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

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

NCT ID: NCT05906914

Condition: Acute Myeloid Leukemia, Adult

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Cladribine
Homoharringtonine

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: cladribine + homoharringtonine + cytarabine
Description: CHA Protocol: cladribine (5mg/m2, d1-3) + homoharringtonine (2mg/m2, d1-5) + cytarabine (100mg/m2 d1-7).
Arm group label: Experimental Group

Other name: Cladribine Injection

Other name: Cytarabine for injection

Other name: Homoharringtonine Injection

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not achieve a partial response, or the second course of treatment did not achieve a complete response, the patient was withdrawn from the clinical study.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.

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: 59 Years

Healthy volunteers: No

Locations:

Facility:
Name: The First Affiliated Hospital, Zhejiang University School of Medicine

Address:
City: Hangzhou
Zip: 310003
Country: China

Status: Recruiting

Contact:
Last name: Jie Sun, MD, Ph.D

Phone: +86 153 0571 4109
Email: jsun1492@zju.edu.cn

Start date: June 29, 2023

Completion date: June 30, 2025

Lead sponsor:
Agency: First Affiliated Hospital of Zhejiang University
Agency class: Other

Source: First Affiliated Hospital of Zhejiang University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05906914