Clinical trial NCT06656494: ICP-248 in Combination with Azacitidine in Treatment-Naïve Subjects with Acute Myelogenous Leukemia(AML) or Previously Treated Relapsed/Refractory Subjects with Acute Myelogenous Leukemia(R/R AML).
Official title: A Phase 1 Study of ICP-248 in Combination with Azacitidine in Treatment-Naïve Subjects with Acute Myelogenous Leukemia Who Are Not Eligible for Standard Anthracycline-Based Induction or Previously Treated Relapsed/Refractory Subjects with Acute Myelogenous Leukemia.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-10-24
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Evaluate the safety, tolerability , pharmacokinetics , and preliminary efficacy of ICP-248 in Combination with azacitidine in Patients with Acute Myelogenous Leukemia . This study consists of two parts: Part 1 dose escalation period and Part 2 dose expansion period.


Eligibility criteria: Inclusion Criteria:

* Eligible subjects must meet all of the following criteria:

  1. Subject must have confirmation of diagnosis of AML, except for acute promyelocytic leukemia (APL) per 2016 World Health Organization (WHO) criteria.
  2. Previously treated relapsed/refractory AML subjects per 2017 European Leukemia Net (ELN) criteria.
  3. Treatment-naïve AML subjects should be:

     * ≥60 years of age;OR
     * ≥18 years and \<60 years will be eligible if the subject has at least one of the following co-morbidities, which make the subject unfit for intensive chemotherapy:

       1. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 2 - 3;
       2. History of congestive heart failure requiring treatment or Ejection Fraction (EF) ≤ 50% or chronic stable angina;
       3. Clinically significant respiratory failure or diffusing capacity for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1)

          ≤ 65%;
       4. Creatinine clearance ≥ 30 mL/min to \< 45 mL/min (calculated by Cockcroft Gault formula);
       5. Total bilirubin \> 1.5 to ≤ 3.0 ×upper limit of normal (ULN);
       6. Any other comorbidity that the Investigator judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Sponsor medical monitor before study enrollment.
  4. Subject must have a projected life expectancy of at least 12 weeks.
  5. Subject must have adequate renal function as demonstrated by a creatinine clearance≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft-Gault formula.
  6. Subject must have adequate liver function.

Exclusion Criteria:

1. Previously treated subject, who are refractory to previous azacitidine-based therapy defined as failure to achieve CR/CRi/MLFS per 2017 ELN criteria or intolerable to previous azacitidine-based treatment defined as discontinuation from azacitidine-based therapy due to clearly documented toxicity.
2. Previously treated subject, who are refractory to previous BCL-2 inhibitor-based therapy defined as failure to achieve CR/CRi/MLFS per 2017 ELN criteria or intolerable to previous BCL-2 inhibitor-based treatment defined as discontinuation from BCL-2 inhibitor-based therapy due to clearly documented toxicity.
3. Subject has acute promyelocytic leukemia (French-American-British Class M3 AML) or AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1.
4. Subject has known central nervous system (CNS) leukemia.
5. Subject has a history of myeloproliferative neoplasm (MPN) including polycythemia vera, myelofibrosis, essential thrombocythemia, or chronic myelogenous leukemia.
6. Subject has a white blood cell count \> 25 × 109/L (Cytoreductive therapy for leucocytosis are permitted to meet this criterion).
7. The serologic status suggestive of active hepatitis B or C virus infection.
8. History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.
9. Subjects have another active malignancy within the past 2 years before study entry, except for who have received curatively treated.
10. History of significant cardiovascular disease.

Primary outcomes:
measure: Incidence, type, and severity of dose-limiting toxicity (DLT).
timeFrame: 2.5 years
measure: Recommended phase II dose (RP2D) and/or maximum tolerated dose (MTD).
timeFrame: 2.5 years
measure: The incidence, nature, and severity of adverse events (AEs) as assessed per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) criteria.
timeFrame: 2.5 years
measure: Composite complete remission rate by Investigator per ELN 2017 criteria.
timeFrame: 2.5 years
measure: Composite complete remission rate by completion of cycle 2 by Investigator per ELN 2017 criteria.
timeFrame: 2.5 years
Secondary outcomes:
measure: Composite complete remission rate: The proportion of subjects with complete remission (CR) and CR with incomplete hematologic recovery (CRi) by Investigator per European Leukemia Net (ELN) 2017 criteria.
timeFrame: 2.5 years
measure: Composite complete remission rate by completion of cycle 2 by Investigator per ELN 2017 criteria.
timeFrame: 2.5 years
measure: The incidence, nature, and severity of adverse events (AEs) as assessed per NCI-CTCAE v5.0 criteria.
timeFrame: 2.5 years
measure: Maximum concentration (Cmax)of ICP-248.
timeFrame: 2.5 years
measure: Area under the curve (AUC) of ICP-248.
timeFrame: 2.5 years
measure: Time of maximum observed plasma(Tmax)of ICP-248.
timeFrame: 2.5 years
measure: Trough concentration(Ctrough) of ICP-248.
timeFrame: 2.5 years
measure: Apparent clearance (CL/F) of ICP-248.
timeFrame: 2.5 years
measure: Partial Response (PR) by investigator per ELN 2017 criteria.
timeFrame: 2.5 years
measure: Overall survival (OS) by investigator per ELN 2017 criteria.
timeFrame: 2.5 years
measure: Duration of Response (DOR) by investigator per ELN 2017 criteria.
timeFrame: 2.5 years
measure: Event-free Survival (EFS) by investigator per ELN 2017 criteria.
timeFrame: 2.5 years
measure: Relapse-free Survival (RFS) by investigator per ELN 2017 criteria.
timeFrame: 2.5 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: