LeukemiaPhase 1/2NCT01596127
Intrathecal Rituximab in Lymphoid Malignancies Involving Central Nervous System
A Phase 1/2 study testing Intrathecal Rituximab in people with Leukemia and Lymphoid Malignancies, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Leukemia, Lymphoid Malignancies, Metastatic Malignant Neoplasm to the Leptomeninges
- What is being tested?
- Intrathecal Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2013to 23 Mar 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have relapsed or refractory CD20+ lymphoid malignancies with either documented CNS involvement or peripheral nerve infiltration.
- 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.
- ECOG performance status measure will be used. (ECOG Performance Status less than or equal to 3)
- Adequate liver function (bilirubin less than or equal to 3 mg/dL within 24 hours of enrollment)
- Adequate renal function (serum creatinine less than or equal to 3 mg/dL within 24 hours of enrollment)
- 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.
- Signed informed consent
Who cannot join
- Known active meningeal infection
- History of severe infusion reaction to any monoclonal antibody
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Safety and Efficacy of Intrathecal Rituximab in Patients With Lymphoid Malignancies Involving the Central Nervous System
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.
Read the 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.
- Being tested
- Intrathecal Rituximab
- Keywords
- relapsed CD20+ lymphoid malignancies, refractory CD20+ lymphoid malignancies, Rituximab, Intrathecal Rituximab, CNS, Leptomeningeal disease, LMD, central nervous system disease, Relapsed lymphoid malignancies, refractory lymphoid malignancies, CNS leukemia, intrathecal chemotherapy, cerebrospinal fluid, CSF, lumbar puncture, LP
- Medical subject headings
- Leukemia, Meningeal Carcinomatosis, Meningeal Neoplasms, Central Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrathecal RituximabDrug
Also called Rituxan
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.
| Study group | Role | What they receive |
|---|---|---|
| Intrathecal Rituximab | Experimental | 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. Receives: Drug: Intrathecal Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
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.
Measured: 2 weeks
Secondary outcomes (1)
Maximum Tolerated Dose (MTD) of 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.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2012 (estimated)
- Study start24 Jan 2013
- Primary completion23 Mar 2017
- Study completion23 Mar 2017
Why it stopped: Slow Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elias Jabbour, MD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01596127
- Sponsor's protocol ID
- 2011-0844
- Other IDs
- NCI-2012-00849
- Status last verified
- Apr 2018
- First submitted
- 8 May 2012
- Last updated
- 24 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Intrathecal Rituximab in Patients With Lymphoid Malignancies Involving the Central Nervous System
- ClinicalTrials.gov ID
- NCT01596127
- Acronym / sponsor ID
- 2011-0844
- Keywords
- relapsed CD20+ lymphoid malignancies, refractory CD20+ lymphoid malignancies, Rituximab, Intrathecal Rituximab, CNS, Leptomeningeal disease, LMD, central nervous system disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow Accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 24 Jan 2013 (actual)
- Primary completion
- 23 Mar 2017 (actual)
- Study completion
- 23 Mar 2017 (actual)
- First posted
- 10 May 2012 (estimated)
- Results
- Posted 27 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intrathecal Rituximab | Experimental | Drug: Intrathecal RituximabPhase 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. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have relapsed or refractory CD20+ lymphoid malignancies with either documented CNS involvement or peripheral nerve infiltration.
- 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.
- ECOG performance status measure will be used. (ECOG Performance Status less than or equal to 3)
- Adequate liver function (bilirubin less than or equal to 3 mg/dL within 24 hours of enrollment)
- Adequate renal function (serum creatinine less than or equal to 3 mg/dL within 24 hours of enrollment)
Key exclusion criteria (2 listed)
- Known active meningeal infection
- History of severe infusion reaction to any monoclonal antibody
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrathecal RituximabAlso: RituxanPhase 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. | Drug | Intrathecal Rituximab |
Primary outcome
Response Rate
Time frame: 2 weeks
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.
1 secondary outcome
Maximum Tolerated Dose (MTD) of Rituximab
Time frame: 2 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elias Jabbour, MD study chair
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Intrathecal Rituximab in people with Leukemia and Lymphoid Malignancies, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2018.