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

NCT05330364 | Unknown Phase 2

• 1 other identifier: ZDYYGZ202103
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Chidamide; Cladribine

Outcome Measures

Primary Outcomes (1)

• Complete Remission (CR) rate

  Less than 5 percent of blast cells in bone marrow aspiration is defined as CR.

  Bone marrow examination will be performed at the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (2)

• Incidences of Adverse Events (AEs)

  All AEs reported from the time of study drug administration until 30 days after discontinuation of study drug administration will be collected.

• Overall Survival (OS)

  OS is defined as the number of days from the date of the study enrollment to the date of death of any cause with a minimal 12 months of follow up. Subjects that have not died will be censored at the last known date to be alive.

Study Arms (1)

Chidamide plus Cladribine

EXPERIMENTAL

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.

Drug: Chidamide; Drug: Cladribine

Interventions

Chidamide DRUG

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

Chidamide plus Cladribine

Cladribine DRUG

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

Chidamide plus Cladribine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ge Zheng: lead

Study Sites (1)

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

Nanjing, Jiangsu, 210009, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; Cladribine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Zheng Ge, M.D, Ph.D

  Medicine School of South East University, China

  STUDY DIRECTOR

Central Study Contacts

Zheng Ge, M.D, Ph.D

CONTACT

(86)025-83262468; Janege879@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Department of Hematology

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: April 15, 2022
• Study Start: June 1, 2021
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: April 29, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)