Description:
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®).
Title
- Brief Title: Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma
- Official Title: Lenalidomide Plus Rituximab for Recurrent/Refractory CNS and Intraocular Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
112530
- SECONDARY ID:
NCI-2013-00056
- NCT ID:
NCT01542918
Conditions
- Recurrent/Refractory CNS
- Intraocular Lymphoma
Interventions
| Drug | Synonyms | Arms |
|---|
| Lenalidomide | Revlimid | Study intervention |
| Rituximab | Rituxan, MabThera | Study intervention |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Study intervention | Experimental | Lenalidomide Plus Rituximab | |
Eligibility Criteria
Inclusion Criteria:
- 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)
- 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®.
Exclusion Criteria:
- 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
- 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| 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. |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | Objective only applies to patients with recurrent CNS lymphoma not responding to lenalidomide as monotherapy |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | James Rubenstein |
Trial Keywords
- Recurrent
- Refractory
- CNS
- Intraocular
- Lymphoma
Last Updated
August 11, 2020
