AML, Adult Clinical Trial
Official title:
A PhaseI/II, Multicenter, Open-label Clinical Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of the Menin Inhibitor BN104 in the Treatment of Patients With Relapsed/Refractory Acute Leukemia
The Phase I/II trial is to learn the safety, pharmacokinetics, and preliminary efficacy of BN104 taken once daily or twice daily in patients with acute lymphocytic leukemia or acute myeloblastic leukemia.
Status | Recruiting |
Enrollment | 90 |
Est. completion date | June 2027 |
Est. primary completion date | June 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Have been fully informed about the study and have voluntarily signed the ICF; 2. patients with relapsed/refractory acute leukemia (including AML, ALL, and mixed-spectrum leukemias, except acute promyelocytic leukemia) diagnosed according to the 2022 World Health Organization (WHO) criteria, and for whom there are no superior therapeutic alternatives as assessed by the investigator, and who meet at least one of the following criteria: - Primary refractory disease; - First relapse with duration of first remission = 12 months - Relapsed/refractory disease after 2 or more lines of therapy; - Relapse after allogeneic hematopoietic stem cell transplantation (patients who relapse after autologous hematopoietic stem cell transplantation and immune cell therapy [including, but not limited to, chimeric antigen receptor T-cells] may also be enrolled if there is no superior therapeutic regimen in the investigator's assessment); Notes: - Secondary AML or AML transformed by myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) may also be enrolled; - Control of peripheral blood leukocyte counts with hydroxyurea is allowed prior to study drug administration and for 2 weeks after initiation of study drug administration. 3. For Phase I dose-optimization and Phase II subjects, the combination of NPM1 mutation or KMT2A rearrangement should also be specified. 4. Age = 18 years; 5. ECOG score 0-2; 6. Adequate hepatic, renal, and cardiac functions 7. Expected survival of more than 12 weeks as judged by the investigator 8. Be able to perform treatments, visits, and undergo study-related testing as required by the protocol 9. 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 for 30 days after the last study dose. Postmenopausal women (>45 years of age and menopause for more than 1 year) and surgically sterilized women are not subject to this condition. Exclusion Criteria: 1. definite active central nervous system (CNS) leukemia (previous CNS leukemia that has been treated and controlled, but requires screening period lumbar puncture for cerebrospinal fluid examination for confirmation, or routine receipt of standard CNS prophylaxis are acceptable); 2. a known history of clinically significant liver disease, including viral or other hepatitis or cirrhosis 3. known human immunodeficiency virus (HIV) infection; 4. pregnant (positive screening pregnancy test) or lactating females; 5. 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); 6. 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; 7. has received autologous hematopoietic stem cell transplantation (ASCT) or chimeric antigen receptor T cell (CAR T) therapy within 60 days prior to screening, or has not recovered from toxicity associated with ASCT or CAR-T therapy 8. allogeneic hematopoietic stem cell transplantation has been performed within 100 days prior to screening, or the patient is still comorbid with active acute or chronic graft-versus-host disease, or the patient is still in need of immunosuppressive therapy; 9. anti-leukemia therapy, including chemotherapy, radiotherapy, hormone therapy, or immunotherapy (excluding hydroxyurea) within 2 weeks prior to the start of study treatment; 10. prior participation in a clinical study of another drug less than 2 weeks or 5 half-lives for small molecules and less than 4 weeks or 5 half-lives for large molecules (e.g., antibody-based drugs) from the last dose, whichever is shorter 11. prior treatment with targeted menin; 12. prior toxic reactions to anti-leukemia therapy that have not returned to grade 0 or 1 levels (except alopecia areata) 13. uncontrolled active infection: - Patients with non-serious infectious complications (e.g., oral Candida infection or uncomplicated urinary tract infection) 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 has been found, and patients with normal body temperature for more than 72 hours without antipyretic medication may be enrolled; 14. subjects with known dysphagia, short bowel syndrome, gastroparesis, or other conditions that limit oral drug intake or gastrointestinal absorption; 15. a history of severe allergy to menin inhibitors or hypersensitivity to any of the components of BN104 16. inadequate patient compliance with participation in this clinical study as judged by the investigator; 17. 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. |
Country | Name | City | State |
---|---|---|---|
China | The First Affiliated Hospital of Soochow University | Suzhou |
Lead Sponsor | Collaborator |
---|---|
BioNova Pharmaceuticals (Shanghai) LTD. |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | PhaseI Incidence of Dose Dose limiting toxicities(DLTs) | DLTs will be evaluated at the end of cycle 1(28 days after receiving BN104) for each dose level by evaluating abnormal laboratory examinations by the Investigator. | DLT last 28days(at the end of cycle 1 for each dose) | |
Primary | PhaseI Incidence of serious adverse events(SAEs) | SAEs will be recorded in the eCRF from time of the signing informed consent through 30 days after the last dose of BN104. | 36 month | |
Primary | PhaseII efficacy assessment | To assess the preliminary anti-tumor activity of BN104 based on Complete response (CR), Complete response with partial recovery of hematology (CRh), Complete response with incomplete hematological recovery (CRi) assessed by the Investigator | 36 month | |
Secondary | Phase I/II Evaluate the number and frequency of adverse events (AEs) | Evaluate the number and frequency of adverse events (AEs) by evaluating abnormal laboratory examinations by the Investigator at each clinical visit from time of the signing informed consent through 30 days after the last dose of BN104. | 36 months | |
Secondary | Phase I/II Evaluate patient vital signs | Evaluate vital signs, including body temperature, heart rate, respiration rate, and blood pressure by the Investigator at each clinical visit before taking BN104. | 36 months | |
Secondary | Phase I/II Evaluate electrocardiogram (ECG) assessments | Evaluate electrocardiogram (ECG) assessments by the Investigator Prior to any examination at each clinical visit to monitor heart rate, R-R interval, QT interval and QTcF interval, QRS, and P-R interval times. | 36 months | |
Secondary | Phase I/II pharmacokinetic Maximum concentration (Cmax) | To characterized Maximum Plasma Concentration [Cmax] of BN104 by collecting and evaluating the serum at the protocol specified time points. | 36 months | |
Secondary | Phase I/II pharmacokinetic Peak time(Tmax) | To characterized Peak time(Tmax) of BN104 by collecting and evaluating the serum at the protocol specified time points | 36 months | |
Secondary | Phase I/II pharmacokinetic Clearance half-life (T1/2) | To characterized Clearance half-life (T1/2) of BN104 by collecting and evaluating the serum at the protocol specified time points | 36 months | |
Secondary | Phase I/II pharmacokinetic Area under the blood concentration-time curve (AUC0-t) | To characterized Area under the blood concentration-time curve (AUC0-t) of BN104 by collecting and evaluating the serum at the protocol specified time points. | 36 months | |
Secondary | Phase I/II pharmacokinetic metabolite M1 | To characterized BN104 major metabolite M1 by collecting and evaluating the serum at the protocol specified time points. | 36 months | |
Secondary | Phase I/II efficacy assessment based on Complete response (CR) | To assess the preliminary anti-tumor activity of BN104 based on Complete response (CR) assessed by the Investigator at Cycle2. cycle3 and every 2 cycles thereafter through peripheral blood tests, detection of bone marrow primitive cell ratio and other morphological changes by bone marrow aspiration/biopsy | 36 months | |
Secondary | Phase I/II efficacy assessment based on Complete response with partial recovery of hematology (CRh) | To assess the preliminary anti-tumor activity of BN104 based on Complete response with partial recovery of hematology (CRh) assessed by the Investigator at Cycle2. cycle3 and every 2 cycles thereafter through peripheral blood tests, detection of bone marrow primitive cell ratio and other morphological changes by bone marrow aspiration/biopsy | 36 months | |
Secondary | Phase I/II efficacy assessment based on Complete response with incomplete hematological recovery (CRi) | To assess the preliminary anti-tumor activity of BN104 based on Complete response with incomplete hematological recovery (CRi) assessed by the Investigator at Cycle2. cycle3 and every 2 cycles thereafter through peripheral blood tests, detection of bone marrow primitive cell ratio and other morphological changes by bone marrow aspiration/biopsy | 36 months | |
Secondary | Phase I/II efficacy assessment Objective response rate (ORR) | To assess the preliminary anti-tumor activity of BN104 based on Objective response rate (ORR) assessed by the Investigator at Cycle2. cycle3 and every 2 cycles thereafter through peripheral blood tests, detection of bone marrow primitive cell ratio and other morphological changes by bone marrow aspiration/biopsy | 36 months | |
Secondary | Phase I/II efficacy assessment based on Duration of response (DOR) | To assess the preliminary anti-tumor activity of BN104 based on Duration of response (DOR) assessed by the Investigator at Cycle2. cycle3 and every 2 cycles thereafter through peripheral blood tests, detection of bone marrow primitive cell ratio and other morphological changes by bone marrow aspiration/biopsy | 36 months | |
Secondary | Phase I/II efficacy assessment based on Event-free survival (EFS) | To assess the preliminary anti-tumor activity of BN104 based on Event-free survival (EFS) assessed by the Investigator at Cycle2. cycle3 and every 2 cycles thereafter through peripheral blood tests, detection of bone marrow primitive cell ratio and other morphological changes by bone marrow aspiration/biopsy | 36 months | |
Secondary | Phase I/II efficacy assessment based Relapse-free survival (RFS) | To assess the preliminary anti-tumor activity of BN104 based Relapse-free survival (RFS) assessed by the Investigator at Cycle2. cycle3 and every 2 cycles thereafter through peripheral blood tests, detection of bone marrow primitive cell ratio and other morphological changes by bone marrow aspiration/biopsy | 36 months | |
Secondary | Phase I/II efficacy assessment based on Overall survival (OS) | To assess the preliminary anti-tumor activity of BN104 based on Overall survival (OS) assessed by the Investigator at Cycle2. cycle3 and every 2 cycles thereafter through peripheral blood tests, detection of bone marrow primitive cell ratio and other morphological changes by bone marrow aspiration/biopsy | 36 months | |
Secondary | Phase I/II efficacy assessment Cumulative relapse rate (CIR) | To assess the preliminary anti-tumor activity of BN104 based on Cumulative relapse rate (CIR) assessed by the Investigator at Cycle2. cycle3 and every 2 cycles thereafter through peripheral blood tests, detection of bone marrow primitive cell ratio and other morphological changes by bone marrow aspiration/biopsy | 36 months | |
Secondary | PhaseI pharmacokinetic biomarkers | Changes in pharmacokinetic biomarkers (e.g., HOXA9, MEIS1, CD11b, etc.) before and after BN104 administration, and correlations with dosing and efficacy | 36 months | |
Secondary | correlation between specific gene alterations and clinical efficacy | The correlation between specific gene alterations (such as NPM1 mutation, KMT2A rearrangement) and other gene alterations (such as FLT3 mutation/fusion, TP53 mutation, NUP98 fusion, etc.), and clinical efficacy. | 36 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT04623944 -
NKX101, Intravenous Allogeneic CAR NK Cells, in Adults With AML or MDS
|
Phase 1 | |
Not yet recruiting |
NCT06313437 -
Revumenib in Combination With 7+3 + Midostaurin in AML
|
Phase 1 | |
Terminated |
NCT04079738 -
Study Augmenting TAK-659 Action in Relapsed/Refractory AML by Addition Ofthe Proteasome Inhibitor Ixazomib
|
Phase 1/Phase 2 | |
Recruiting |
NCT06027853 -
Natural Killer(NK) Cell Therapy Targeting CLL1 in Acute Myeloid Leukemia
|
Phase 1 | |
Completed |
NCT02986620 -
Italian Registry on the Prevalence of IDH1/IDH2 Mutations in Patients With Acute Myeloid Leukemia
|
||
Recruiting |
NCT05601466 -
Natural Killer(NK) Cell Therapy for Acute Myeloid Leukemia
|
Phase 1 | |
Recruiting |
NCT06066905 -
A Study of Chidamide With AZA in MRD Positive AML After Transplant
|
N/A | |
Recruiting |
NCT05909501 -
Assessment of Geriatric Evaluations Impact on New AML Guidance
|
||
Terminated |
NCT04614636 -
FT538 in Subjects With Advanced Hematologic Malignancies
|
Phase 1 | |
Not yet recruiting |
NCT06420063 -
Sequential CAR-T Cells Targeting CD33/CD123 in Patients With Acute Myelocytic Leukemia AML
|
Phase 1/Phase 2 | |
Withdrawn |
NCT04128020 -
Azacitidine Plus Nivolumab Following Reduced-intensity Allogeneic PBSC Transplantation for Patients With AML and High-risk Myelodysplasia
|
Phase 1 | |
Active, not recruiting |
NCT04749355 -
Phase 2, Open-Label, Single Arm Study, With BST-236 in Adults With R/R AML or Higher-Risk MDS
|
Phase 2 | |
Active, not recruiting |
NCT04755244 -
A Study of Evorpacept (ALX148) With Venetoclax and Azacitidine for Acute Myeloid Leukemia (ASPEN-05)
|
Phase 1/Phase 2 | |
Completed |
NCT03194685 -
Study of FF-10101-01 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
|
Phase 1/Phase 2 | |
Recruiting |
NCT03884829 -
A Phase I Study of CYC140, a PLK-1 Inhibitor, in Advanced Leukemias or MDS
|
Phase 1 | |
Active, not recruiting |
NCT05177731 -
Venetoclax + Decitabine vs. "7+3" Induction Chemotherapy in Young AML
|
Phase 3 | |
Not yet recruiting |
NCT06377579 -
OBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia
|
||
Recruiting |
NCT05025098 -
Precision Therapy Versus Standard Therapy in AML and MDS in Elderly
|
Phase 2 | |
Not yet recruiting |
NCT06263387 -
Results From a French Temporary Utilization Authorization of First-line Acute Myeloid Leukemia (AML) Patients Ineligible for Intensive Chemotherapy (IC), Treated With Venetoclax Azacitidine
|
||
Not yet recruiting |
NCT06188182 -
D-index as a Predictor of Complication of Treatment of Patients With Acute Myeloid Leukemia
|