Clinical Study Protocol of Maintenance Therapy With Venetoclax in Elderly Patients With AML in First Complete Remission

Official title

Clinical Study Protocol of Maintenance Therapy With Venetoclax in Elderly Patients With Acute Myeloid Leukemia (AML) in First Complete Remission

Overview

This clinical study evaluates the efficacy and safety of maintenance therapy with BCL-2 inhibitors in elderly patients with acute myeloid leukemia (AML) in first complete remission. This study involves the following content: BCL-2 inhibitors.

Detailed description

This is a prospective, multicenter, open-label, single-arm clinical study that aims to observe the efficacy and safety of maintenance therapy with BCL-2 inhibitors in elderly patients with acute myeloid leukemia (AML) in first complete remission.

The FDA has approved the combination therapy of Venetoclax and Decitabine/Azacitidine for elderly (\>60 years old) newly diagnosed AML patients who are not eligible for intensive chemotherapy. Venetoclax, the first highly selective BCL-2 inhibitor available globally, is a BH3 mimetic that selectively binds to the BCL-2 protein, displacing and releasing pro-apoptotic proteins that were originally bound to BCL-2, effectively inducing apoptosis in tumor cells.

In recent years, maintenance therapy for elderly AML patients has also been under continuous exploration. In 2020, Andrew et al. published clinical trial results in the New England Journal of Medicine, demonstrating the use of oral Azacitidine formulation (CC-486) as maintenance therapy for elderly AML patients who achieved their first complete remission (CR1).

Considering the high response rate achieved by BCL-2 inhibitors in treating elderly AML and the tolerable adverse effects, maintenance therapy has shown survival benefits and good safety profiles in elderly AML patients. Therefore, your plan is to further explore, refine, and optimize treatment strategies for elderly AML patients by administering BCL-2 inhibitor maintenance therapy to those who have achieved their first CR, evaluating patient overall survival (OS), relapse-free survival (RFS), and treatment safety through a comparative study with a control group. This aims to preliminarily establish the role of this maintenance regimen in the treatment of elderly AML.

Participants will be recruited within 24 months from the completion of consolidation therapy, and the BCL-2 inhibitor maintenance therapy will last for 12 cycles, with each cycle consisting of 28 days. The analysis will be conducted approximately 48 months after the enrollment of the first patient and the follow-up will continue for 2 years from the randomization of the last patient.

Specific protocol:

During the consolidation phase, which occurs within 2 months after the completion of consolidation therapy, the BCL-2 inhibitor maintenance treatment will consist of 12 cycles, with each cycle lasting 28 days.

The specific regimen for the BCL-2 inhibitor is as follows:

BCL-2 inhibitor: 400mg/day, orally, from day 1 to day 14 of each cycle.

The target is to enroll 100 eligible patients.

Interventions

• Drug Venclexta 100 MG Oral Tablet
  When there is a deficiency of neutrophils, G-CSF treatment may be necessary. The treatment is continued until the absolute neutrophil count (ANC) reaches either \>0.5×109/L and remains at that level for 3 consecutive days, or \>2×109/L. The purpose of G-CSF therapy in this context is to stimulate the production of neutrophils and restore their levels to a sufficient and stable range. This helps to strengthen the immune system and reduce the risk of infections associated with low neutrophil count

Primary outcome measures

• 2-year overall survival (OS) [Time frame: From the time of CR/CRi to time for up to 2 years]
• Recurrence-free survival (RFS) [Time frame: From the time of CR/CRi to time for up to 2 years]

Secondary outcome measures (3)

• Assessment of efficacy. [Time frame: At the end of the 6 cycle of treatment, which corresponds to 28 days per cycle.]
• The impact of maintenance therapy on minimal residual disease (MRD) kinetics. [Time frame: From the time of CR/CRi to time for up to 2 years]
• Safety evaluation [Time frame: From the time of CR/CRi to time for up to 2 years]

Eligibility criteria

Inclusion criteria

• Patients with acute myeloid leukemia (AML) diagnosed based on bone marrow morphology and immunophenotyping (meeting the diagnostic criteria of WHO 2016).
• Achieving first complete remission (CR) or incomplete complete remission (CRi) after 1-2 cycles of induction therapy and receiving consolidation treatment for at least 4 cycles.
• Age between 60 and 85 years.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3 times the upper limit of normal (ULN), serum bilirubin ≤ 1.5 times ULN, serum creatinine ≤ 2.0 times ULN, and serum creatine kinase < 2.0 times ULN.
• Left ventricular ejection fraction (LVEF) ≥ 50% as determined by echocardiography.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. Obtaining informed consent from the patient or their legal representative.

Exclusion criteria

• Acute promyelocytic leukemia, myeloid sarcoma, blast phase of chronic myeloid leukemia.
• Patients who achieve CR after relapse and re-induction therapy.
• Extramedullary involvement of AML, including active central nervous system leukemia.
• Allergy to any of the drugs involved in the protocol. Pregnant or lactating women and reproductive-age patients who are unwilling to use contraception.
• Significant abnormalities in liver or kidney function beyond the inclusion criteria.
• Presence of organic heart disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction with clinical symptoms or cardiac dysfunction within the past 6 months (according to New York Heart Association functional classification NYHA ≥ 3).
• Concurrent presence of other malignant tumors, except for the following conditions:

• Patients who have received curative-intent treatment and have not had any known active disease of malignant tumors for ≥ 5 years before enrollment.
• Patients who have received adequate treatment and do not show signs of disease for non-melanoma skin cancer or malignant melanocytic nevi (even if it is within 3 years before randomization).
• Patients who have received adequate treatment and do not show signs of disease for in situ carcinoma (even if it is within 3 years before randomization).
• Patients with HIV/AIDS, syphilis, active hepatitis B (detectable HBV-DNA), and hepatitis C.
• Any concurrent medical condition or disease (such as active systemic infection) that may interfere with the study procedures or results or pose risks to the participant as determined by the investigator.Inability to understand or comply with the study protocol.
• Patients younger than 60 years or older than 85 years.
• Undergoing major surgery within 4 weeks prior to randomization.
• Patients who have undergone allogeneic hematopoietic stem cell transplantation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital with Nanjing Medical University — Nanjing

Identifiers

NCT: NCT05909293 · 2022-SR-541

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗