Cladribine Plus Homoharringtonine and Cytarabine Regimen (CHA) for de Novo Acute Myeloid Leukemia

NCT ID: NCT05906914

Last Updated: 2025-05-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-26
• Study Completion Date: 2025-12-31

Brief Summary

The goal of this clinical trial is to evaluate the response and safety of Cladribine plus Homoharringtonine and Cytarabine regimen (CHA) protocol in de novo acute myeloid leukemia with age <60y. This is a prospective, single-armed mono-center based investigator-initiated trial. About 30 patients who meet the enrollment criteria with be treated with CHA as induction chemotherapy. The complete response rate, survival rate, recurrence rate, and treatment-related mortality with be observed.

Detailed Description

In this study, a new chemotherapy regimen named CHA which composed of cladribine, homoharringtonine and cytarabine, was proposed for the induced remission treatment of adult acute myeloid leukemia, and the efficacy and safety of this regimen were evaluated. Enrolled patients will receive cladribine (5mg/m2, d1-3) + homoharringtonine (2mg/m2, d1-5) + cytarabine (100mg/m2, d1-7). If more than partial remission is achieved in the first course, a course of CHA regimen is repeated. If the first course of treatment did not achieve a partial response, or the second course of treatment did not achieve a complete response, the patient was withdrawn from the clinical study. Transplantation was stratification according to the prognostic risk stratification. Patients with favourable risk received 3 cycles of high-dose intravenous cytarabine (1-3g/m2, Q12H d1-3). Or 3 cycles of medium dose cytarabine (1.0g/m2, Q12H d1-3) combined with idarubicin (10mg/m2, d1-3) or etoposide (100mg, d1-3). Patients with intermediate risk who achieve minimal residual disease (MRD) negative in the first or second cycle can receive high-dose or intermediate-dose cytarabine chemotherapy, otherwise allogeneic hematopoietic stem cell transplantation (HSCT) is recommended. Patients with high risk are advised to receive allogeneic HSCT, or receive high-dose or intermediate-dose cytarabine.Bone marrow samples were collected at enrollment for bone marrow cytology, flow cytometry and next-generation sequencing. The probes for targeted sequencing covered exons and selected introns of 88 myeloid leukaemia-related genes for next-generation sequencing. Bone marrow was collected on day 28 after each treatment cycle, including bone marrow cytology and measurable residual disease (MRD) assessments, for response assessment.The response assessment was evaluated according to the Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. The primary study endpoint was the composite complete remission (CR) rate (CR and CR with incomplete hematology recovery, CRi), assessed in all treated populations according to the Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. The secondary endpoints were minimal residual disease in bone marrow measured by flow cytometry after one cycle of induction therapy, as well as overall survival (OS), event-free survival, and adverse events, assessed in all treated populations.

Conditions

Acute Myeloid Leukemia, Adult

Study Design

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

Study Groups

Experimental Group

Intervention: CHA

Group Type: EXPERIMENTAL

cladribine + homoharringtonine + cytarabine

Intervention Type: DRUG

CHA Protocol: cladribine (5mg/m2, d1-3) + homoharringtonine (2mg/m2, d1-5) + cytarabine (100mg/m2 d1-7).

Interventions

cladribine + homoharringtonine + cytarabine

CHA Protocol: cladribine (5mg/m2, d1-3) + homoharringtonine (2mg/m2, d1-5) + cytarabine (100mg/m2 d1-7).

Intervention Type: DRUG

Other Intervention Names

Cladribine Injection; Cytarabine for injection; Homoharringtonine Injection

Eligibility Criteria

Inclusion Criteria

1. The age is 18 to 59 years old, gender is not limited, race is not limited.

2. Diagnosed as acute myeloid leukemia (AML) according to the diagnostic criteria of the World Health Organization (WHO) in 2016.

3. No previous anti-acute leukemia therapy (including demethylation drugs for leukemia or myelodysplastic syndrome (MDS), except hydroxyurea and leukocytosis).

4. Physical status <= 2 according to eastern tumor cooperation group (ECOG).

5. Within 21 days before random grouping and at baseline, biochemical indicators must be within the following limits: Glutamic pyruvic transaminase (ALT) and glutamic oxaloacetic transaminase (AST) <= 3 × normal upper limit (ULN); total bilirubin <= 3 × ULN; serum creatinine <= 2 × ULN or serum creatinine clearance rate (CrCl)>= 40mL/min.

6. The left ventricular ejection fraction| (LVEF) measured by echocardiography was in the normal range (LVEF > 50%).

7. Each patient (or his or her legal representative) must sign an informed consent form (ICF), indicating that he / she understands the purpose and procedures of the study and is willing to participate in the study.

Exclusion Criteria

1. Diagnosed or receiving treatment for other malignant tumors other than AML that are or are in need of treatment in the near future.

2. Acute promyelocytic leukemia, myeloid sarcomas, accelerated and acute transformation of chronic myeloid leukemia.

3. Patients with severe liver and kidney function, cardiopulmonary insufficiency.

4. Uncontrolled or severe infection.

5. Mental illness that may prevent subjects from completing treatment or informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jie Sun

Role: PRINCIPAL_INVESTIGATOR

Zhejiang University

Locations

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhen Cai, MD, Ph.D

Role: CONTACT

caiz@zju.edu.cn

+86 138 5719 0311

Facility Contacts

Jie Sun, MD, Ph.D

Role: primary

jsun1492@zju.edu.cn

+86 153 0571 4109

Other Identifiers

IIT20220027C-R2

Identifier Type: -

Identifier Source: org_study_id