Trial Title:
The Efficacy and Safety of Nelarabine Injection in Patients With T-lymphoblastic Leukemia and T-lymphoblastic Lymphoma
NCT ID:
NCT06434467
Condition:
T-lymphoblastic Leukemia
T-lymphoblastic Lymphoma
Conditions: Official terms:
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, Non-Hodgkin
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nelarabine injection
Description:
Nelarabine is a prodrug of the nucleotide metabolism inhibitor deoxyguanosine analogue
9-β-arabinoguanine (ARA-G). Nelarabine undergoes catalytic transformation by adenosine
deaminase (ADA), resulting in the removal of its methoxy group and conversion into ARA-G,
Subsequently, ARA-G undergoes sequential monophosphorylation by deoxyguanosine kinase and
deoxycytosine nucleoside kinase, yielding the active compound 5'-Guanosine triphosphate
(GTP), ARA-GTP. This active compound accumulates within leukemic blast cells and binds to
deoxyribonucleic acid (DNA), effectively inhibiting DNA synthesis and ultimately leading
to cell death.
Arm group label:
Nelarabine injection
Summary:
This is a single-arm, open-label, multicenter, phase III clinical study that aims to
evaluate the efficacy and safety of Nelarabine injection in the treatment of refractory
or recurrent T-lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL) in
both children and adults. The trial includes 83 subjects, consisting of 35 adults and 48
children, and aims to evaluate the composite complete response rate (CCR) within 2
cycles, assessed by the Independent Review Committee (IRC), following treatment with
Nelarabine injection for children and adults with refractory or recurrent T-ALL and
T-LBL.
The sample size of this study is estimated according to the treatment period of 4 cycles.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The subjects voluntarily joined this study, signed an informed consent form, and had
good compliance;
- Age: ≥ 1 year old and ≤ 65 years old (if the child has no reading ability, the
child's immediate family/guardian can fully read the informed consent form, sign and
witness the informed consent process); Eastern Cooperative Oncology Group (ECOG)
performance status (PS) score: 0-2 points; Expected survival period exceeds 3
months;
- Subject population:
1. According to the revised classification criteria for myeloid tumors and acute
leukemia in 2016, morphology, immunology, cytogenetic and molecular (MICM)
classification and/or pathological and imaging diagnosis confirmed by local
laboratories as T-ALL or T-LBL stage II-IV;
2. Philadelphia chromosome negative (Ph -);
3. Difficult to treat or disease recurrence status;
4. Previously received two chemotherapy regimens without response, or experienced
recurrence after treatment.
- The main organ functions well and meets the following standards:
1. Biochemical examination must meet the following standards:
Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN) (if
T-ALL/T-LBL affects the liver, total bilirubin ≤ 3 times the upper limit of
normal value); Alanine transferase (ALT) and aspartate transferase (AST) ≤ 3 ×
ULN (if T-ALL/T-LBL affects the liver, ALT and/or AST ≤ 5 × ULN);
Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance rate estimated based
on Cockcroft Gault glomerular filtration formula ≥ 50 mL/min.
2. The coagulation function test needs to meet the following standards:
prothrombin time (PT), activated partial thromboplastin time (APTT),
international standardized ratio (INR) ≤ 1.5 x ULN (without receiving
anticoagulant treatment).
- Before starting to use the investigational drug, all non hematological toxicity
(except for hair loss and fatigue) of previous anti leukemia treatments must have
been restored to level 1 or baseline levels ((NCI Common Terminology Criteria for
Adverse Events(CTCAE) version5.0));
- Female participants 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; Within 7 days prior to enrollment,
the serum pregnancy test was negative and must be a non lactating subject; Male
participants should agree to adopt avoidance measures during the study period and
within 6 months after the end of the study period.
Exclusion Criteria:
- Previous treatment:
1. Within 3 weeks prior to the first medication, chemotherapy (including
intrathecal injection, excluding ALL/LBL maintenance therapy) was received.
Within 12 weeks prior to the first medication, radiation therapy (brain spine,
pelvis, and other radiation areas exceeding 25% of the total bone marrow
volume), immune checkpoint inhibitors, Chimeric Antigen Receptor T-Cell (CAR-T)
Therapy were received. Other small molecule anti-tumor treatments received
before the first medication (washout period calculated from the end of the last
treatment) were within 5 half-lives;
2. Within 7 days prior to the first administration, receive ≥ 5 days of
intravenous or oral prednisone ≥ 30mg/m2 or an equal amount of other
glucocorticoids. Within 28 days prior to the first administration, receive ≥ 14
days of intravenous or oral prednisone ≥ 30mg/m2 or an equal amount of other
glucocorticoids. Single dose prevention or treatment of airway stenosis is
allowed to be used; Note: If the patient's white blood cell (WBC) is ≥ 30 ×
10^9/L, or if the liver, spleen, or lymph nodes are significantly enlarged;
Patients with tumor lysis characteristics (biochemical tests, etc.) may undergo
pre-treatment, and the use of prednisone/dexamethasone ± cyclophosphamide
during the pre-treatment period is allowed to prevent tumor lysis syndrome;
3. Vaccination received within 4 weeks prior to the first medication, or planned
vaccination during the study period;
4. Participated in clinical trials of other anti-tumor drugs within 4 weeks prior
to the first medication use;
5. According to the researcher's judgment, there are individuals with accompanying
diseases that seriously endanger the safety of the subjects or affect the
completion of the study, or individuals who are deemed unsuitable for
enrollment due to other reasons.
- Concomitant diseases and medical history:
1. Has experienced or currently suffers from other malignant tumors within 3 years
prior to the first medication use. The following two situations can be included
in the study: achieving disease-free survival (DFS) for 5 consecutive years for
other malignant tumors treated with a single surgery; Cured cervical cancer in
situ, thyroid cancer, non melanoma skin cancer, and superficial bladder tumors
[Ta (non invasive tumor), Ti (carcinoma in situ), and T1 (tumor infiltrating
basement membrane)];
2. Unresolved neurotoxicity of ≥ CTC AE II grade due to any previous treatment;
3. Within 28 days prior to the start of the research treatment, significant
surgical treatment, open biopsy, and obvious traumatic injury were received;
4. Within 3 months prior to the first medication, there have been incidents of
arterial/venous thrombosis, such as cerebrovascular accidents (including
cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary
embolism;
5. Individuals with a history of psychiatric drug abuse who are unable to quit or
have mental disorders;
6. Within 6 months prior to the first medication, the patient had ≥ grade 2
myocardial ischemia or infarction, arrhythmia (QTcF>450ms in males and>470ms in
females), ≥ grade 2 congestive heart failure (NYHA classification), and left
ventricular ejection fraction (LVEF) assessed by echocardiography<50%.
7. Existence of active infection (≥ CTC AE level 2 infection);
8. Active hepatitis *; Hepatitis B reference: hepatitis B virus (HBV) DNA
detection value ≥ upper limit of normal value; Hepatitis C reference: hepatitis
C virus (HCV) antibody positive, and HCV virus titer detection value exceeds
the upper limit of normal value;
9. Individuals with a history of immunodeficiency, including HIV positivity or
other acquired or congenital immunodeficiency diseases, or a history of organ
transplantation;
10. Have a history of epilepsy;
11. Have a history of Down syndrome;
12. Merge central nervous system leukemia/lymphoma.
- The patient plans to receive chest radiation therapy.
Gender:
All
Minimum age:
1 Year
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Anhui Provincial Hospital
Address:
City:
Hefei
Zip:
230000
Country:
China
Contact:
Last name:
Xiaoyu Zhu, Doctor
Phone:
15255456091
Email:
xiaoyuz@ustc.edu.cn
Facility:
Name:
Aerospace Medical Center
Address:
City:
Beijing
Zip:
100049
Country:
China
Contact:
Last name:
Jingbo Wang, Doctor
Phone:
13693587668
Email:
dpwangjingbo@vip.sina.com
Facility:
Name:
Beijing Tongren Hospital,CMU
Address:
City:
Beijing
Zip:
100730
Country:
China
Contact:
Last name:
Dongsheng Huang, Doctor
Phone:
13601113102
Email:
hds5180@sina.com
Facility:
Name:
Children's Hospital of Chongqing Medical University
Address:
City:
Chongqing
Zip:
400010
Country:
China
Contact:
Last name:
Jie Yu, Doctor
Phone:
13983762652
Email:
1808106657@qq.com
Facility:
Name:
The Second Affiliated Hospital of Army Military Medical University
Address:
City:
Chongqing
Zip:
400037
Country:
China
Facility:
Name:
The first hospital of Lanzhou University
Address:
City:
Lanzhou
Zip:
730000
Country:
China
Contact:
Last name:
Zijian Li, Doctor
Phone:
18993115461
Email:
ldyy_lizj@lzu.edu.cn
Facility:
Name:
Sun Yat-sen University Cancer Prevention Center
Address:
City:
Guangzhou
Zip:
510062
Country:
China
Contact:
Last name:
Yizhuo Zhang, Doctor
Phone:
18819241079
Email:
zhangyzh@sysucc.org.cn
Facility:
Name:
Cancer Hospital Affiliated to Guangxi Medical University
Address:
City:
Nanning
Zip:
530021
Country:
China
Contact:
Last name:
Hong Cen, Doctor
Phone:
13507711671
Email:
cen_hong@163.com
Facility:
Name:
First Affiliated Hospital of Guangxi Medical University
Address:
City:
Nanning
Zip:
530021
Country:
China
Contact:
Last name:
Yunyan He, Doctor
Phone:
13607868275
Email:
yunyanhe@aliyun.com
Facility:
Name:
Yulin Red Cross Hospital
Address:
City:
Yulin
Zip:
537000
Country:
China
Contact:
Last name:
Zhao Lv, Bachelor
Phone:
15277931749
Email:
371535062@qq.com
Facility:
Name:
Affiliated Hospital of Zunyi Medical University
Address:
City:
Zunyi
Zip:
563000
Country:
China
Contact:
Last name:
Yan Chen, Doctor
Phone:
13985261758
Email:
cyz600@163.com
Facility:
Name:
The second Hospital of Hebei Medical University
Address:
City:
Shijiazhuang
Zip:
50004
Country:
China
Contact:
Last name:
Jingyu Zhang, Doctor
Phone:
18032227288
Email:
zhangjy69@163.com
Facility:
Name:
Xingtai People's Hospital
Address:
City:
Xingtai
Zip:
54001
Country:
China
Contact:
Last name:
Zongjiu Jiao, Doctor
Phone:
18631921299
Email:
1449569258@qq.com
Facility:
Name:
Affiliated cancer hospital of harbin medical university
Address:
City:
Harbin
Zip:
150001
Country:
China
Contact:
Last name:
Aichun Liu, Doctor
Phone:
13633611958
Email:
aichun2002@hotmail.com
Facility:
Name:
Institute of Hematology & Oncology, Harbin First Hospital
Address:
City:
Harbin
Zip:
150010
Country:
China
Contact:
Last name:
Jun Ma, Doctor
Phone:
13304518000
Email:
majun0322@126.com
Facility:
Name:
Henan Children's Hospital
Address:
City:
Zhengzhou
Zip:
450018
Country:
China
Contact:
Last name:
Wei Liu, Doctor
Phone:
13673710016
Email:
liuweixinxiang@163.com
Facility:
Name:
Tongji Medical College of HUST
Address:
City:
Wuhan
Zip:
430030
Country:
China
Contact:
Last name:
Aiguo Liu, Doctor
Phone:
13807196944
Email:
drliuaiguo@163.com
Facility:
Name:
Hunan Children's Hospital
Address:
City:
Changsha
Zip:
410007
Country:
China
Contact:
Last name:
Mincui Zheng, Master
Phone:
13908467333
Email:
13908467333@163.com
Facility:
Name:
Nanjing childrens Hospital
Address:
City:
Nanjing
Zip:
210008
Country:
China
Contact:
Last name:
Yongjun Fang, Doctor
Phone:
18951769586
Email:
fyj322@189.cn
Facility:
Name:
Jiangsu Provincial People's Hospital
Address:
City:
Nanjing
Zip:
210029
Country:
China
Contact:
Last name:
Yu Zhu, Doctor
Phone:
13851435363
Email:
zhuyu@jsph.org.cn
Facility:
Name:
The First Hospital Of Jilin University
Address:
City:
Changchun
Zip:
130000
Country:
China
Contact:
Last name:
Yehui Tan, Doctor
Phone:
15804302605
Email:
276769165@qq.com
Facility:
Name:
Weihai Municipal Hospital
Address:
City:
Weihai
Zip:
264200
Country:
China
Contact:
Last name:
Jie Yu, Doctor
Phone:
13869058479
Email:
yujiejessica@126.com
Facility:
Name:
Huashan Hospital Fudan University
Address:
City:
Shanghai
Zip:
200040
Country:
China
Contact:
Last name:
Xiaoqin Wang, Doctor
Phone:
13621851543
Email:
wangxiaoqin@shmu.edu.cn
Facility:
Name:
Children's Hospital of Fudan University
Address:
City:
Shanghai
Zip:
201102
Country:
China
Contact:
Last name:
Xiaowen Zhai, Doctor
Phone:
18017590808
Email:
zhaixiaowendy@163.com
Facility:
Name:
Shanxi Provincial People's Hospital
Address:
City:
Xi'an
Zip:
710068
Country:
China
Contact:
Last name:
Yi Wang, Doctor
Phone:
13571936193
Email:
13571936193@163.com
Facility:
Name:
Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital
Address:
City:
Chengdu
Zip:
610072
Country:
China
Contact:
Last name:
Xiaobing Huang, Doctor
Phone:
18981838236
Email:
huangxiaobing@med.uestc.edu.cn
Facility:
Name:
Tianjin Cancer Hospital
Address:
City:
Tianjin
Zip:
300202
Country:
China
Contact:
Last name:
Yafei Wang, Doctor
Phone:
18622221250
Email:
Drwang2005@163.com
Facility:
Name:
First Affiliated Hospital of Xinjiang Medical University
Address:
City:
Urumqi
Zip:
830000
Country:
China
Contact:
Last name:
Xinhong Guo, Doctor
Phone:
15292898288
Email:
guoxinhong222@sina.cn
Facility:
Name:
The First Affiliated Hospital of Kunming Medical University
Address:
City:
Kunming
Zip:
650000
Country:
China
Contact:
Last name:
Mingxia Shi, Doctor
Phone:
13888060581
Email:
Shmxia2002@sina.com
Facility:
Name:
Children's Hospital of Zhejiang University School of Medicine
Address:
City:
Hangzhou
Zip:
310000
Country:
China
Contact:
Last name:
Xiaojun Xu, Doctor
Phone:
13858067554
Email:
xuxiaojun@zju.edu.cn
Start date:
May 2024
Completion date:
May 2026
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/NCT06434467
