Clinical trial NCT05924750: A Study of BL-M11D1 in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Official title: A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BL-M11D1 in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-06-29
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Ia: To observe the safety and tolerability of BL-M11D1 in patients with relapsed/refractory acute myeloid leukemia to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of BL-M11D1. Ib: Further observe the safety and tolerability of BL-M11D1 at the recommended dose in phase Ia to determine the recommended dose in phase II clinical study (RP2D).


Eligibility criteria: Inclusion Criteria:

1. Voluntarily sign the informed consent and follow the requirements of the protocol.
2. No gender limit.
3. Age: ≥18 years old and ≤75 years old.
4. expected survival time ≥3 months.
5. Relapsed/refractory acute myeloid leukemia (AML) confirmed by histopathology and/or cytology;Patients who met the following criteria were defined as relapsed/refractory AML, including: newly diagnosed patients who failed to respond to 2 courses of standard regimens; Patients who relapsed within 12 months after complete remission after consolidation and intensive therapy; Patients relapsed after 12 months but failed to respond to conventional chemotherapy; Patients with two or more recurrences; Patients with persistent extramedullary leukemia and bone marrow blasts ≥5%; Investigator-assessed patients with relapsed or refractory acute myeloid leukemia who were not or were ineligible for/intolerant of other therapies.
6. ECOG ≤2.
7. Toxicity of previous antineoplastic therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 (except for asymptomatic laboratory abnormalities considered by the investigator, such as elevated alkaline phosphatase, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose; The exception was toxicity that was judged by the investigator to be not a safety risk, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism that was stable with hormone replacement therapy).
8. The level of organ function within 7 days before the first dose meets the following requirements and meets the following criteria:

   1. Liver function: Total bilirubin ≤1.5 ULN (Gilbert's syndrome ≤3 ULN), transaminase (AST/ALT) ≤2.5 ULN (subjects with liver tumor invasive changes ≤5.0 ULN), and/or alkaline phosphatase ≤5 ULN without correction with liver-protective drugs within 7 days before screening;
   2. renal function: creatinine (Cr) ≤1.5 ULN or creatinine clearance (Ccr) ≥50 mL/min (according to the center's calculation criteria);
   3. coagulation function: international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5ULN;
   4. proteinuria ≤2+ or ≤1000mg/24h.
9. For premenopausal women with childbearing potential, pregnancy tests must be performed within 7 days before starting treatment, serum/urine pregnancy must be negative, and must be non-lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Acute promyelocytic leukemia, acute transformation of chronic myeloid leukemia.
2. Antineoplastic therapy, including chemotherapy, biologic therapy, immunotherapy, definitive radiotherapy, major surgery (investigator-defined), or targeted therapy (including small-molecule tyrosine kinase inhibitors), has been administered within 4 weeks or 5 half-life cycles (whichever is shorter) before the first dose; Or palliative radiotherapy within 2 weeks before the first dose.
3. History of severe heart disease, such as left ventricular ejection fraction \< 50%, history of symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE v5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, history of myocardial infarction, unstable angina, etc.
4. Prolonged QT interval (QTc \> 450 msec in men or QTc \> 470 msec in women), complete left bundle branch block, and III degree atrioventricular block.
5. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory intestinal diseases and Hashimoto's thyroiditis, etc., excluding type I diabetes mellitus, hypothyroidism that can only be controlled by replacement therapy, and skin diseases without systemic treatment (such as vitiligo and psoriasis).
6. Other malignancies diagnosed within 5 years before the first dose, except for radical basal cell carcinoma, squamous cell carcinoma, and/or radical resection carcinoma in situ.
7. Poorly controlled hypertension (systolic blood pressure \&gt; 150 mmHg or diastolic blood pressure \&gt; 100 mmHg).
8. Patients with pulmonary disease grade ≥3 defined by CTCAE v5.0, current or previous interstitial lung disease (ILD).
9. Patients with central nervous system involvement.
10. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of the ingredients of BL-M11D1.
11. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
12. Human immunodeficiency virus (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBsAg positive; HBcAb positive and HBV-DNA copy number \> lower detection limit) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA \> lower detection limit).
13. Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
14. Presence of pleural, abdominal, pelvic or pericardial effusion with clinical symptoms or requiring repeated drainage.
15. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of last dose).
16. Pregnant or lactating women.
17. Other conditions for participation in the trial were not considered appropriate by the investigator.

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to 28 days after the first dose
measure: Phase Ia: Maximum tolerated dose (MTD)
timeFrame: Up to 28 days after the first dose
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to 28 days after the first dose
Secondary outcomes:
measure: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to 28 days after the first dose
measure: Tmax
timeFrame: Up to 28 days after the first dose
measure: T1/2
timeFrame: Up to 28 days after the first dose
measure: AUC0-t
timeFrame: Up to 28 days after the first dose
measure: CL (Clearance)
timeFrame: Up to 28 days after the first dose
measure: Ctrough
timeFrame: Up to 28 days after the first dose
measure: ADA (anti-drug antibody)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Haerbin
country: China
facility: Institute of Hematology, the First Hospital of Harbin
state: Heilongjiang
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shangdong
city: Shanghai
country: China
facility: Shanghai Tongji Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital，Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
name: Junyuan Qi, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
name: Jianxiang Wang, MS
role: PRINCIPAL_INVESTIGATOR
References: