Trial Title:
Clinical Trial Evaluating the Safety of the TQB2928 Injection Combination Therapy
NCT ID:
NCT06008405
Condition:
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Conditions: Official terms:
Myelodysplastic Syndromes
Azacitidine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
TQB2928 Injection + Azacitidine for injection
Description:
TQB2928 injection is a fully humanized Immunoglobulin G 4 (IgG4) subtype monoclonal
antibody targeting CD47.
Azacitidine for injection is a nucleoside metabolism inhibitor that inhibits
DeoxyriboNucleic Acid (DNA) methyltransferase, reduces DNA methylation and alters gene
expression.
Arm group label:
TQB2928 Injection + Azacitidine for injection
Summary:
This study carried out a phase Ib clinical trial of TQB2928 injection combined therapy in
patients with hematological malignancies, to explore the safety, pharmacokinetics,
pharmacodynamics and preliminary efficacy of TQB2928 injection combined with azacitidine
for injection in Acute Myeloid Leukemia (AML)/Myelodysplastic Syndromes (MDS) subjects.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Subjects voluntarily join this study, sign the informed consent form, and have good
compliance;
- Age: age ≥ 18 years old (when signing the informed consent); Eastern Cooperative
Oncology Group Performance Status (ECOG PS) score: 0-2 points; expected survival
time of more than 3 months;
- Subject population:
1. The subjects were diagnosed with AML or MDS according to the World Health
Organization (WHO) 2016 revised classification criteria for hematopoietic and
lymphoid tissue tumors.
2. MDS adopts the revised International Prognostic Scoring System (IPSS-R) > 3.5
(higher risk group), and the proportion of bone marrow blasts ≥ 5%.
3. Phase 1 (dose escalation phase) and Phase 2 (dose expansion phase) enrollment
1. Untreated AML who cannot tolerate standard induction chemotherapy;
2. Untreated higher-risk MDS;
- The main organs function well.
- Subjects must be willing to provide available diagnostic evidence or perform bone
marrow aspiration and biopsy before the study treatment and must be willing to
perform bone marrow aspiration and biopsy after receiving the study treatment.
- Female subjects of childbearing age should agree to use contraceptive measures (such
as intrauterine devices, contraceptives or condoms) during the study period and
within 6 months after the end of the study; negative serum pregnancy test within 7
days before study enrollment, and must be non-lactating subjects; male subjects
should agree to use contraceptive measures during the study period and within 6
months after the end of the study period.
Exclusion Criteria:
- Tumor disease and medical history:
1. central nervous system leukemia;
2. Other malignant tumors have occurred or are currently suffering from other
malignant tumors within 3 years. The following two conditions can be included:
other malignancies treated by a single surgery, achieving 5 years of continuous
disease-free survival (DFS);
3. Clinically significant uncontrolled pleural effusion, ascites, moderate or more
remarkable pericardial effusion requiring repeated drainage.
- Previous anti-tumor therapy:
1. Previous use of other drugs targeting the CD47/signal-regulatory protein α
(SIRPα) signaling pathway;
2. Received any antibody drug treatment under investigation within 4 weeks before
the first administration, received Chimeric Antigen Receptor -T (CAR-T)
therapy, or other immune cell therapy, or autologous hematopoietic stem cell
transplantation 3 months before the first administration;
3. Previously received allogeneic hematopoietic stem cell transplantation;
4. Received any major surgery, chemotherapy and/or radiotherapy, immunotherapy or
targeted therapy within 4 weeks before the first administration;
5. The first administration is less than 5 drug half-lives from the previous oral
targeted therapy (calculated from the end of the last treatment);
6. Received Chinese patent medicines with anti-tumor indications within 2 weeks
before the first administration, including compound mylabris capsules, Kangai
injection, Kanglaite capsule/injection, Aidi injection, javanica oil, Xiao'ai
ping tablet/injection, cinobufagin capsule, etc., (using symptomatic treatment
such as hydroxyurea, leukocyte apheresis and erythropoietin and other
hematopoietic growth factors within 7 days is allowed);
- Combined diseases and medical history:
1. Liver abnormalities:
1. Decompensated cirrhosis (Child-Pugh liver function grade B or C);
2. Hepatitis B virus infection;
3. Hepatitis C virus infection;
2. Kidney abnormalities:
1. Renal failure requires hemodialysis or peritoneal dialysis;
2. history of nephrotic syndrome.
3. Gastrointestinal abnormalities:
1. Persistent chronic diarrhea despite maximal medical treatment;
2. Active inflammatory bowel disease (such as ulcerative colitis, Crohn's
disease) within 4 weeks before the first dose.
4. Cardiovascular and cerebrovascular abnormalities:
1. Concomitant or previous history of central nervous system disease,
including seizures, hemorrhagic/ischemic stroke, severe brain injury,
dementia, Parkinson's disease, cerebellar disease, paralysis, aphasia,
mental illness, disturbance of consciousness, unknown Cause coma,
neuropathy, organic brain syndrome, etc.;
2. Brain Magnetic Resonance Imaging (MRI) evidence of inflammatory lesions
and/or vasculitis;
3. Cerebrovascular accident, cerebral infarction, etc., occurred within 6
months before the first administration;
4. Arterial/venous thrombosis events such as deep vein thrombosis and
pulmonary embolism occurred within 6 months before the first
administration;
5. Accompanying or previous history of cardiovascular disease, including
grade III or IV heart failure defined by the New York Heart Association
classification, atrioventricular block of grade II and above, myocardial
infarction within 6 months before the first dose, severe History of
arrhythmia, unstable angina, etc.;
6. Hypertension that cannot be controlled by the combination of two drugs (at
least 2 measurements are systolic blood pressure ≥ 160 mmHg, diastolic
blood pressure ≥ 100 mmHg);
7. Previously or currently suffering from heart valvulitis and endarteritis.
5. History of immunodeficiency:
1. Known human immunodeficiency virus (HIV) infection or other acquired or
congenital immunodeficiency diseases;
2. Prepare to undergo or have previously received organ transplantation or
have noticeable host transplantation reactions;
3. Need to receive systemic immunosuppressant therapy, including but not
limited to the use of cyclosporine, tacrolimus, etc., within 4 weeks
before the first administration, and receive high-dose glucocorticoid
therapy (prednisone >30 mg /day or other glucocorticoids at equivalent
doses), or those with autoimmune diseases, allergic diseases or immune
rejection receiving any other immunosuppressive therapy. Patients
receiving inhaled or topical corticosteroids or prednisone < 10 mg/day or
equivalent doses of other systemic corticosteroids at a stable dose for at
least 4 weeks before the first dose or receiving Prophylactic medication
to prevent infusion reactions can be selected.
6. Uncontrolled active systemic bacterial, fungal, or viral infection.
7. Unexplained fever > 38.5 ℃ occurred during screening or before the first
medication (except for fever caused by tumors judged by the investigator).
8. Subjects with any history of hemolytic anemia (including Evans syndrome) or
positive Coombs test within 3 months before the first administration.
9. Lung disease:
1. Blood oxygen saturation ≤ 95% at rest;
2. Previous or current noninfectious pneumonia requiring corticosteroid
therapy (including but not limited to acute respiratory distress syndrome,
acute hypersensitivity pneumonia, drug-associated pneumonia, bronchospasm,
acute interstitial pneumonia, idiopathic pulmonary interstitial fibrosis,
etc.);
3. Evidence of active pneumonia found on chest Computed Tomography (CT) scan
during the screening period;
4. Active tuberculosis.
10. A history of severe allergies of unknown causes; known allergies to monoclonal
antibody drugs or exogenous human immunoglobulins; known allergies to study
drug excipients.
11. Combined with serious or not well-controlled concomitant diseases that,
according to the investigator's judgment, seriously endanger the subject's
safety or affect the study's completion.
12. With or previous history of pituitary or adrenal dysfunction (as assessed by
the investigator).
13. History of drug abuse or drug abuse.
14. myelodysplastic syndromes (MDS) subjects combined with the following two
conditions: uncorrected folic acid and vitamin B12 deficiency MDS transformed
from pre-existing myeloproliferative neoplasms (MPN) or MDS/MPN types that meet
the World Health Organization (WHO) 2016 classification criteria, including
chronic Myeloid leukemia (CMML), atypical chronic myeloid leukemia (CML),
juvenile myeloid leukemia (JMML).
15. M3 type acute myeloid leukemia (AML) and AML with positive BCR-ABL mutation
gene.
- Inoculation within 4 weeks before the first administration or vaccination with live
attenuated vaccine during the planned study period.
- Participated in other drug clinical trials within the past 30 days.
- It is estimated that the compliance of patients participating in this clinical
research needs to be improved.
- Hypersensitivity to azacitidine or mannitol;
Gender:
All
Minimum age:
18 Years
Maximum age:
90 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking University People's Hospital
Address:
City:
Beijing
Zip:
100044
Country:
China
Status:
Recruiting
Contact:
Last name:
Hao Jiang, Doctor
Phone:
+86 13601164350
Email:
Jiangha0090@sina.com
Facility:
Name:
Chongqing Hospital of Traditional Chinese Medicine
Address:
City:
Chongqing
Zip:
400011
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Weiqi Nian, Doctor
Phone:
13883652913
Email:
nwqone@126.com
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Zip:
450003
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xudong Wei, Doctor
Phone:
+86 13837169301
Email:
weixudong63@126.com
Facility:
Name:
The Third Xiangya Hospital of Central South University
Address:
City:
Changsha
Zip:
410013
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ying Li, Doctor
Phone:
+86 13607499962
Email:
13538563@qq.com
Facility:
Name:
The First Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Zip:
330006
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Fei Li, Doctor
Phone:
+86 13970038386
Email:
lifeigcp2022@163.com
Facility:
Name:
The First Hospital of Jilin University
Address:
City:
Changchun
Zip:
130021
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Sujun Gao, Doctor
Phone:
+86 15843073208
Email:
sujung1963@qq.com
Facility:
Name:
The First Affiliated Hospital of China Medical University
Address:
City:
Shenyang
Zip:
110000
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiaojing Yan, Doctor
Phone:
+86 13889128302.
Email:
13538563@qq.com
Facility:
Name:
Shanghai Jiaotong University, School of Medicine, Ruijin Hospital
Address:
City:
Shanghai
Zip:
200025
Country:
China
Status:
Recruiting
Contact:
Last name:
Weili Zhao, Doctor
Phone:
+862164150275
Email:
zwl_trail@163.com
Facility:
Name:
The First Affiliated Hospital Zhejiang University School of Medicine
Address:
City:
Hangzhou
Zip:
310006
Country:
China
Status:
Recruiting
Contact:
Last name:
Hongyan Tong, Doctor
Phone:
+8618120165251
Email:
tonghongyan@zju.edu.cn
Start date:
September 2023
Completion date:
May 2025
Lead sponsor:
Agency:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Agency class:
Industry
Source:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06008405
