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

NCT ID: NCT05330364

Last Updated: 2022-04-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2023-06-30

Brief 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.

Detailed Description

This study is aimed to observe the efficacy and safety of the Chidamide Plus Cladribine regimen in treating patients with refractory or relapsed AML. Patients must provide written informed consent and meet all the inclusion criteria and none of the exclusion criteria to be eligible. The eligible patients with refractory or relapsed AML will receive chidamide plus cladribine regimen. Response criteria will be assessed according to the guidelines of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in AML. In case of partial remission, the second identical course will be started. In case of complete remission, allogeneic hematopoietic stem cell transplantation will be performed if available. Patients without complete remission after two courses of treatment will be withdrawn from the study.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chidamide plus Cladribine

Chidamide 30mg/d per os (p.o.), twice per week, begins at day 1; Cladribine 5mg/m2/d, intravenous injection (i.v.), days 1-5, once per day; A cycle is during 28 days.

Group Type: EXPERIMENTAL

Chidamide

Intervention Type: DRUG

Chidamide 30mg/d p.o. begin at day 1, twice per week, during a 28-days cycle.

Cladribine

Intervention Type: DRUG

Cladribine 5mg/m2/d i.v. d1-5, once per day, during a 28-days cycle.

Interventions

Chidamide

Chidamide 30mg/d p.o. begin at day 1, twice per week, during a 28-days cycle.

Intervention Type: DRUG

Cladribine

Cladribine 5mg/m2/d i.v. d1-5, once per day, during a 28-days cycle.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ge Zheng

OTHER

Sponsor Role: lead

Responsible Party

Ge Zheng

Director of Department of Hematology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Zheng Ge, M.D, Ph.D

Role: STUDY_DIRECTOR

Medicine School of South East University, China

Locations

Department of Hematology, Zhongda Hospital Southeast University, Institute of Hematology Southeast University

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zheng Ge, M.D, Ph.D

Role: CONTACT

Janege879@hotmail.com

(86)025-83262468

Facility Contacts

Zheng Ge, M.D, Ph.D

Role: primary

Janege879@hotmail.com

02583262468

Other Identifiers

ZDYYGZ202103

Identifier Type: -

Identifier Source: org_study_id