Phase II Study of QLC2519 in Pediatric Solid Tumor Participants

Official title

A Multicenter, Open-label Phase II Clinical Study Evaluating the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Albipagrastim Alfa for Injection (QLC2519) in Pediatric Solid Tumor Participants

Overview

QLC2519 (Mai Li Sheng®) is a new protein drug created by fusing the N-terminal of highly active modified G-CSF with the C-terminal of HSA. The modified G-CSF retained high activity while reducing affinity for the G-CSF receptor, which can significantly inhibit the the G-CSF receptor-mediated (RMC) pathway. The aim of this study is to evaluate the PK/PD characteristics of QLC2519 in preventing chemotherapy-induced neutropenia (CIN) in children with sarcoma.

Detailed description

This study is a multicenter, open lable Phase II study planed to enroll 18 children with pediatric sarcoma. The participants will receive the VDC/IE chemotherapy regimen (VDC: vincristine, doxorubicin, cyclophosphamide; IE: ifosfamide, etoposide) and will be scheduled to undergo 3 chemotherapy cycles (21 days per cycle). The participants will be stratified by age (\<6 years, 6 to \<12 years, 12 to \<18 years), with enrollment progressing from the older to the younger age groups (6 in each group).

Interventions

• Drug Albipagrastim alf
  QLC2519 500 μg/kg was administered 48 hours after chemotherapy (generally on D4 of the first and third chemotherapy cycles, and on D7 of the second cycle, between 6:00 and 10:00 AM), once per chemotherapy cycle.

Primary outcome measures

• Cmax of QLC2519 [Time frame: At treatment Cycle 1 and Cycle 3 (cycle length = 21 days)]]
• AUC0-t of QLC2519 [Time frame: At treatment Cycle 1 and Cycle 3 (cycle length = 21 days)]]
• Time to start administering chemotherapy drugs until the nadir of absolute neutrophil count (ANC) [Time frame: At treatment Cycle 1 and Cycle 3 (cycle length = 21 days)]]

Secondary outcome measures (4)

• Duration and incidence of severe ANC reduction [Time frame: At treatment cycle 1 to cycle 3 (cycle length = 21 days)]
• Efficacy: Incidence of febrile neutropenia (FN) [Time frame: At treatment cycle 1 to cycle 3 (cycle length = 21 days)]
• Duration and incidence of ANC < 1.0 × 10^9/L [Time frame: At treatment cycle 1 to cycle 3 (cycle length = 21 days)]
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) [Time frame: Up to Week 14]

Eligibility criteria

Inclusion criteria

• Age 0-18 years (excluding boundary values), any gender;
• Participant diagnosed with pediatric sarcoma based on pathological histology;
• Participant was suitable for receiving the VDC/IE chemotherapy regimen, and planning to receive at least 3 chemotherapy cycles (VDC: vincristine, doxorubicin, cyclophosphamide; IE: ifosfamide, etoposide);
• ECOG ≤1;
• Expected survival ≥3 months, and expected to complete the 3 chemotherapy cycles specified in the regimen;
• Hematology, liver function, and renal function before the first administration of chemotherapy drugs meet the following requirements:
• Hematology: absolute neutrophil count (ANC) in peripheral blood ≥2.0×10\^9/L (or above the lower limit of normal); platelet count (PLT) ≥100×10\^9/L; hemoglobin (HGB) ≥90 g/L; white blood cell count (WBC) ≥4.0×10\^9/L;
• Liver function: total bilirubin (TBIL) ≤1.5×ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×ULN; for patients with liver metastasis, ALT and AST ≤2.5×ULN;
• Renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance rate (CCr) ≥60 mL/min;
• Normal bone marrow hematopoietic function, no bleeding tendency (INR <1.5);
• Female participants of potential reproductive ability (post-menarche) are neither pregnant nor breastfeeding; participants of potential reproductive ability (e.g., females post-menarche or males post-spermarche) must agree to use effective contraception from the time of signing the informed consent until at least 3 months after the last administration.

Exclusion criteria

• Tumor had metastasized to or invaded the bone marrow;
• Previously received chemotherapy or radiotherapy;
• Planned surgery or radiotherapy during the trial (excluding the follow-up period);
• Presence of other malignant tumors besides sarcoma (participants with previously cured malignant tumors with no recurrence within the past 5 years may be included in this study);
• Primary central nervous system tumor or existing central nervous system involvement, or suspected central nervous system metastasis based on clinical manifestations, deemed unsuitable for participation in this study by the investigator;
• History of primary hematologic diseases, including but not limited to leukemia, myelodysplastic syndromes, aplastic anemia, sickle cell anemia, congenital neutropenia, or cyclic neutropenia;
• Previously received or planned to undergo bone marrow transplantation, hematopoietic stem cell transplantation, or organ transplantation during the trial;
• Diseases with severe cardiac dysfunction, including but not limited to poorly controlled arrhythmia or heart failure;
• Diseases with severe pulmonary dysfunction, including but not limited to pulmonary embolism, lung abscess, or acute respiratory distress syndrome;
• Presence of splenomegaly or diseases that may cause splenomegaly (such as liver cirrhosis, Gaucher disease, glycogen storage disease, Niemann-Pick disease, etc.), considered unsuitable for participation in this study by the investigator;
• Presence of acute infectious disease or chronic infectious disease in the active phase at screening, such as hepatitis B patients who are hepatitis B surface antigen (HbsAg) positive with detectable HBV-DNA indicating viral replication, hepatitis C patients who are anti-HCV antibody positive with detectable HCV-RNA indicating viral replication; positive syphilis screening (positive specific antibody test, negative nonspecific antibody test, and confirmed as non-active infection based on clinical judgment is excluded);
• History of human immunodeficiency virus (HIV) infection, or HIV positive at screening;
• Undergoing major surgery within 1 month prior to screening (high-risk, complex, or difficult procedures, such as thoracoscopic pulmonary bulla resection or thoracoscopic esophageal atresia surgery);
• Received or planned to use recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) within 1 week prior to screening or during the trial;
• Received glucocorticoid (oral or intravenous) or lithium treatment within 1 week prior to screening;
• Received whole blood, white blood cells, or platelet transfusion within 2 weeks prior to screening;
• Received human granulocyte colony-stimulating factor (G-CSF) treatment within 3 months prior to screening;
• Received systemic anti-infective therapy (oral or intravenous) within 72 hours prior to screening;
• History of drug or alcohol abuse, or history of substance abuse;
• Received other clinical trial drugs or treatments within 4 weeks prior to screening;
• History of allergic diseases, being of an allergic constitution, or known allergy to any drug or component of this trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• Beijing Children's Hospital — Beijing

Identifiers

NCT: NCT07724756 · QLC2519-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗