Neoplasms

Blood and Lymph Conditions

All Conditions

Nervous System Diseases

Leukemia

Central Nervous System Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Phase I Starting Dose: Rituximab administered via lumbar puncture at dose of 10 - 25 mg twice weekly according to the dose escalation.

Phase II Rituximab Starting Dose: Maximum tolerated dose from Phase I.

Phase I: Starting dose Rituximab 10 mg intrathecally twice weekly until 2 consecutive CSF samples are negative for the presence of blast cells. Thereafter, rituximab 10 mg intrathecally weekly for additional 4 weeks, followed by intrathecal rituximab 10 mg administered once every other week for an additional 8 weeks.

Phase II Starting Dose of Rituximab: Maximum tolerated dose from Phase I.

Intrathecal Rituximab

Elias Jabbour, MD

The goal of this clinical research study is to learn about the safety and effectiveness of rituximab given by spinal tap in patients with lymphoid malignancies involving the central nervous system.

A spinal tap (also called a lumbar puncture) is when fluid surrounding the spinal cord is collected by inserting a needle into the lower back. The affected area is numbed with local anesthetic during the procedure. It will also be used to give chemotherapy in this study.

Rituximab is designed to bind to a protein, called CD20, that is on the surface of the leukemia cells. This may cause the leukemia cells to die.

Study Groups and Study Drug Administration:

If you are found to be eligible, you will be assigned to a study group based on when you join this study. Up to 12 participants will be enrolled in the Phase I portion of the study, and up to 13 participants will be enrolled in Phase II.

If you are enrolled in the Phase I portion, the dose of rituximab you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of rituximab. Each new group will receive a higher dose of rituximab than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of rituximab is found.

If you are enrolled in the Phase II portion, you will receive rituximab at the highest dose that was tolerated in the Phase I portion.

Study Visits:

Once enrolled, you will return to the clinic and receive the study drug by spinal tap up to 2 times a week. You will receive treatment twice a week until 2 CSF samples in a row do not show any leukemia cells. After that, you will receive treatment 1 time a week for an additional 4 weeks, and then you will receive treatment once every other week for an additional 8 weeks. The number of doses you receive will depend on how many doses the study doctor thinks is needed.

At each study visit the following procedures will be performed:

* You will have a physical exam, including measurement of your weight, and vital signs. °Your vital signs will be measured every 15 minutes for 1 hour after each dose of rituximab.
* You will be asked how well you are able to perform the normal activities of daily living (performance status).
* You will be asked about any drugs you may be taking and any side effects you may experiencing.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* A sample of cerebral spinal fluid may be collected from the lumbar puncture to verify the absence or presence of blast cells.

Follow-Up:

About 30 days after your last dose of study drug you will be contacted by the study staff by telephone and asked about any drugs you may be taking and any side effects you may experiencing. This call should take about 10 minutes.

Long-term Follow-up:

Every 6 to 12 months you may be contacted by the study staff by telephone and asked about any drugs you may be taking and any side effects you may experiencing. This call should take about 10 minutes.

You may be given other drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

Length of Treatment:

The number of treatments you receive will depend on how long it takes for there to be no leukemia cells in the CSF samples. Once this happens, you will have treatments for an additional 12 weeks. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

This is an investigational study. Rituximab is FDA approved and commercially available for the treatment of relapsed and/or refractory lymphoid malignancies involving the central nervous system. Receiving rituximab by spinal tap is considered investigational.

Up to 25 patients will take part in this study. All will be enrolled at MD Anderson.

Intrathecal Rituximab in Lymphoid Malignancies Involving Central Nervous System

Safety and Efficacy of Intrathecal Rituximab in Patients With Lymphoid Malignancies Involving the Central Nervous System

The percentage of participants whose cancer shrinks or disappears after treatment where participants are considered as responding to therapy if the Cerebrospinal fluid (CSF) is without evidence of blast cells after four lumbar punctures with rituximab.

MTD is dose level at which at least 1 of 3 participants experiences a dose-limiting toxicity (DLT). DLTdefined as clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and meeting the NCI common terminology criteria that are CTCAE Grade 3 or 4.

M.D. Anderson Cancer Center

Phase I Starting Dose: Rituximab administered via lumbar puncture at dose of 10 - 25 mg twice weekly according to the dose escalation.

Phase II Rituximab Starting Dose: Maximum tolerated dose from Phase I.

Intrathecal Rituximab: Phase I: Starting dose Rituximab 10 mg intrathecally twice weekly until 2 consecutive CSF samples are negative for the presence of blast cells. Thereafter, rituximab 10 mg intrathecally weekly for additional 4 weeks, followed by intrathecal rituximab 10 mg administered once every other week for an additional 8 weeks.

Phase II Starting Dose of Rituximab: Maximum tolerated dose from Phase I.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Elias Jabbour MD/Associate Professor

Response Rate

Multiple dose levels were designed with a starting dose of 10 mg per injection followed by 25 mg once safety was established in the first 3 patients treated at the first dose level. The study moved tot he next dose level. Due to lack of response and slow accrual, participants were never treated on the next dose level and the study was terminated

Maximum Tolerated Dose (MTD) of Rituximab

Overall Study

Immune System Diseases

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Anti-Infective Agents

Dermatologic Agents

Reproductive Control Agents

Hematinics

Cytarabine

Methotrexate

Liver Extracts

From May 2015 to December 2020, 16 children with NHL who were diagnosed in the Department of Pediatric Oncology of Sun Yat-sen Memorial Hospital of Sun Yat-sen University agreed to receive RTX intrathecal therapy and signed an informed consent form. Among them, there were 13 males and 3 females, with a male-to-female ratio of 4.33:1.00, an age of 5.1-13.1 years, and an average age of onset of 8.5 years.

1.2 Diagnosis All children are diagnosed according to WHO lymphoma typing criteria by pathomorphological classification and immunotyping of tissue or bone marrow .

Exclusion Criteria Patients with severe organic diseases such as heart, liver and kidney, allergic to rituximab.

All children were treated with a modified NHL-BFM95 regimen for children NHL with the addition of rituximab, both intravenous and intrathecal, and rituximab intrathecal infusion is scheduled to be used simultaneously with rituximab intravenous drip. rituximab intrathecal doses are 10 mg, 15 mg, and 20 mg in increments every 3 weeks. rituximab intrathecal injection does not use methotrexate or/and cytarabine intrathecaline chemotherapy.

intrathecal rituximab

Yang Li

Objective: This study demonstrated that the efficacy and safety of intrathecal(IT) rituximab in the treatment of stage Ⅲ and Ⅳ non-Hodgkin lymphoma(NHL) in children.

Methods: We reported 16 children were histologically diagnosed as stage Ⅲ and Ⅳ NHL from September 2015 to December 2020 who received IT rituximab in Pediatric Oncology of Sun Yat-Sen Memorial Hospital were restrospectively analyzed. The clinical manifestations, central nervous system involvement,treatment plan and prognosis of patients were analyzed....

ALL patients were pathologically positive for CD20 received the modified NHL-BFM 95, while IT rituximab was arranged the day before the chemotherapy, which was simultaneously used with the intravenous infusion of rituximab. The median time of doses received by each patient was 5 times, every three weeks, with the IT dose of 10 mg,15 mg, and 20 mg in increments.

Malignant lymphoma is one of the most common malignancies in children, with approximately 60 percent of cases being B-cell, non-hodgkin lymphoma (NHL) . NHL in children progresses rapidly, prone to bone marrow and central nervous system (CNS) involvement , CNS-infested NHL has a poor prognosis regardless of primary or secondary , high-intensity chemotherapy, intravenous rituximab (RTX), radiotherapy, and hematopoietic stem cell transplantation, HSCT) has limited efficacy in the treatment of these children because only a small percentage of drugs/antibodies can penetrate the blood-brain barrier . Only a limited number of intrathecal agents, primarily methotrexate, steroids, and cytarabine, have been identified that have demonstrated safety in the use of CNS-violated NHL but have not improved long-term survival in these children . Therefore, whether safe and effective intrathecal drugs can be found is the focus of the treatment and prevention of CNS-infused NHL.

Most B-cell NHL tumors express CD20 antigen in tumor tissues , RTX is a chimeric monoclonal antibody specific to B-cell CD20 antigen, and a large number of studies have confirmed that intravenous infusion of RTX has a good effect on adult and pediatric B-cell NHL . However, intravenous RTX concentrations in cerebrospinal fluid are low, ranging from 0.1 to 4.4 percent of the blood concentration, and repeated intravenous use does not increase its drug concentration in the cerebrospinal fluid . Recent small clinical studies have shown that intrathecal RTX injection is safe in adult lymphoma patients , but there are no domestic cases of intrathecal RTX use in childhood lymphoma. In this paper, 16 clinical cases of intrathecal RTX injection of stage III and IV. B-cell NHL were analyzed to explore the safety and efficacy of RTX intrathecal therapy.

Safety and Efficacy of Intrathecal Rituximab in 16 Children of Stage Ⅲ、ⅣNon-Hodgkin Lymphoma

This data can be requested by sending an email to the author.

DFS is the time from grouping to evidence of disease recurrence

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Symptoms and General Pathology

Meningeal Carcinomatosis

Lymphoma, B-Cell

Meningitis

Neuroinflammatory Diseases

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

B-cell Lymphoma

Annarita Conconi, MD

Andres JM Ferreri, MD

The purpose of this study is to define the safety profile of rituximab given intrathecally in lymphomatous meningitis related to CD20+ non-Hodgkin's lymphomas.

A Phase I Study of Intrathecal Rituximab in Patients With Lymphomatous Meningitis

International Extranodal Lymphoma Study Group (IELSG)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intrathecal Rituximab in Lymphoid Malignancies Involving Central Nervous System	NCT01596127	Leukemia Lymphoid Malign... Metastatic Mali...	Intrathecal Rit...	3 Years -	M.D. Anderson Cancer Center
Safety and Efficacy of Intrathecal Rituximab in 16 Children of Stage Ⅲ、ⅣNon-Hodgkin Lymphoma	NCT06190457	Lymphoma, Non-H... Child, Only	intrathecal rit...	1 Day - 14 Years	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
A Phase I Study of Intrathecal Rituximab in Patients With Lymphomatous Meningitis	NCT00210340	Lymphoma, B Cel...	intrathecal rit...	18 Years -	International Extranodal Lymphoma Study Group (IELSG)
A Phase I Study of Intrathecal Rituximab in Patients With Lymphomatous Meningitis	NCT00210340	Lymphoma, B Cel...	intrathecal rit...	18 Years -	International Extranodal Lymphoma Study Group (IELSG)

Spots Global Cancer Trial Database for intrathecal rituximab