Population Pharmacokinetic-pharmacodynamic Study of Rituximab in Children With Blood Diseases

To establish a population pharmacokinetic and pharmacodynamic model of rituximab in children with hemopathy. To optimize the administration of rituximab in the treatment of children based on pharmacokinetic model.

Study Overview

• Status: Not yet recruiting
• Conditions: Children; Blood Disease; Rituximab
• Intervention / Treatment: Drug: Rituximab; Drug: Rituximab (once a week)

Detailed Description

hemotherapy for children with lymphoma: rituximab (375mg/m2 BSA) was added intravenously from COPADM1 regimen. once every 3 weeks to 4 weeks, combined with corresponding chemotherapy, a total of 4 times.

Rituximab (375mg/m2 BSA) was administered intravenously for lymphoproliferative diseases and Epstein-Barr(EB) virus-associated B lymphoproliferative diseases after hematopoietic stem cell transplantation. Once a week, a total of 4 times.

Primary immunologic thrombocytopenic purpura(ITP) and autoimmune hemolytic anemia(AIAH) patients received rituximab (100mg/m2 BSA) intravenously once a week, a total of 4 times.

The children were divided into group A and group B according to the disease type, and each group was randomly divided into two groups (group 1 and group 2) and assigned blood collection points.

Burkitt's lymphoma diffuse large B-cell lymphoma follicular lymphoma and other mature B-lymphomas were in group A. Hematopoietic stem cell transplantation, EPstein-Barr virus associated lymphocyte proliferative disease, lymphocyte proliferative change, primary immunologic thrombocytopenic purpura(ITP) and autoimmune hemolytic anemia(AIAH) were in group B.

Group 1: Children in the first group were collected 0, 12, 24, and 72 h after the first dose, 0h before and after the second dose, 0h before and after the third dose, 0h before and after the last dose, 48, and 96 h after the last dose. Venous blood was collected at 12 time points.

Group 2: Children in the second group were collected 0, 12, 48, and 96 h after the first dose, 0h before and after the second dose, 0h before and after the third dose, 0h before and after the last dose, 24, and 72 h after the last dose. Venous blood was collected at 12 time points.

• Study Type: Observational
• Enrollment (Anticipated): 20

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Age 6 months to 18 years, histologically or cytologically proven mature B lymphoma such as Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma, hematopoietic stem cell transplantation, and Epstein-Barr virus associated B lymphoproliferative disease, B cell lymphoproliferative alteration, immune thrombocytopenia. Children with autoimmune hemolytic anemia and other diseases that meet the indication of rituximab and need rituximab monotherapy or combination therapy.

Description

Inclusion Criteria:

• Children aged 6 months to 18 years (including 6 months and 18 years), male or female.
• Burkitt's lymphoma, diffuse large B-cell lymphoma, follicular lymphoma and other mature B-cell lymphoma confirmed by histology or cytology, hematopoietic stem cell transplantation, EB virus associated B-cell proliferative diseases, b-cell proliferative changes, immune thrombocytopenia, Autoimmune hemolytic anemia and other patients with rituximab indications should be treated with rituximab monotherapy or combination.
• Eastern Cooperative Oncology Group(ECOG) physical status score was 0-2.
• Life expectancy was at least six months.
• Women and men with reproductive potential must agree to use effective contraceptive methods during and after treatment.
• The subjects or their parents or guardians fully know and sign the informed consent, and the subjects can cooperate to complete the follow-up.

Exclusion Criteria:

• Patients with known hypersensitivity to rituximab and rat protein.
• Previously known active infection of human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV), except for the following patients: Hepatitis B infection [hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) positive] but negative results of HBV DNA polymerase chain reaction (PCR) can be included in the group.
• A confirmed history of progressive multifocal leukoencephalopathy (PML).
• Exclusion criteria associated with rituximab: tumor cell CD20 negative.
• Received live vaccine within 4 weeks prior to enrollment.
• Received immunoglobulin therapy within 3 months prior to enrollment.
• Participants in the clinical trials of other drugs and taking the test drugs within 3 months.
• Any other medical condition, metabolic abnormality, physical abnormality, or laboratory abnormality of clinical significance that, in the investigator's judgment, has reason to suspect that the patient has a medical condition or condition unsuitable for rituximab or that would affect the interpretation of study results or place the patient at high risk.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
lymphoma patients; Patients with Burkitt's lymphoma, diffuse large B-cell lymphoma, follicular lymphoma and other mature B-lymphoma patients. Patients were randomly divided into two groups for PK blood collection. There were 12 blood sampling sites in each group.	Drug: Rituximab; Chemotherapy for children with lymphoma: rituximab (375mg/m2 BSA) was added intravenously from COPADM1 regimen. once every 3 weeks to 4 weeks, combined with corresponding chemotherapy, a total of 4 times.; Other Names: Rituximab injection
Patients with B lymphoproliferative diseases; Patients with hematopoietic stem cell transplantation and Epstein-Barr virus associated b-cell lymphoproliferative diseases, b-cell lymphoproliferative changes, immune thrombocytopenia, and autoimmune hemolytic anemia. Patients were randomly divided into two groups for pharmacokinetics blood collection. There were 12 blood sampling sites in each group.	Drug: Rituximab (once a week); Rituximab (375mg/m2 BSA) was administered intravenously for lymphoproliferative diseases and EB virus-associated B lymphoproliferative diseases after hematopoietic stem cell transplantation. Once a week, a total of 4 times. ITP and AIHA patients received rituximab (100mg/m2 BSA) intravenously once a week, a total of 4 times.; Other Names: Rituximab injection (once a week)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
concentration of rituximab in plasma	the data of plasma drug concentration and time.	400 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Adverse events were recorded to evaluate the safety of the studied drugs.	400 days

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 10, 2022
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: February 28, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: YQ-KY-202101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No