Trial Title:
A Phase I Study of BC3402 as a Single Agent in Patients With MDS and CMML
NCT ID:
NCT05690425
Condition:
Hematologic Malignancy
Conditions: Official terms:
Hematologic Neoplasms
Conditions: Keywords:
MDS and CMML
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BC3402 Injection
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.
Arm group label:
BC3402 treatment group
Other name:
not have
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The subject must be able to understand and voluntarily sign the informed consent
form;
2. Subjects were 18 years old or above when they signed the informed consent form;
3. Subjects mast be willing to undergo serial bone marrow aspirate procedures on the
study;
4. 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:
1. Patients who are RBCs and/or platelets transfusion-dependent , must receive stable
infusion 2U/month above for 3 months before the first dose;
2. Patients who are RBCs transfusion-dependent must Erythropoiesis stimulating agents
(ESAs) failure or intolerant ;
3. Patients who are RBCs transfusion-dependent without ESA treatment mast have serum
erythropoietin level >500 U/L ;
4. MDS patients with isolated del (5q) ("5q syndrome") must have disease progression or
intolerance during lenalidomide treatment;
5. Platelet transfusion dependent patients must be treated with thrombopoietin receptor
agonist (TPO-RA) for relapse/refractory or intolerance;
6. 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:
1. The monotherapy of demethylated drugs (HMA) failed (4 cycles of decitabine treatment
or 6 cycles of azacytidine treatment) or was not tolerated;
2. Not suitable for intensive treatment;
3. 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:
1. Suitable and willing to accept hematopoietic stem cell transplantation (allogeneic
or autologous);
2. 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.
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.
4. 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.
5. Patients who received live attenuated vaccine within 4 weeks prior to the first dose
of study drug.
6. 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.
7. Prior exposure to TIM-3 targeted therapy at any time.
8. Participants receiving chemotherapy within 14 days or 5 half lives (whichever is
longer) before the first dose of study treatment;
9. Major organ surgery or significant trauma or radiotherapy within 2 weeks before
entering the study;
10. 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;
11. 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.
12. 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;
13. Active hepatitis B or C, history of HIV infection, active syphilis;
14. Patients with autoimmune diseases;
15. Known uncontrolled central nervous system (CNS) involvement;
16. 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of Jinan University
Address:
City:
Guangzhou
Zip:
510630
Country:
China
Status:
Recruiting
Contact:
Last name:
Hui Zeng, Prof
Phone:
18002201919
Email:
androps2011@hotmail.com
Start date:
July 6, 2023
Completion date:
June 15, 2024
Lead sponsor:
Agency:
Biocity Biopharmaceutics Co., Ltd.
Agency class:
Industry
Source:
Biocity Biopharmaceutics Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05690425
