Recurrent/Refractory CNSPhase 1NCT01542918
Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma
A Phase 1 study testing Lenalidomide and Rituximab in people with Recurrent/Refractory CNS and Intraocular Lymphoma, run by James Rubenstein at 1 site in United States.
Trial summary
This is a Phase I study, which means that the goal is to see if the study treatment is safe. The purpose of this study is to test the safety of Lenalidomide at different dose levels, and to test the safety of Lenalidomide alone or in combination with Rituximab (also known as Rituxan®). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent/Refractory CNS, Intraocular Lymphoma
- What is being tested?
- Lenalidomide and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Dec 2012to 30 Aug 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to give written informed consent and willingness to comply with the requirements of the protocol
- Age eighteen years or older
- Tumors must be CD20+ on prior pathologic analysis
- All prospective participants must have an Ommaya reservoir (or equivalent ventricular access device) inserted as part of their standard clinical care prior to initiation of study treatment.
- No concurrent methotrexate, thiotepa, cytarabine, or investigational agents
- Absolute neutrophil count (ANC) > 1,500 (growth factors permitted)
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- Platelets >50,000 (platelet transfusion allowed)
- Total bilirubin </= 1.5 x upper limit of normal (ULN)
- aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) </= 3 x ULN.
- Stable dose of glucocorticoids pre-therapy. If patients are receiving dexamethasone, the dose of dexamethasone should not increase during the 96 hours prior to initiation of therapy.
- Renal function assessed by calculated creatinine clearance. Patients must have calculated creatinine clearance (CrCl) >/= 60ml/min by Cockcroft-Gault formula or 24 hour urine demonstrating CrCl >/= 60ml/min .
- Females of childbearing potential (FCBPs)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 Milli-International Units per millilitre (mIU/mL) within 10 - 14 days and again within 24 hours prior to receiving lenalidomide for Cycle 1 and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBPs must also agree to ongoing pregnancy testing and for 28 days after receiving their last dose of lenalidomide.
- Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin may use warfarin or low molecular weight heparin).
- All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
Who cannot join
- Intraventricular chemotherapy or radiation therapy within 4 days of starting treatment
- Intravenous rituximab within 30 days of starting treatment
- Persistent neurotoxicity from intraventricular methotrexate, cytarabine, thiotepa
- Anticipated survival of less than 1 month
- Pregnant women and women of child-bearing potential who are not using an effective method of birth control.
- Known hypersensitivity to thalidomide or lenalidomide
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- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
- Contraindication to aspirin. If unable to take aspirin, contraindication to warfarin or low molecular weight heparin.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
This is a Phase I study, which means that the goal is to see if the study treatment is safe. The purpose of this study is to test the safety of Lenalidomide at different dose levels, and to test the safety of Lenalidomide alone or in combination with Rituximab (also known as Rituxan®).
Read the detailed description
Rationale for the Proposed Study
There is evidence that immunomodulatory drugs such as lenalidomide stimulate immune effectors such as natural killer (NK) cells, and thus promote rituximab efficacy via ADCC. Because of the evidence for synergy between rituximab and lenalidomide in NHL, patients who do not respond to lenalidomide monotherapy will receive combined intravenous plus intraventricular rituximab in addition to lenalidomide. To maximize delivery to the central nervous system (CNS), the investigators propose to administer rituximab via both intravenous and intraventricular routes. The rationale for intraventricular administration of rituximab is the demonstration that approximately 0.1% of systemically administered rituximab penetrates the cerebral spinal fluid (CSF) but that intraventricular administration of rituximab is both feasible and achieves high concentrations that are associated with anti-lymphoma activity. This study will thus build upon the two Phase 1 trials of intraventricular rituximab that have been conducted at University of California, San Francisco (UCSF) to define the safety of the intraventricular route of administration; this study will, however, be the first to evaluate the combination of intraventricular plus intravenous treatment.
The rationale for intravenous administration of rituximab in recurrent CNS lymphoma is that the blood-brain-barrier is likely partially disrupted, particularly when there is lymphoma-associated contrast enhancement detectable on the MRI, and the fact that there is evidence for activity when rituximab is administered intravenously, both as monotherapy (Batchelor et al., 2011) and potentially in combination with chemotherapy.
- Conditions
- Recurrent/Refractory CNS, Intraocular Lymphoma
- Being tested
- Lenalidomide, Rituximab
- Keywords
- Recurrent, Refractory, CNS, Intraocular, Lymphoma
- Medical subject headings
- Recurrence, Intraocular Lymphoma, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called Revlimid
Formulation of Dosage forms: 5 mg, 10 mg, 15 mg and 25 mg capsules.
Dosage: 10 mg - 30 mg (Treatment 1 and Treatment 2)
Route of administration: Oral
RituximabDrug
Also called Rituxan, MabThera
Formulation of Dosage forms: 100 mg/IO mL and 500 mg/50 mL solution in a single-use vial
Dosage: 375 mg/m2, intravenous (Treatment 2, Cycle 1 only); 25 mg intraventricular injection (Treatment 2, all cycles)
Route of administration: Intravenous (Treatment 2, Cycle 1 only); Intraventricular injection (Treatment 2, all cycles)
| Study group | Role | What they receive |
|---|---|---|
| Study intervention | Experimental | Lenalidomide Plus Rituximab Receives: Drug: Lenalidomide; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish the maximal tolerated dose (MTD) of Lenalidomide in patients with recurrent CNS NHL and intraocular NHL
Measured: Participants will be followed for the duration of treatment, an expected average of 4 months.
Secondary outcomes (5)
To define the extent of cerebrospinal fluid (CSF) penetration of lenalidomide.
Measured: Participants will have CSF withdrawn every 4 weeks while on treatment. Average study participation is approximately 4 months.
To assess the clinical efficacy Lenalidomide monotherapy as measured by cytologic, neurologic, radiographic, and ocular (for patients with intraocular lymphoma) response criteria.
Measured: Participants will have weekly evaluations at clinic visits for the duration of treatment. Average study participation is approximately 4 months.
To define the immunological effects of lenalidomide using flow-cytometry CSF as well as genomic markers of recurrent/refractory CNS lymphoma.
Measured: Participants will have CSF withdrawn every 4 weeks while on treatment. Average study participation is approximately 4 months.
To assess the clinical efficacy of combined intraventricular plus systemic rituximab administration in combination with lenalidomide as measured by cytologic, neurologic, and radiographic response criteria.
Objective only applies to patients with recurrent CNS lymphoma not responding to lenalidomide as monotherapy
Measured: Participants will have weekly evaluations at clinic visits for the duration of treatment. Average study participation is approximately 4 months.
To determine a potential impact of intravenous rituximab administration on the rate of rituximab clearance from the CSF after intraventricular rituximab administration.
Measured: Participants will have CSF withdrawn every 4 weeks while on treatment. Average study participation is approximately 4 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2012 (estimated)
- Study start17 Dec 2012
- Primary completion7 Apr 2016
- Study completion30 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent/Refractory CNSStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- James Rubenstein
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene, Genentech, Inc.
- Responsible party
- Sponsor-investigator, James Rubenstein, University of California, San Francisco
- Investigators
- James Rubenstein, MD, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01542918
- Sponsor's protocol ID
- 112530
- Other IDs
- NCI-2013-00056
- Status last verified
- Aug 2020
- First submitted
- 27 Feb 2012
- Last updated
- 11 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rubenstein JL, Geng H, Fraser EJ, Formaker P, Chen L, Sharma J, Killea P, Choi K, Ventura J, Kurhanewicz J, Lowell C, Hwang J, Treseler P, Sneed PK, Li J, Wang X, Chen N, Gangoiti J, Munster PN, Damato B. Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma. Blood Adv. 2018 Jul 10;2(13):1595-1607. doi: 10.1182/bloodadvances.2017014845.
PubMed 29986852
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma
- ClinicalTrials.gov ID
- NCT01542918
- Acronym / sponsor ID
- 112530
- Conditions
- Recurrent/Refractory CNS, Intraocular Lymphoma
- Keywords
- Recurrent, Refractory, CNS, Intraocular, Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- James RubensteinUniversity, hospital or other
- Collaborators
- Celgene, Genentech, Inc.
- Study start
- 17 Dec 2012 (actual)
- Primary completion
- 7 Apr 2016 (actual)
- Study completion
- 30 Aug 2016 (actual)
- First posted
- 2 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I study, which means that the goal is to see if the study treatment is safe. The purpose of this study is to test the safety of Lenalidomide at different dose levels, and to test the safety of Lenalidomide alone or in combination with Rituximab (also known as Rituxan®).
Detailed description
Rationale for the Proposed Study
There is evidence that immunomodulatory drugs such as lenalidomide stimulate immune effectors such as natural killer (NK) cells, and thus promote rituximab efficacy via ADCC. Because of the evidence for synergy between rituximab and lenalidomide in NHL, patients who do not respond to lenalidomide monotherapy will receive combined intravenous plus intraventricular rituximab in addition to lenalidomide. To maximize delivery to the central nervous system (CNS), the investigators propose to administer rituximab via both intravenous and intraventricular routes. The rationale for intraventricular administration of rituximab is the demonstration that approximately 0.1% of systemically administered rituximab penetrates the cerebral spinal fluid (CSF) but that intraventricular administration of rituximab is both feasible and achieves high concentrations that are associated with anti-lymphoma activity. This study will thus build upon the two Phase 1 trials of intraventricular rituximab that have been conducted at University of California, San Francisco (UCSF) to define the safety of the intraventricular route of administration; this study will, however, be the first to evaluate the combination of intraventricular plus intravenous treatment.
The rationale for intravenous administration of rituximab in recurrent CNS lymphoma is that the blood-brain-barrier is likely partially disrupted, particularly when there is lymphoma-associated contrast enhancement detectable on the MRI, and the fact that there is evidence for activity when rituximab is administered intravenously, both as monotherapy (Batchelor et al., 2011) and potentially in combination with chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study intervention | Experimental | Drug: Lenalidomide, Drug: RituximabLenalidomide Plus Rituximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Ability to give written informed consent and willingness to comply with the requirements of the protocol
- Age eighteen years or older
- Tumors must be CD20+ on prior pathologic analysis
- All prospective participants must have an Ommaya reservoir (or equivalent ventricular access device) inserted as part of their standard clinical care prior to initiation of study treatment.
- No concurrent methotrexate, thiotepa, cytarabine, or investigational agents
Key exclusion criteria (9 listed)
- Intraventricular chemotherapy or radiation therapy within 4 days of starting treatment
- Intravenous rituximab within 30 days of starting treatment
- Persistent neurotoxicity from intraventricular methotrexate, cytarabine, thiotepa
- Anticipated survival of less than 1 month
- Pregnant women and women of child-bearing potential who are not using an effective method of birth control.
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 |
|---|---|---|
| LenalidomideAlso: RevlimidFormulation of Dosage forms: 5 mg, 10 mg, 15 mg and 25 mg capsules. Dosage: 10 mg - 30 mg (Treatment 1 and Treatment 2) Route of administration: Oral | Drug | Study intervention |
| RituximabAlso: Rituxan, MabTheraFormulation of Dosage forms: 100 mg/IO mL and 500 mg/50 mL solution in a single-use vial Dosage: 375 mg/m2, intravenous (Treatment 2, Cycle 1 only); 25 mg intraventricular injection (Treatment 2, all cycles) Route of administration: Intravenous (Treatment 2, Cycle 1 only); Intraventricular injection (Treatment 2, all cycles) | Drug | Study intervention |
Primary outcome
To establish the maximal tolerated dose (MTD) of Lenalidomide in patients with recurrent CNS NHL and intraocular NHL
Time frame: Participants will be followed for the duration of treatment, an expected average of 4 months.
5 secondary outcomes
To define the extent of cerebrospinal fluid (CSF) penetration of lenalidomide.
Time frame: Participants will have CSF withdrawn every 4 weeks while on treatment. Average study participation is approximately 4 months.
To assess the clinical efficacy Lenalidomide monotherapy as measured by cytologic, neurologic, radiographic, and ocular (for patients with intraocular lymphoma) response criteria.
Time frame: Participants will have weekly evaluations at clinic visits for the duration of treatment. Average study participation is approximately 4 months.
To define the immunological effects of lenalidomide using flow-cytometry CSF as well as genomic markers of recurrent/refractory CNS lymphoma.
Time frame: Participants will have CSF withdrawn every 4 weeks while on treatment. Average study participation is approximately 4 months.
To assess the clinical efficacy of combined intraventricular plus systemic rituximab administration in combination with lenalidomide as measured by cytologic, neurologic, and radiographic response criteria.
Time frame: Participants will have weekly evaluations at clinic visits for the duration of treatment. Average study participation is approximately 4 months.
To determine a potential impact of intravenous rituximab administration on the rate of rituximab clearance from the CSF after intraventricular rituximab administration.
Time frame: Participants will have CSF withdrawn every 4 weeks while on treatment. Average study participation is approximately 4 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- Derived from this study: PubMed 29986852Rubenstein JL, Geng H, Fraser EJ, Formaker P, Chen L, Sharma J, Killea P, Choi K, Ventura J, Kurhanewicz J, Lowell C, Hwang J, Treseler P, Sneed PK, Li J, Wang X, Chen N, Gangoiti J, Munster PN, Damato B. Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma. Blood Adv. 2018 Jul 10;2(13):1595-1607. doi: 10.1182/bloodadvances.2017014845.
- Individual participant dataSharing planned: No
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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.
James Rubenstein, MD, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenalidomide and Rituximab in people with Recurrent/Refractory CNS and Intraocular Lymphoma, run by James Rubenstein 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 15 inclusion and 9 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: finished, as of the sponsor's last update on 11 Aug 2020. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To establish the maximal tolerated dose (MTD) of Lenalidomide in patients with recurrent CNS NHL and intraocular NHL (time frame: Participants will be followed for the duration of treatment, an expected average of 4 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01542918, which also lists 1 linked publication.
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 11 Aug 2020.