Clinical trial NCT06434467: The Efficacy and Safety of Nelarabine Injection in Patients With T-lymphoblastic Leukemia and T-lymphoblastic Lymphoma
Official title: 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 Children and Adults
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: T-lymphoblastic Leukemia
T-lymphoblastic Lymphoma
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-05-30
Enrollment: 83
Sex: ALL
Minimum age (years): 1
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Composite complete response rate (CCR) assessed by the Independent Review Committee (IRC)
timeFrame: During the study period (Baseline up to two months)
Secondary outcomes:
measure: Composite complete response rate (CCR) assessed by the investigator
timeFrame: During the study period (Baseline up to two months)
measure: Objective Remission Rate (ORR)
timeFrame: During the study period (Baseline up to two months)
measure: Duration of complete remission (DOCR)
timeFrame: During the study period (Baseline up to two years)
measure: Disease-free survival (DFS)
timeFrame: During the study period (Baseline up to two years)
measure: Overall survival (OS)
timeFrame: During the study period (Baseline up to two years)
measure: Incidence of adverse events (AEs)
timeFrame: During the study period (Baseline up to two years)
measure: Incidence of serious adverse events (SAEs)
timeFrame: During the study period (Baseline up to two years)
measure: Peak time (Tmax)
timeFrame: During the study period (Baseline up to two years)
measure: Peak concentration(Cmax)
timeFrame: During the study period (Baseline up to two years)
measure: Half-life(t1/2)
timeFrame: During the study period (Baseline up to two years)
measure: Negative rate of minimal residual disease in bone marrow (MRD)
timeFrame: During the study period （Baseline up to two years)
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: Aerospace Medical Center
state: Beijing
city: Beijing
country: China
facility: Beijing Tongren Hospital,CMU
state: Beijing
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Army Military Medical University
state: Chongqing
city: Lanzhou
country: China
facility: The first hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Prevention Center
state: Guangdong
city: Nanning
country: China
facility: Cancer Hospital Affiliated to Guangxi Medical University
state: Guangxi
city: Nanning
country: China
facility: First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Yulin
country: China
facility: Yulin Red Cross Hospital
state: Guangxi
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Shijiazhuang
country: China
facility: The second Hospital of Hebei Medical University
state: Hebei
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
city: Harbin
country: China
facility: Affiliated cancer hospital of harbin medical university
state: Heilongjiang
city: Harbin
country: China
facility: Institute of Hematology & Oncology, Harbin First Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Children's Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Medical College of HUST
state: Hubei
city: Changsha
country: China
facility: Hunan Children's Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing childrens Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital Of Jilin University
state: Jilin
city: Weihai
country: China
facility: Weihai Municipal Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
city: Xi'an
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Urumqi
country: China
facility: First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: The First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: Children's Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: