FCN-338 in Combination With Azacitidine or Chemotherapy in Myeloid Neoplasms

Phase 2Active Not RecruitingNCT06858618

Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.47 enrolled

Overview

This is a Phase 2, open-label, multicenter study to safety \& tolerability, antitumor activity, and pharmacokinetics of FCN-338 in Combination with szacitidine (AZA) or chemotherapy(erythromycin, cytarabine(Ara-C)) in Patients with myeloid neoplasms

Primary Objectives:1.To assess the safety and tolerability of FCN-338 in combination with AZA or chemotherapy in patients with myeloid neoplasms. 2. To explore the antitumor activity of FCN-338 combination therapy in patients with myeloid neoplasms. Secondary Objectives: 1. To assess the pharmacokinetic profile of the FCN-338 combination therapy in patients with myeloid neoplasms.2. To assess the transfusion independence rate in patients with myeloid neoplasms. There were 2 cohorts based on different combination therapies and different indications. Cohort A is FCN-338 combined with AZA (75mg/m², SC, QD, D1-7) for the treatment in relapsed/refractory (R/R) acute myeloid leukemia (AML) patients. Cohort B is FCN-338 combined with intensive chemotherapy for first line (1L) fit AML patients. During the induction phase, patients will be treated with erythromycin (60 mg/m², IV, QD , D1-3) and Ara-C (100 mg/m², IV, QD, D1-7). Patients achieving partial remission (PR) will repeat induction phase once, and patients who do not reach PR after first cycle of induction phase and those who do not achieve complete remission (CR)/Complete remission with incomplete hematological recovery (CRi)/morphologic leukemia-free state (MLFS) after two cycles of induction phase will receive other new antitumor treatments. Patients who achieve CR/CRi/MLFS will undergo consolidation phase with medium- to high-dose Ara-C (1 to 3 g/m²/12h, 6 doses) for 3 to 4 cycles, with the exact dose and number of cycles determined by investigator. Patients with intermediate- to high-risk according to the 2017 European Leukemia Net (ELN) stratification will undergo a total of 24 cycles of maintenance phase after completion of consolidation phase. Maintenance phase will consist of 24 cycles, FCN-338 in combination with AZA (50 mg/m², d1-5) for the first 12 cycles and FCN-338 alone for the rest 12 cycles. FCN-338 will be administered once daily (QD), D1-14 per cycle during induction phase, consolidation phase and maintenance phase.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Safety Antitumor Activity PK Profile

Interventions

FCN-338 + AzacitidineCOMBINATION_PRODUCT

FCN-338 (400 or 600 mg, PO, QD, D1-28) combined with azacitidine (75mg/m², SC, QD, D1-7), 28 days/cycle

FCN-338 + erythromycin+ Ara-CCOMBINATION_PRODUCT

Induction phase: FCN-338(600 mg, QD, D1-14) , erythromycin (60 mg/m², IV, QD , D1-3) and Ara-C (100 mg/m², IV, QD, D1-7) for 1 to 2 cycles. Consolidation phase: FCN-338(600 mg, QD, D1-14) ,Ara-C (1 to 3 g/m²/12h, 6 doses) for 3 to 4 cycles Maintenance phase:FCN-338(600 mg, QD, D1-14) , azacitidine (50 mg/m², SC, QD, D1-5) for the first 12 cycles and FCN-338 (600 mg, QD, D1-14) alone for the rest 12 cycles

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusive Criteria 1. Age ≥18 years. 2. Cohort A: Patients diagnosed with R/RAML (≥5% blasts in the bone marrow) according to the WHO 2016 criteria \[excluding acute promyelocytic leukemia (APL) and BCR-ABL positive AML\], meeting any of the following definitions: 1\) Relapsed AML: Reappearance of leukemic cells in peripheral blood or ≥5% blasts in bone marrow after complete remission (CR, CRi) (excluding other causes such as bone marrow regeneration after consolidation treatment) or infiltration of leukemic cells outside the marrow; 2) Refractory AML: Ineffective after two cycles of standard treatment; Relapsed within 12 months after CR followed by consolidation treatment; Relapsed after 12 months but ineffective with standard chemotherapy; Relapsed two or more times; With persistent extramedullary leukemia. 3\. Cohort B: Patients diagnosed with 1L fit AML according to the WHO 2016 criteria \[excluding acute promyelocytic leukemia (APL) and BCR-ABL positive AML\]. 4\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2. 5. Expected survival time ≥ 3 months. 6. Adequate bone marrow and organ function. Exclusive Criteria 1. Patients with diagnosis of APL or BCR-ABL-positive AML patients or a history of prior myeloproliferative disease (MPN). 2. With known leukemic infiltration of the central nervous system. 3. Have received allogeneic hematopoietic stem cell transplantation or overt immune cell therapy, or autologous hematopoietic stem cell transplantation within 1 year. 4. Have active fungal, bacterial and/or viral infections including, but not limited to, active Human Immunodeficiency Virus (HIV), viral hepatitis B or C.

Locations (1)

Union hospital tongjimedical college huzhong university of science and technology

Wuhan, China

Outcomes

Primary Outcomes

Incidence of DLT

Incidence of DLT in DLT observation period

Time frame: At the end of Cycle 1 (each cycle is 28 days)

Title: composite CR rate (CRc)

The proportion of CR, CRi and MLFS patients in the efficacy analysis set (EAS)

Time frame: From the first dose to the end of maintenance phase, assessed up to 30 months

Minimal residual disease (MRD) negative rate

The proportion of AML patients with CR/CRi/MLFS who were negative for MRD.

Time frame: From the first dose to the end of maintenance phase, assessed up to 30 months

Secondary Outcomes

Transfusion Independence

The proportion of independence on red blood cell (RBC) and platelet transfusions among those patients who were dependent on RBC and platelet transfusions at baseline.

Time frame: From the first dose to the end of maintenance phase, assessed up to 30 months

Time to remission

Defined as the time from the first dose to the first observation of CR/CRi/MLFS

Time frame: From the first dose to the first observation of CR/CRi/MLFS, assessed up to 2 months

Event-free survival

Defined as the time from the first dose to induction failure or relapse or death from any cause (whichever occours first).

Time frame: From the first dose to induction failure or relapse or death from any cause (whichever occours first), assessed up to 54 months

Duration of remission

Defined as the time from the first observation of CR/CRi/MLFS to tumor progression or death from any cause(whichever occours first).

Data from ClinicalTrials.gov

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