Clinical trial NCT05241093: A Study of HYML-122 and Cytarabine in Patients With FLT3 Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
Official title: A Single-arm, Open, Multicenter, Phase II Study to Investigator the Efficacy and Safety of HYML-122 and Cytarabine in Patients With FLT3 Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Relapsed or Refractory Acute Myeloid Leukemia (AML)
Lead sponsor: Tarapeutics Science Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-15
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: level 1: HYML-122 400mg bid (day1-day28) in combination with Cytarabine 100mg/m2 (day1-day7). each cycle is 28 days.

level2: HYML-122 600mg bid (day1-day28) in combination with Cytarabine 100mg/m2 (day1-day7). each cycle is 28 days.
Primary purpose: TREATMENT

Brief summary: This is a single-arm, open, multicenter, phase 2 study to evaluate the efficacy, safety and pharmacokinetics of HYLM-122 in combination with cytarabine in Chinese subjects with FLT3 positive relapsed or refractory acute myeloid leukemia.

Detailed description: This study will have two phases. Phase 1: the escalation phase is to establish the recommended phase 2 dose (RP2D) of HYML-122 given in combination with cytarabine.

Phase 2: the extension phase study will treat patients with FLT3 positive relapsed or refractory AML with HYML-122 in combination with cytarabine at the RP2D, and further evaluate efficacy and safety.

Eligibility criteria: Inclusion Criteria:

* Fully understand the procedures of the clinical study and participate voluntarily with signed and dated written informed consent form, comply with the requirements of the study protocol.
* Males and/or females at least 18 years old when signing the informed consent form.
* Histologically confirmed AML (defined using WHO criteria 2016) with one of the following: Refractory to at least 1 cycle of induction chemotherapy. Relapsed after achieving remission with a prior therapy.
* Subject is positive for FLT3 mutation in bone marrow or blood after completion of the subject's last interventional treatment.
* Eastern cooperative oncology group performance status (ECOG) ≤2 at screening.
* Life expectancy of at least 3 months.
* Women of childbearing potential have a negative pregnancy test at baseline and are willing to employ an effective method of contraception for the entire duration of study treatment and 6 months after the last dose.

Exclusion Criteria:

* Known or suspected allergies to any of the investigational drug composition (HYML-122, lactose, hydroxypropyl cellulose, hyposubstituted hydroxypropyl cellulose, silicon dioxide, magnesium stearate, titanium dioxide and polyethylene glycol).
* Medical history and surgical history excluded according to the protocol.
* Any previous medical treatment history exclude from the protocol.
* Abnormal laboratory results exclude from the protocol.
* Combination of treatments and/or drugs required during the study period and cannot be discontinued that excluded from the protocol.
* Alcohol abuse within 6 months prior to screening, defined as long-term drinking history, generally more than 5 years, equivalent to alcohol quantity ≥40g/d for men, ≥20g/d for women, or heavy drinking history within 2 weeks, equivalent to alcohol quantity ≥80g/d. alcohol volume (g) conversion formula=alcohol consumption (mL)\*alcohol content (%)\*0.8.
* Abortion less than 30 days prior to screening, pregnant and lactating women (currently breast-feeding or less than one year after delivery although not breast-feeding), women of childbearing potential who are not guaranteed effective contraception during the study, planning pregnancy or donating eggs or sperm within 6 months after the last dose.
* History of drug abuse or drug addicts.
* Subjects may not be able to complete the study duo to poor compliance or other reasons, or unsuitable for the study by the investigator's judgment.

Primary outcomes:
measure: ORR
timeFrame: up to 24 months
measure: composite complete remission (CRc) rate
timeFrame: up to 24 months.
Secondary outcomes:
measure: RFS
timeFrame: up to 24 months
measure: EFS
timeFrame: up to 24 months
measure: OS
timeFrame: up to 24 months
measure: DOR-CR
timeFrame: up to 24 months
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: up to 24 months
measure: Cmax,ss
timeFrame: at the end of Cycle 1 (each cycle is 28 days)
measure: Cmin,ss
timeFrame: at the end of Cycle 1 (each cycle is 28 days)
measure: Cav,ss
timeFrame: at the end of Cycle 1 (each cycle is 28 days)
measure: AUCss
timeFrame: at the end of Cycle 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Suzhou
country: China
facility: the First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Depei Wu, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References: