The Efficacy and Safety of Nelarabine Injection in Patients With T-lymphoblastic Leukemia and T-lymphoblastic Lymphoma

NCT06434467 | Not Yet Recruiting Phase 3

• 1 other identifier: NLB-III-01
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 30

Brief 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.

Conditions

T-lymphoblastic Leukemia; T-lymphoblastic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Composite complete response rate (CCR) assessed by the Independent Review Committee (IRC)

  Proportion of complete responses (CCR) after 2 cycles of antineoplastic therapy as determined by independent review committee (IRC) assessment

  During the study period (Baseline up to two months)

Secondary Outcomes (11)

• Composite complete response rate (CCR) assessed by the investigator

  During the study period (Baseline up to two months)

• Objective Remission Rate (ORR)

  During the study period (Baseline up to two months)

• Duration of complete remission (DOCR)

  During the study period (Baseline up to two years)

• Disease-free survival (DFS)

  During the study period (Baseline up to two years)

• Overall survival (OS)

  During the study period (Baseline up to two years)

Study Arms (1)

Nelarabine injection

EXPERIMENTAL

Adults (≥18 years old): 1500 mg/m², administer intravenously for at least 2 hours on days 1, 3, and 5, repeating every 21 days. Children (1-17 years old): 650 mg/m ², administer intravenously for 1 hour daily for 5 consecutive days, repeating every 21 days.

Drug: Nelarabine injection

Interventions

Nelarabine injection DRUG

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.

Nelarabine injection

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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;
• Philadelphia chromosome negative (Ph -);
• Difficult to treat or disease recurrence status;
• Previously received two chemotherapy regimens without response, or experienced recurrence after treatment.
• The main organ functions well and meets the following standards:
• 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.
• 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.

You may not qualify if:

• Previous treatment:
• 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;
• 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;
• Vaccination received within 4 weeks prior to the first medication, or planned vaccination during the study period;
• Participated in clinical trials of other anti-tumor drugs within 4 weeks prior to the first medication use;
• 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:
• 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 \[Ta (non invasive tumor), Ti (carcinoma in situ), and T1 (tumor infiltrating basement membrane)\];
• Unresolved neurotoxicity of ≥ CTC AE II grade due to any previous treatment;
• Within 28 days prior to the start of the research treatment, significant surgical treatment, open biopsy, and obvious traumatic injury were received;
• 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;
• Individuals with a history of psychiatric drug abuse who are unable to quit or have mental disorders;
• 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%.
• Existence of active infection (≥ CTC AE level 2 infection);
• 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;

Sponsors & Collaborators

• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: lead

Study Sites (30)

Anhui Provincial Hospital

Hefei, Anhui, 230000, China

Location

Aerospace Medical Center

Beijing, Beijing Municipality, 100049, China

Location

Beijing Tongren Hospital,CMU

Beijing, Beijing Municipality, 100730, China

Location

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400010, China

Location

The Second Affiliated Hospital of Army Military Medical University

Chongqing, Chongqing Municipality, 400037, China

Location

The first hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

Location

Sun Yat-sen University Cancer Prevention Center

Guangzhou, Guangdong, 510062, China

Location

Cancer Hospital Affiliated to Guangxi Medical University

Nanning, Guangxi, 530021, China

Location

First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530021, China

Location

Yulin Red Cross Hospital

Yulin, Guangxi, 537000, China

Location

Affiliated Hospital of Zunyi Medical University

Zunyi, Guizhou, 563000, China

Location

The second Hospital of Hebei Medical University

Shijiazhuang, Hebei, 50004, China

Location

Xingtai People's Hospital

Xingtai, Hebei, 54001, China

Location

Affiliated cancer hospital of harbin medical university

Harbin, Heilongjiang, 150001, China

Location

Institute of Hematology & Oncology, Harbin First Hospital

Harbin, Heilongjiang, 150010, China

Location

Henan Children's Hospital

Zhengzhou, Henan, 450018, China

Location

Tongji Medical College of HUST

Wuhan, Hubei, 430030, China

Location

Hunan Children's Hospital

Changsha, Hunan, 410007, China

Location

Nanjing childrens Hospital

Nanjing, Jiangsu, 210008, China

Location

Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, 210029, China

Location

The First Hospital Of Jilin University

Changchun, Jilin, 130000, China

Location

Weihai Municipal Hospital

Weihai, Shandong, 264200, China

Location

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

Shanxi Provincial People's Hospital

Xi’an, Shanxi, 710068, China

Location

Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610072, China

Location

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, 300202, China

Location

First Affiliated Hospital of Xinjiang Medical University

Ürümqi, Xinjiang, 830000, China

Location

The First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650000, China

Location

Children's Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

nelarabine

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Jun Ma, Doctor

CONTACT

13304518000; majun0322@126.com

Yizhuo Zhang, Doctor

CONTACT

18819241079; zhangyzh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2024
• First Posted: May 30, 2024
• Study Start: May 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: May 1, 2026
• Last Updated: May 30, 2024

Record last verified: 2023-11

Locations

CN (30)