If results are promising, a
subsequent randomized phase III study is intended to assess the efficacy of GA with or
without bortezomib.