Study of Chidamide Combined With Cladribine in Refractory/Relapsed Acute Myeloid Leukemia

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ge Zheng
• Treatments: Cladribine

Criteria

Inclusion Criteria:

• Age greater than 18 years old and less than 75 years old;

• Clinical diagnosis of Relapsed/Refractory AML (non-APL);

• ECOG performance status score 0-3;

• Participant has the ability to understand and willingness to sign a written consent document.

Exclusion Criteria:

• Pregnancy or nursing

• Uncontrolled significant cardiac disorder

• Psychiatric disorder may interfere with his / her compliance with the study protocol

• Known history of intolerance or allergy to any component of the research regimen

• Any condition not suitable for the trial as judged by the study investigator.