A Bridging Study of Liposomal Cytarabine-Daunorubicin in Treating Olderly Patients With Treatment-naive High-Risk (Secondary) Acute Myeloid Leukemia

NCT06182592 | Not Yet Recruiting Phase 3

• 1 other identifier: HC1702-004
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this bridging study is to determine the efficacy of liposomal cytarabine-daunorubicin for injection compared with cytarabine and daunorubicin in older patients with high-risk (secondary) acute myeloid leukemia.

Conditions

High-risk (Secondary) Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall survival will be measured from the date of randomization to death from any cause.

  Up to 2 years

Secondary Outcomes (6)

• Event-free survival (EFS)

  Up to 2 years

• Duration of remission (DoR)

  Up to 2 years

• CR rate

  Up to 2 years

• Composite remission rate

  Up to 2 years

• Proportion of patients receiving a haematopoietic stem cell transplant (HSCT)

  Up to 2 years

Study Arms (2)

Arm A (liposomal cytarabine-daunorubicin for injection)

EXPERIMENTAL

Patients are eligible to receive up to 2 inductions and up to 2 consolidations with liposomal cytarabine-daunorubicin for injection. The number of inductions and consolidations a patient received will depend on response.

Drug: Liposomal cytarabine-daunorubicin for injection

Arm B (7+3)

EXPERIMENTAL

Patients are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7+3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received will depend on response.

Drug: 7+3 (cytarabine and daunorubicin)

Interventions

Liposomal cytarabine-daunorubicin for injection DRUG

First induction: 100 units/m\^2 by 90-minute IV infusion on Days 1, 3, 5. Second induction: 100 units/m\^2 by 90-minute IV infusion on Days 1 and 3. Consolidation therapy: 65 units/m\^2 by 90-minute IV infusion on Days 1 and 3.

Arm A (liposomal cytarabine-daunorubicin for injection)

7+3 (cytarabine and daunorubicin) DRUG

First induction: 7+3 will be administered as: cytarabine at a dose of 100 mg/m\^2/day on Days 1 through 7 by continuous infusion, and daunorubicin at a dose of 60 mg/m\^2/day on Days 1, 2, and 3. Second induction: 5+2 will be administered as: cytarabine at a dose of 100 mg/m\^2/day on Days 1 through 5 by continuous infusion and daunorubicin at a dose of 60 mg/m\^2/day on Days 1 and 2. Consolidation therapy: 5+2 will be administered as: cytarabine at a dose of 100 mg/m\^2/day on Days 1 through 5 by continuous infusion, and daunorubicin at a dose of 60 mg/m\^2/day on Days 1 and 2.

Arm B (7+3)

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand the study and voluntarily sign informed consent.
• Male or female between 60-75 years of age (inclusive).
• Pathological diagnosis of AML according to 2022 WHO criteria (with at least 20% blasts in the peripheral blood or bone marrow) and fulfill of one of the following standards:
• Therapy related AML: t-AML must have a documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease;
• AML with a history of myelodysplasia: MDSAML must have bone marrow documentation of prior MDS;
• AML with a history of CMMoL: CMMoLAML must have bone marrow documentation of prior CMMoL;
• De novo AML with karyotypic abnormalities characteristic of MDS: de novoAML must have cytogenetics with abnormalities per WHO.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Laboratory values meet the following criteria:
• Serum creatinine≤2 × ULN;
• Serum total bilirubin≤2 × ULN, ≤3 × ULN for patients with liver involvement;
• Serum alanine aminotransferase or aspartate aminotransferase≤3 × ULN, ≤5 × ULN for patients with liver involvement.
• Cardiac function (LVEF) ≥ 50% by echocardiography or MUGA.
• QTcF (Fridericia's) for male\<450 ms, for female\<470 ms at screening.
• Male and female of childbearing potential must agree to use contraceptive measures (such as IUD, contraceptive or condom) during the study and within 6 months after the end of the study.

You may not qualify if:

• Acute promyelocytic leukemia; or favorable cytogenetics, including t(8;21) or inv16 if known at the time of randomization.
• Except for CMMoL, patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible.
• History of other malignancy within 3 years before randomization, expect for cancers that have been cured (basal cell or squamous cell carcinoma, superficial bladder cancer, carcinoma in situ of cervix and breast or prostate cancer with Gleason score of 6).
• Patients with clinical evidence of active CNS leukemia.
• Prior treatment for AML (except for hydroxyurea) or stem-cell transplantation.
• Administration of any therapy for MDS (conventional or investigational) within 2 weeks prior to of the first dose of study drug; use of hydroxyurea for the purpose of inhibiting rapid tumor proliferation within 24 hours before the first dose. Toxicities associated with prior MDS therapy have not recovered to grade 1 or less prior to start of treatment.
• Any major surgery or radiation therapy within 4 weeks.
• Patients with previous cumulative exposure to anthracyclines \>368 mg/m\^2 daunorubicin (or equivalent drug equivalent dose level).
• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent.
• Patients with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by NYHA Criteria (Class Ш or Ⅳ staging).
• Active or uncontrolled infection.
• Current evidence of invasive fungal infection (blood or tissue culture).
• Patients with known HIV, hepatitis B or hepatitis C infection.
• Patients who are hypersensitive to cytarabine, daunorubicin or liposomal products.
• Patients with a history of Wilson's disease or other copper-metabolism disorders.

Sponsors & Collaborators

• CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.: lead

Study Sites (1)

Institute of Hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences

Tianjin, China

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Leukemia, Myeloid, Acute

Interventions

Injections; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Clinical Trials Information Group officer

CONTACT

86-0311-69085587; ctr-contact@cspc.cn

Jianxiang Wang

CONTACT

86-022-23909120; wangjx@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2023
• First Posted: December 27, 2023
• Study Start: January 1, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 28, 2023

Record last verified: 2023-12

Locations

CN (1)