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A Phase I Study of BC3402 as a Single Agent in Patients With MDS and CMML

Primary Purpose

Hematologic Malignancy

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
BC3402 Injection
Sponsored by
Biocity Biopharmaceutics Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancy focused on measuring MDS and CMML

Eligibility Criteria

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

Inclusion Criteria: The subject must be able to understand and voluntarily sign the informed consent form; Subjects were 18 years old or above when they signed the informed consent form; Subjects mast be willing to undergo serial bone marrow aspirate procedures on the study; Morphologically confirmed diagnosis as extremely low risk, low risk, intermediate risk, high risk, extremely high risk MDS (IPSS-R classification) or CMML according to WHO (2016) diagnostic criteria, and WBC<13* 10^9/L (allowed to receive hydroxyurea or leukocyte removal before enrollment to reduce WBC count), and: 4.1 According to IPSS-R, patients diagnosis as extremely low risk, low risk or intermediate risk MDS must meet one or more of the following criteria: Patients who are RBCs and/or platelets transfusion-dependent , must receive stable infusion 2U/month above for 3 months before the first dose; Patients who are RBCs transfusion-dependent must Erythropoiesis stimulating agents (ESAs) failure or intolerant ; Patients who are RBCs transfusion-dependent without ESA treatment mast have serum erythropoietin level >500 U/L ; MDS patients with isolated del (5q) ("5q syndrome") must have disease progression or intolerance during lenalidomide treatment; Platelet transfusion dependent patients must be treated with thrombopoietin receptor agonist (TPO-RA) for relapse/refractory or intolerance; Persistent (>3 months) neutrophil absolute count is lower than 1.5 before screening × 10^9/L; 4.2 MDS and CMML patients rated as high-risk or extremely high-risk according to IPSS-R: The monotherapy of demethylated drugs (HMA) failed (4 cycles of decitabine treatment or 6 cycles of azacytidine treatment) or was not tolerated; Not suitable for intensive treatment; CMML patients must fail or not tolerate at least one previous treatment (including but not limited to hydroxyurea treatment, HMA treatment, etc.); 5. Patient has an Eastern Cooperative Oncology Group(ecog) status between 0 and1; 6. Expected survival time > 3 months; 7. White blood cell count (WBC) ≤ 25 × 103/μL within 7 days prior to the first dose (hydroxycarbamide or leukapheresis is allowed to meet this criterion) 8. Platelet > 30 × 10^9/L before screening; 9. Adequate renal function: (2) Serum creatinine ≤ 1.5 × Upper limit of normal value (ULN), and creatinine clearance ≥ 45 mL/min; If the urine protein is qualitative ≥ 2+, the 24-hour urine protein quantity shall be less than 3.5g; 10. Adequate liver function: (3) Total serum bilirubin ≤ 1.5 × ULN (except Gilbert syndrome, this kind of subjects only meet the requirements of direct bilirubin ≤ 1.5 × ULN); (4) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; 11. When screening, serum or urine pregnancy test (for female patients with fertility) was negative; 12. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions guidelines and be willing to undergo a bone marrow aspirate and/biopsy at screening, during and at the end of therapy on this study. 13. Male and female patients with fertility must agree to use medically approved contraceptive methods throughout the study period and continue to use them until 6 months after the last treatment of BC3402. Exclusion Criteria: Suitable and willing to accept hematopoietic stem cell transplantation (allogeneic or autologous); Immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc., were used within 2 weeks before the first use of the test drug; 3. Prior treatment with immunomodulatory agents including but not limited to thymosin, interleukin-2, and interferon within 2 weeks prior to the first dose of study drugs. Patients who have used any Chinese herbal medicine or traditional Chinese medicine with anti-tumor activity within 2 weeks prior to the first dose of study drugs. Patients who received live attenuated vaccine within 4 weeks prior to the first dose of study drug. Prior treatment with an investigational drug within 4 weeks or 5 half-lives of the agent (whichever is longer) before the planned first dose of study drug. The washout period for biologic agents should be 28 days since the last dose. Prior exposure to TIM-3 targeted therapy at any time. Participants receiving chemotherapy within 14 days or 5 half lives (whichever is longer) before the first dose of study treatment; Major organ surgery or significant trauma or radiotherapy within 2 weeks before entering the study; Have received systemic glucocorticoid (prednisone>10mg/day or equivalent dose of the same drug) or other immunosuppressive drugs within 2 weeks before the first use of the study drug; Active infections or other severe infections requiring systemic antibiotics, antiviral or antifungal drugs within 2 weeks before the first administration of the study treatment. Except for those who are treated with anti infection prevention according to local guidelines or the judgment of the researcher. Known malignant tumors in progress or requiring active treatment in the past 5 years (except those diagnosed in the study). The exceptions to this exclusion criterion are as follows: basal cell carcinoma and squamous cell skin carcinoma completely resected; And completely resected carcinoma in situ of any type; Active hepatitis B or C, history of HIV infection, active syphilis; Patients with autoimmune diseases; Known uncontrolled central nervous system (CNS) involvement; Patients with history of serious cardiovascular and cerebrovascular diseases, including but not limited to, (1)Serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, Ⅱ - Ⅲ degree atrioventricular block ect. (2) During the screening period, 12 lead electrocardiogram (ECG) was measured for three times in the research center. According to the average value of the three times calculated by the QTc formula of the instrument used in the center, QTc interval> 470ms; (3) occurrence of acute coronary heart failure, acute congestive syndrome, aortic dissection, stroke or other grade 3 or above cardiovascular and cerebrovascular events within 6 months prior to the first dose of study drug (4) Patients with history of New York Heart Society (NYHA) class≥ II, or left ventricular ejection fraction (LVEF) < 50%; (5) Clinically uncontrollable hypertension 17. Mental disorders or poor compliance; 18. Patients who are being pregnant or breastfeeding. 19.Patients with other serious systemic diseases or conditions who are deemed unsuitable to participate in this clinical study at the judgement of the Investigator

Sites / Locations

  • The First Affiliated Hospital of Jinan UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BC3402 treatment group

Arm Description

BC3402 as a single agent via intravenous infusion once every 3-weeks

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities(DLTs) within 28 days (first cycle)
The DLT for this study will be evaluated in the first cycle. The DLT will include any of the following adverse events that cannot be clearly attributed to other reasons and are judged to be related to BC3402. Hematologic toxicity in the following cases: Hematologic toxicity ≥ grade 4 occurred in the first cycle, which could not be recovered to baseline value within 21 days after the occurrence, and bone marrow primordial cells<5%. Non hematologic toxicities: Grade 2 above ALT and/or AST elevational concomitant grade 2 total bilirubin elevation(non biliary obstruction or other reasons); QTcF interval > 470 ms or longer than baseline > 60 ms; Grade 3 or above non-haematological toxicity; Others Any ongoing toxicity (of any grade) not caused by disease progression that results in a delay of more than 2 weeks in the next scheduled cycle;

Secondary Outcome Measures

Full Information

First Posted
January 10, 2023
Last Updated
July 21, 2023
Sponsor
Biocity Biopharmaceutics Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05690425
Brief Title
A Phase I Study of BC3402 as a Single Agent in Patients With MDS and CMML
Official Title
A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BC3402 as a Single Agent in Patients With Myelodysplastic Syndrome SYNDR(MDS) and Chronic Myelomonocytic Leukemia(CMML)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2023 (Actual)
Primary Completion Date
March 15, 2024 (Anticipated)
Study Completion Date
June 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biocity Biopharmaceutics 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
This is a phase I study to evaluate the safety ,Tolerability, PK, PD, and preliminary efficacy of BC3402 Monotherapy in MDS or CMML, and explore the RP2D/MTD dose. The patients with very low,low,intermediate,or high,very high risk of MDS or CMML,who meet the criteria will receive BC3402 as a single agent via intravenous infusion Q3W , Up to 3 dose cohorts will be sequentially enrolled using an accelerated titration combined with a "3+3 design" approach.Dose limiting toxicities (DLT) will be assessed during the first cycles (i.e., total 3 weeks). A Safety Monitoring Committee (SMC), comprised of the Sponsor's medical representatives, safety physician, and the principal investigator (PI), will be established for the determination of dose levels to be administered and dose regimen during dose escalation based on the data available from the previous dose levels. Additional dose levels may be explored based on the emerging safety, PK, and PD data during the study.
Detailed Description
This is a phase I study to evaluate the safety ,Tolerability, PK, PD, and preliminary efficacy of BC3402 Monotherapy in MDS or CMML, and explore the RP2D/MTD dose. The patients with very low,low,intermediate,or high,very high risk of MDS or CMML,who meet the criteria will receive BC3402 as a single agent via intravenous infusion Q3W , Up to 3 dose cohorts will be sequentially enrolled using an accelerated titration combined with a "3+3 design" approach.Dose limiting toxicities (DLT) will be assessed during the first cycles (i.e., total 3 weeks). The Cohort1 will be enrolled 1 patient initially.If this subject experience any Grade 2 or higher toxicity during the first cycle, unless definitely unrelated to BC3402,2 more patients will be accrued,and the standard "3+3" dose escalation algorithm will be followed thereafter , with each cohort enrolling 3 to 6 subjects. Cohorts 2 and 3 will follow the traditional 3+3 dose escalation design. Dose limiting toxicities will be assessed during the first cycle(i.e., total21 days). If ≥ 2 subjects experience a DLT at a given dose level, the MTD would have been exceeded, further dose escalation is not pursued, and the prior dose level is expanded to six patients; if there is no more than one patient who experiences a DLT among those six patients, that dose level is considered the MTD. A Safety Monitoring Committee (SMC), comprised of the Sponsor's medical representatives, safety physician, and the principal investigator (PI), will be established for the determination of dose levels to be administered and dose regimen during dose escalation based on the data available from the previous dose levels. Additional dose levels may be explored based on the emerging safety, PK, and PD data during the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancy
Keywords
MDS and CMML

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
BC3402 treatment group
Arm Type
Experimental
Arm Description
BC3402 as a single agent via intravenous infusion once every 3-weeks
Intervention Type
Drug
Intervention Name(s)
BC3402 Injection
Other Intervention Name(s)
not have
Intervention Description
Subjects will receive BC3402 as a single agent via intravenous infusion once every 3-weeks (Q3W),the dose of BC3402 was calculated according to the dose group and body weight of the subjects.
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities(DLTs) within 28 days (first cycle)
Description
The DLT for this study will be evaluated in the first cycle. The DLT will include any of the following adverse events that cannot be clearly attributed to other reasons and are judged to be related to BC3402. Hematologic toxicity in the following cases: Hematologic toxicity ≥ grade 4 occurred in the first cycle, which could not be recovered to baseline value within 21 days after the occurrence, and bone marrow primordial cells<5%. Non hematologic toxicities: Grade 2 above ALT and/or AST elevational concomitant grade 2 total bilirubin elevation(non biliary obstruction or other reasons); QTcF interval > 470 ms or longer than baseline > 60 ms; Grade 3 or above non-haematological toxicity; Others Any ongoing toxicity (of any grade) not caused by disease progression that results in a delay of more than 2 weeks in the next scheduled cycle;
Time Frame
Dose limiting toxicities (DLT) will be assessed during the first cycle (i.e., total 3 weeks).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The subject must be able to understand and voluntarily sign the informed consent form; Subjects were 18 years old or above when they signed the informed consent form; Subjects mast be willing to undergo serial bone marrow aspirate procedures on the study; Morphologically confirmed diagnosis as extremely low risk, low risk, intermediate risk, high risk, extremely high risk MDS (IPSS-R classification) or CMML according to WHO (2016) diagnostic criteria, and WBC<13* 10^9/L (allowed to receive hydroxyurea or leukocyte removal before enrollment to reduce WBC count), and: 4.1 According to IPSS-R, patients diagnosis as extremely low risk, low risk or intermediate risk MDS must meet one or more of the following criteria: Patients who are RBCs and/or platelets transfusion-dependent , must receive stable infusion 2U/month above for 3 months before the first dose; Patients who are RBCs transfusion-dependent must Erythropoiesis stimulating agents (ESAs) failure or intolerant ; Patients who are RBCs transfusion-dependent without ESA treatment mast have serum erythropoietin level >500 U/L ; MDS patients with isolated del (5q) ("5q syndrome") must have disease progression or intolerance during lenalidomide treatment; Platelet transfusion dependent patients must be treated with thrombopoietin receptor agonist (TPO-RA) for relapse/refractory or intolerance; Persistent (>3 months) neutrophil absolute count is lower than 1.5 before screening × 10^9/L; 4.2 MDS and CMML patients rated as high-risk or extremely high-risk according to IPSS-R: The monotherapy of demethylated drugs (HMA) failed (4 cycles of decitabine treatment or 6 cycles of azacytidine treatment) or was not tolerated; Not suitable for intensive treatment; CMML patients must fail or not tolerate at least one previous treatment (including but not limited to hydroxyurea treatment, HMA treatment, etc.); 5. Patient has an Eastern Cooperative Oncology Group(ecog) status between 0 and1; 6. Expected survival time > 3 months; 7. White blood cell count (WBC) ≤ 25 × 103/μL within 7 days prior to the first dose (hydroxycarbamide or leukapheresis is allowed to meet this criterion) 8. Platelet > 30 × 10^9/L before screening; 9. Adequate renal function: (2) Serum creatinine ≤ 1.5 × Upper limit of normal value (ULN), and creatinine clearance ≥ 45 mL/min; If the urine protein is qualitative ≥ 2+, the 24-hour urine protein quantity shall be less than 3.5g; 10. Adequate liver function: (3) Total serum bilirubin ≤ 1.5 × ULN (except Gilbert syndrome, this kind of subjects only meet the requirements of direct bilirubin ≤ 1.5 × ULN); (4) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; 11. When screening, serum or urine pregnancy test (for female patients with fertility) was negative; 12. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions guidelines and be willing to undergo a bone marrow aspirate and/biopsy at screening, during and at the end of therapy on this study. 13. Male and female patients with fertility must agree to use medically approved contraceptive methods throughout the study period and continue to use them until 6 months after the last treatment of BC3402. Exclusion Criteria: Suitable and willing to accept hematopoietic stem cell transplantation (allogeneic or autologous); Immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc., were used within 2 weeks before the first use of the test drug; 3. Prior treatment with immunomodulatory agents including but not limited to thymosin, interleukin-2, and interferon within 2 weeks prior to the first dose of study drugs. Patients who have used any Chinese herbal medicine or traditional Chinese medicine with anti-tumor activity within 2 weeks prior to the first dose of study drugs. Patients who received live attenuated vaccine within 4 weeks prior to the first dose of study drug. Prior treatment with an investigational drug within 4 weeks or 5 half-lives of the agent (whichever is longer) before the planned first dose of study drug. The washout period for biologic agents should be 28 days since the last dose. Prior exposure to TIM-3 targeted therapy at any time. Participants receiving chemotherapy within 14 days or 5 half lives (whichever is longer) before the first dose of study treatment; Major organ surgery or significant trauma or radiotherapy within 2 weeks before entering the study; Have received systemic glucocorticoid (prednisone>10mg/day or equivalent dose of the same drug) or other immunosuppressive drugs within 2 weeks before the first use of the study drug; Active infections or other severe infections requiring systemic antibiotics, antiviral or antifungal drugs within 2 weeks before the first administration of the study treatment. Except for those who are treated with anti infection prevention according to local guidelines or the judgment of the researcher. Known malignant tumors in progress or requiring active treatment in the past 5 years (except those diagnosed in the study). The exceptions to this exclusion criterion are as follows: basal cell carcinoma and squamous cell skin carcinoma completely resected; And completely resected carcinoma in situ of any type; Active hepatitis B or C, history of HIV infection, active syphilis; Patients with autoimmune diseases; Known uncontrolled central nervous system (CNS) involvement; Patients with history of serious cardiovascular and cerebrovascular diseases, including but not limited to, (1)Serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, Ⅱ - Ⅲ degree atrioventricular block ect. (2) During the screening period, 12 lead electrocardiogram (ECG) was measured for three times in the research center. According to the average value of the three times calculated by the QTc formula of the instrument used in the center, QTc interval> 470ms; (3) occurrence of acute coronary heart failure, acute congestive syndrome, aortic dissection, stroke or other grade 3 or above cardiovascular and cerebrovascular events within 6 months prior to the first dose of study drug (4) Patients with history of New York Heart Society (NYHA) class≥ II, or left ventricular ejection fraction (LVEF) < 50%; (5) Clinically uncontrollable hypertension 17. Mental disorders or poor compliance; 18. Patients who are being pregnant or breastfeeding. 19.Patients with other serious systemic diseases or conditions who are deemed unsuitable to participate in this clinical study at the judgement of the Investigator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
hui zeng, prof
Phone
18002201919
Email
xyzengh@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
hui zeng, prof
Organizational Affiliation
First Affiliated Hospital of Jinan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Jinan University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510630
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hui Zeng, Prof
Phone
18002201919
Email
androps2011@hotmail.com

12. IPD Sharing Statement

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A Phase I Study of BC3402 as a Single Agent in Patients With MDS and CMML

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