Study of Chidamide Combined With Cladribine in Refractory/Relapsed Acute Myeloid Leukemia
Status:
Recruiting
Trial end date:
2023-06-01
Target enrollment:
Participant gender:
Summary
Acute myeloid leukemia (AML) is highly heterogeneous, the efficacy of the individual varies
greatly, and the risk of recurrence is high. A large number of newly diagnosed AML patients
cannot achieve complete remission (CR) after standard induction chemotherapy. The prognosis
of AML patients after relapse is extremely poor, and only a few patients can get remission
through salvage treatment.
Chidamide is a histone deacetylase inhibitor (HDACi) independently developed by China. It has
been marketed in recent years and the first innovative drug approved by the U.S. Food and
Drug Administration for clinical research in the United States. Chidamide can increase the
sensitivity of leukemia cells to conventional chemotherapy by inhibiting cell proliferation,
inducing apoptosis, and increasing cell cycle arrest. Chidamide and other drugs have
different effects in combination, and jointly bear the anti-tumor effect, which provides a
theoretical basis for Chidamide in the treatment of acute myeloid leukemia.
Cladribine is a purine nucleoside analog, which has the ability to inhibit DNA synthesis,
repair, induce apoptosis, and has anti-leukemia activity for cells in both mitotic and
quiescent phases. In the past ten years, many studies have proved that Cladribine and its
combination therapy are effective in patients with relapsed and refractory AML and de novo
AML. The NCCN guidelines recommend the combination of cladribine as a category 1
recommendation for newly-diagnosed and refractory or relapsed adult AML. Several studies have
confirmed the use of Cladribine in the treatment of refractory and relapsed AML.
The strong synergistic anti-cancer effect of HDACi combined with Cladribine has been shown in
many cancers such as B-cell chronic lymphocytic leukemia, colon cancer, multiple myeloma,
natural killer large granular lymphocytic leukemia, B-cell non-Hodgkin's lymphoma, and mantle
cell lymphoma. Our previous study found a synergistic effect on combination of Chidamide and
Cladribine in AML cell lines and primary cells. In clinical observation, refractory and
relapsed AML patients also responded well to the combination of Chidamide plus Cladribine
regimen. This provides a theoretical and practical basis for the use of the combination of
Chidamide and Cladribine in AML patients.