BN104 in Combination With Chemotherapy or Targeted Agents for Acute Myeloid Leukemia

NCT06746519 | Recruiting Phase 1

• 1 other identifier: BN104-105
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

The Phase I/II trial is to learn the safety, pharmacokinetics, and preliminary efficacy of BN104 taken twice daily combined with Intensive Chemotherapy or Venetoclax/Azacitidine in patients with acute myeloblastic leukemia.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety and tolerability of BN104 in combination with Venetoclax/Azacitidine or intensive chemotherapy

  Incidence of DLTs (evaluated at the end of cycle 1 for each dose level);

  At the end of Cycle1 (Cycle1 Day28)

Secondary Outcomes (8)

• Peak concentration (Cmax)

  At the first Cycle, and Day1 of Cycle 2 (each cycle is 28days)

• Auc(0-last）

  At the first Cycle, and Day1 of Cycle 2 (each cycle is 28days)

• CR

  At the screening, Cycle1Day28, Cvcle4Day1, Cycle7Day1, Cycle10Day1 (do the efficacy assessment each 3 cycles, each cycle is 28 days)

• ORR (CR+CRh+CRi+PR+MLFS)

  At the screening, Cycle1Day28, Cycle4Day1, Cycle7Day1, Cycle10Day1 (do the efficacy assessment each 3 cycles, each cycle is 28 days)

• DOR

  At the screening, Cycle1Day28, Cycle4Day1, Cycle7Day1, Cycle10Day1 (do the efficacy assessment each 3 cycles, each cycle is 28 days)

Other Outcomes (3)

• MRD negativity rate

  At the screening, Cycle1Day28, Cycle4Day1, Cycle7Day1, Cycle10Day1 (do the efficacy assessment each 3 cycles, each cycle is 28 days)

• PD: MEIS1

  At the screening and the end of Cycle 1 (each cycle is 28 days)

• PD: HOXA9

  At the screening and the end of Cycle 1 (each cycle is 28 days)

Study Arms (3)

BN104 Combined Intensive Chemotherapy in patients with newly diagnosed AML

EXPERIMENTAL

Drug: BN104 combined Intensive Chemotherapy or Venetoclax/Azacitidine

BN104 Combined Venetoclax/Azacitidine in patients with newly diagnosed AML

EXPERIMENTAL

Drug: BN104 combined Intensive Chemotherapy or Venetoclax/Azacitidine

BN104 Combined Venetoclax/Azacitidine in patients with relapsed/refractory AML

EXPERIMENTAL

Drug: BN104 combined Intensive Chemotherapy or Venetoclax/Azacitidine

Interventions

BN104 combined Intensive Chemotherapy or Venetoclax/Azacitidine DRUG

The starting dose cohort(200mg BID N104) combined Intensive Chemotherapyor Venetoclax/Azacitidine. Each treatment cycle is anticipated to be 28 days in length, although cycle delays may be made due to delayed count recovery.

BN104 Combined Intensive Chemotherapy in patients with newly diagnosed AML; BN104 Combined Venetoclax/Azacitidine in patients with newly diagnosed AML; BN104 Combined Venetoclax/Azacitidine in patients with relapsed/refractory AML

Eligibility Criteria

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

You may qualify if:

• Have been fully informed about the study and have voluntarily signed the ICF;
• Patients with newly diagnosed primary AML according to the 2022 World Health Organization (WHO) criteria (Groups A and B) or patients with relapsed/refractory AML who have been previously treated with menin inhibitor monotherapy (Group C) and have an intermediate or poor prognosis according to the 2022 ELN Risk Stratification, as well as a defined combination of NPM1 mutation or NUP98 rearrangement or KMT2A rearrangement
• Peripheral blood leukocyte count ≤ 25 x 109/L (limited to patients enrolled in groups B and C, where hydroxyurea is allowed to control peripheral blood leukocyte count)
• Aged 18 years or older;
• ECOG (GroupA and B:0,1,2; GroupC:0,1,2,3)
• For patients in group B, unfit for intensive chemotherapy is defined as:≥75 years of age or;Age ≥18 years and age \<75 years with any of the following co-morbidities;ECOG score of 2 or 3;Cardiac history: congestive heart failure requiring treatment, or ejection fraction ≤50%, or chronic stable angina;DLCO ≤ 65% or FEV1 ≤ 65%;Creatinine clearance ≥30 ml/min and \<45 ml/min;Liver injury total bilirubin \> 1.5 x ULN but ≤ 3 x ULN.
• For patients in group C, previous failed treatment with menin inhibitors is required;
• adequate hepatic, renal, and cardiac function, as defined:Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal range (ULN);Total bilirubin ≤ 1.5 x ULN\* and in patients with Gilbert disease, total bilirubin ≤ 3 x ULN;Creatinine clearance ≥ 45 ml/min\* as estimated by the Cockcroft-Gault formula (if \<45 ml/min, enrollment is allowed if creatinine ≤ 130 µmol/L); Left ventricular ejection fraction ≥ 45%\*; Note: In Phase II studies, ALT or AST may be relaxed to ≤5 x ULN if the investigator assesses that the elevated ALT or AST is due to leukemia invasion of the liver;For patients \<75 years of age enrolled in Group B, total bilirubin ≤ 3 × ULN, creatinine clearance ≥ 30 ml/min, or left ventricular ejection fraction \< 50% are allowed;
• for patients with D-dimer test result \> 5×ULN in the screening period, relevant tests (e.g. review of coagulation function after a certain time interval, ultrasound of deep veins of the lower limbs, etc.) are required to exclude deep vein thrombosis, hypercoagulable state of blood and disseminated intravascular coagulation before enrollment;
• expected survival of more than 12 weeks as judged by the investigator;
• Be willing to attend study visits as required by the study protocol
• female patients of childbearing potential or male patients whose female partners are of childbearing potential must agree to use an effective method of contraception, such as a double-barrier method of contraception, condoms, oral or injectable contraceptives, and intrauterine devices (IUDs), for the duration of the study and within 30 days of the last study dose. Postmenopausal women (\>45 years of age and menopause of more than 1 year) and surgically sterilized women are exempt from this condition.

You may not qualify if:

• have active central nervous system (CNS) leukemia;
• a known history of clinically significant liver disease, including viral or other hepatitis or cirrhosis:Positive hepatitis B surface antigen (HBsAg) serology requires a negative hepatitis B virus (HBV) DNA test for enrollment; For patients with hepatitis C virus (HCV) antibody serology positive, a negative HCV RNA test result is required for enrollment.
• known human immunodeficiency virus (HIV) infection;
• pregnant (positive screening pregnancy test) or lactating females;
• meet any of the following cardiac-related criteria:Hereditary long QT interval syndrome or QTcF \> 450 msec;Various clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting within 6 months prior to enrollment, congestive heart failure graded by the New York Heart Association (NYHA) as grade 2 or higher (inclusive);
• the patient has suffered from other malignant tumors within the past 5 years, except for radically treated basal cell carcinoma of the skin, carcinoma in situ of the breast or carcinoma in situ of the cervix;
• have received prior anti-leukemia therapy (for patients in Groups A and B), except for the following: use of hydroxyurea or leukocyte monocloning for control of white blood cell count, or treatment with all-trans retinoic acid due to initial suspicion of acute promyelocytic leukemia, or use of nondemethylating medications for the treatment of MDS
• pre-existing treatment with targeted menin (for Group A and B patients)
• pre-existing non-hematologic toxicities that have not returned to grade 0 or 1 (except alopecia areata);
• patients who have had a chest CT within 1 month prior to screening and suggestive of pulmonary nodules need to undergo T-SPOT (T-cell spotting test for tuberculosis infection) during the screening period, and those with positive results need to be excluded (no additional tests are required if no chest CT has been performed within 1 month prior to screening);
• uncontrolled active infection:Patients with non-serious infectious complications (e.g., oral Candida infection or uncomplicated urinary tract infection, etc.) for which oral/topical anti-infective therapy is being applied may be enrolled;Patients with severe infections requiring hospitalization or intravenous antibiotic therapy within 14 days prior to enrollment, patients with no evidence of infection, and patients receiving prophylactic anti-infective, antifungal, or antiviral therapy for prolonged neutropenia may be enrolled;Patients treated with intravenous antibiotics or hospitalized for febrile neutropenia, but no evidence of infectious etiology is found, and patients with a normal temperature for more than 72 hours without antipyretic medication may be enrolled;
• patients with known dysphagia, short bowel syndrome, gastroparesis, or other conditions that limit oral drug intake or gastrointestinal absorption;
• patients with a history of severe allergy to menin inhibitors or hypersensitivity to any component of BN104
• inadequate patient compliance with participation in this clinical study as judged by the investigator
• any other disease, metabolic abnormality, physical examination abnormality, or clinically significant laboratory test abnormality that, in the judgment of the investigator, gives reason to suspect that the patient has a disease or condition that is inappropriate for the use of the study medication, or that will interfere with the interpretation of the results of the study, or that places the patient at high risk.

Sponsors & Collaborators

• Chen Suning: lead
• BioNova Pharmaceuticals (Shanghai) LTD.: collaborator

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Suning Chen, Doctor

CONTACT

051265223637; chensuning@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 3, 2024
• First Posted: December 24, 2024
• Study Start: December 25, 2024
• Primary Completion: December 30, 2025
• Study Completion (Estimated): June 30, 2027
• Last Updated: December 24, 2024

Record last verified: 2024-12

Locations

CN (1)