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A Study of BL-M11D1 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Primary Purpose

Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
BL-M11D1
Sponsored by
Sichuan Baili Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Voluntarily sign the informed consent and follow the requirements of the protocol. No gender limit. Age: ≥18 years old and ≤75 years old. expected survival time ≥3 months. 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. ECOG ≤2. 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). The level of organ function within 7 days before the first dose meets the following requirements and meets the following criteria: 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; renal function: creatinine (Cr) ≤1.5 ULN or creatinine clearance (Ccr) ≥50 mL/min (according to the center's calculation criteria); coagulation function: international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5ULN; proteinuria ≤2+ or ≤1000mg/24h. 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: Acute promyelocytic leukemia, acute transformation of chronic myeloid leukemia. 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. 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. Prolonged QT interval (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, and III degree atrioventricular block. 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). 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. Poorly controlled hypertension (systolic blood pressure &gt; 150 mmHg or diastolic blood pressure &gt; 100 mmHg). Patients with pulmonary disease grade ≥3 defined by CTCAE v5.0, current or previous interstitial lung disease (ILD). Patients with central nervous system involvement. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of the ingredients of BL-M11D1. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT). 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). Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc. Presence of pleural, abdominal, pelvic or pericardial effusion with clinical symptoms or requiring repeated drainage. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of last dose). Pregnant or lactating women. Other conditions for participation in the trial were not considered appropriate by the investigator.

Sites / Locations

  • Anhui Provincial Hospital
  • Beijing Hospital
  • Institute of Hematology, the First Hospital of Harbin
  • Shengjing Hospital of China Medical University
  • Qilu Hospital of Shandong University
  • Shanghai Tongji Hospital
  • West China Hospital,Sichuan University
  • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Study treatment

Arm Description

Participants receive BL-M11D1 as intravenous infusion for the first cycle (4 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.

Outcomes

Primary Outcome Measures

Phase Ia: Dose limiting toxicity (DLT)
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Phase Ia: Maximum tolerated dose (MTD)
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .
Phase Ib: Recommended Phase II Dose (RP2D)
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-M11D1.

Secondary Outcome Measures

Treatment-Emergent Adverse Event (TEAE)
TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-M11D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M11D1.
Cmax
Maximum serum concentration (Cmax) of BL-M11D1 will be investigated.
Tmax
Time to maximum serum concentration (Tmax) of BL-M11D1 will be investigated.
T1/2
Half-life (T1/2) of BL-M11D1 will be investigated.
AUC0-t
AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.
CL (Clearance)
CL in the serum of BL-M11D1 per unit of time will be investigated.
Ctrough
Ctough is defined as the lowest serum concentration of BL-M11D1 prior to the next dose will be administered.
ADA (anti-drug antibody)
ADA of BL-M11D1 will be evaluated.
Phase Ib: Objective Response Rate (ORR)
ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
Phase Ib: Disease Control Rate (DCR)
The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]).
Phase Ib: Duration of Response (DOR)
The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.

Full Information

First Posted
June 16, 2023
Last Updated
October 8, 2023
Sponsor
Sichuan Baili Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05924750
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 2, 2023 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sichuan Baili Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Study treatment
Arm Type
Experimental
Arm Description
Participants receive BL-M11D1 as intravenous infusion for the first cycle (4 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.
Intervention Type
Drug
Intervention Name(s)
BL-M11D1
Intervention Description
Administration by intravenous infusion
Primary Outcome Measure Information:
Title
Phase Ia: Dose limiting toxicity (DLT)
Description
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Time Frame
Up to 28 days after the first dose
Title
Phase Ia: Maximum tolerated dose (MTD)
Description
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .
Time Frame
Up to 28 days after the first dose
Title
Phase Ib: Recommended Phase II Dose (RP2D)
Description
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-M11D1.
Time Frame
Up to 28 days after the first dose
Secondary Outcome Measure Information:
Title
Treatment-Emergent Adverse Event (TEAE)
Description
TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-M11D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M11D1.
Time Frame
Up to approximately 24 months
Title
Cmax
Description
Maximum serum concentration (Cmax) of BL-M11D1 will be investigated.
Time Frame
Up to 28 days after the first dose
Title
Tmax
Description
Time to maximum serum concentration (Tmax) of BL-M11D1 will be investigated.
Time Frame
Up to 28 days after the first dose
Title
T1/2
Description
Half-life (T1/2) of BL-M11D1 will be investigated.
Time Frame
Up to 28 days after the first dose
Title
AUC0-t
Description
AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.
Time Frame
Up to 28 days after the first dose
Title
CL (Clearance)
Description
CL in the serum of BL-M11D1 per unit of time will be investigated.
Time Frame
Up to 28 days after the first dose
Title
Ctrough
Description
Ctough is defined as the lowest serum concentration of BL-M11D1 prior to the next dose will be administered.
Time Frame
Up to 28 days after the first dose
Title
ADA (anti-drug antibody)
Description
ADA of BL-M11D1 will be evaluated.
Time Frame
Up to approximately 24 months
Title
Phase Ib: Objective Response Rate (ORR)
Description
ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
Time Frame
Up to approximately 24 months
Title
Phase Ib: Disease Control Rate (DCR)
Description
The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]).
Time Frame
Up to approximately 24 months
Title
Phase Ib: Duration of Response (DOR)
Description
The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.
Time Frame
Up to approximately 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Voluntarily sign the informed consent and follow the requirements of the protocol. No gender limit. Age: ≥18 years old and ≤75 years old. expected survival time ≥3 months. 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. ECOG ≤2. 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). The level of organ function within 7 days before the first dose meets the following requirements and meets the following criteria: 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; renal function: creatinine (Cr) ≤1.5 ULN or creatinine clearance (Ccr) ≥50 mL/min (according to the center's calculation criteria); coagulation function: international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5ULN; proteinuria ≤2+ or ≤1000mg/24h. 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: Acute promyelocytic leukemia, acute transformation of chronic myeloid leukemia. 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. 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. Prolonged QT interval (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, and III degree atrioventricular block. 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). 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. Poorly controlled hypertension (systolic blood pressure &gt; 150 mmHg or diastolic blood pressure &gt; 100 mmHg). Patients with pulmonary disease grade ≥3 defined by CTCAE v5.0, current or previous interstitial lung disease (ILD). Patients with central nervous system involvement. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of the ingredients of BL-M11D1. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT). 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). Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc. Presence of pleural, abdominal, pelvic or pericardial effusion with clinical symptoms or requiring repeated drainage. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of last dose). Pregnant or lactating women. Other conditions for participation in the trial were not considered appropriate by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hai Zhu, PHD
Phone
+8613980051002
Email
zhuhai@baili-pharm.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sa Xiao, PHD
Phone
+8615013238943
Email
xiaosa@baili-pharm.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Junyuan Qi, PHD
Organizational Affiliation
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jianxiang Wang, MS
Organizational Affiliation
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Anhui Provincial Hospital
City
Hefei
State/Province
Anhui
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Changcheng Zheng
Facility Name
Beijing Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hui Liu
Facility Name
Institute of Hematology, the First Hospital of Harbin
City
Haerbin
State/Province
Heilongjiang
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tiejun Gong
Facility Name
Shengjing Hospital of China Medical University
City
Shenyang
State/Province
Liaoning
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhuogang Liu
Facility Name
Qilu Hospital of Shandong University
City
Jinan
State/Province
Shangdong
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chunyan Ji
First Name & Middle Initial & Last Name & Degree
Chunyan Ji
First Name & Middle Initial & Last Name & Degree
Jingjing Ye
Facility Name
Shanghai Tongji Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ping Li
Facility Name
West China Hospital,Sichuan University
City
Chengdu
State/Province
Sichuan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu Wu
Facility Name
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yali Zhang
Phone
022-23909095
Email
ec@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Junyuan Qi
First Name & Middle Initial & Last Name & Degree
Jianxiang Wang

12. IPD Sharing Statement

Learn more about this trial

A Study of BL-M11D1 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

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