Intrathecal Rituximab in Lymphoid Malignancies Involving Central Nervous System

NCT ID: NCT01596127

Last Updated: 2018-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-24
• Study Completion Date: 2017-03-23

Brief Summary

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.

Detailed Description

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.

Conditions

Leukemia; Lymphoid Malignancies; Metastatic Malignant Neoplasm to the Leptomeninges

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intrathecal Rituximab

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.

Group Type: EXPERIMENTAL

Intrathecal Rituximab

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Rituxan

Eligibility Criteria

Inclusion Criteria

1. Patients must have relapsed or refractory CD20+ lymphoid malignancies with either documented CNS involvement or peripheral nerve infiltration.

2. Patients 3 years of age and older are eligible after 3 patients (age 15 or older) have been treated and did not experience a dose limiting toxicity. Patient 3 to 15 years of age will follow the dose escalation schema independent of the adults.

3. ECOG performance status measure will be used. (ECOG Performance Status less than or equal to 3)

4. Adequate liver function (bilirubin less than or equal to 3 mg/dL within 24 hours of enrollment)

5. Adequate renal function (serum creatinine less than or equal to 3 mg/dL within 24 hours of enrollment)

6. Urine pregnancy test for women of childbearing potential (defined as not post-menopausal for 12 consecutive months or no previous surgical sterilizations). A negative urine pregnancy test is required within 48 hours of initiating study drug.

7. Signed informed consent

Exclusion Criteria

1. Known active meningeal infection

2. History of severe infusion reaction to any monoclonal antibody

• Minimum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elias Jabbour, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

NCI-2012-00849

Identifier Type: REGISTRY

Identifier Source: secondary_id

2011-0844

Identifier Type: -

Identifier Source: org_study_id