Primary Central Nervous System LymphomaPhase 2NCT02113007
Study of High-Dose Rituximab With Temozolomide as Treatment for Primary Central Nervous System (CNS) Lymphoma
A Phase 2 study testing Rituximab plus Temozolomide in people with Primary Central Nervous System Lymphoma, run by SCRI Development Innovations, LLC at 4 sites in United States.
Trial summary
This study will evaluate the safety and efficacy of high-dose rituximab combined with temozolomide in the treatment of patients with Primary Central Nervous System Lymphomas (PCNSL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Central Nervous System Lymphoma
- What is being tested?
- Rituximab plus Temozolomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2014to Feb 2016
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed CD20 positive primary B-cell CNS lymphoma (PCNSL) confirmed by one of the following:
- Brain biopsy or resection;
- Cerebrospinal fluid (CSF) cytology for lymphoma or monoclonal lymphocyte population as defined by cell surface markers.
- No evidence of systemic non-Hodgkin's lymphoma.
- Male or female, and:
- 60 years of age or older, or
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- 18 years of age or older and decline methotrexate-based treatment.
- Measurable contrast-enhancing disease by MRI of brain and or spine (with gadolinium contrast).
- ECOG PS equals 2 or less.
- No more than 2 prior chemotherapy regimens.
- Adequate hematologic, renal, and hepatic function.
- Ability to swallow oral medications.
- Female patients who are not of childbearing potential, and female patients of childbearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum pregnancy test within 72 hours prior to start of treatment.
- Male patients willing to use adequate contraceptive measures.
- Life expectancy 8 weeks or greater.
- HIV negative.
- Archival tumor block (or 20 unstained slides) for biomarker testing. Patients without archived tumor block material will be allowed to participate in the study.
- Willingness and ability to comply with study and followup procedures.
- Ability to understand the nature of this study and give written informed consent.
- Bone marrow biopsy must be negative for lymphoma.
Who cannot join
- Previous treatment with rituximab or other monoclonal antibodies, or temozolomide.
- Prior bone marrow or organ transplantation.
- Chemotherapy or investigational drug therapy for cancer up to 21 days prior to day-1 of study.
- T-cell primary CNS lymphoma.
- Known hypersensitivity to dacarbazine (DTIC).
- Active, clinically serious infection greater than CTCAE grade 2. Patients may be eligible upon resolution of the infection.
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- Positive test results for chronic hepatitis BsAg infection.
- Chronic treatment with steroids or other immunosuppressive agents for medical conditions other than cancer. Patients who require steroids for treatment of tumor-associated cerebral edema are eligible.
- History of other malignancy up to 5 years prior to study entry which could affect compliance with the protocol or interpretation of results. History of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, low grade, early stage, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent, are generally eligible.
- History of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), New York Heart Association Classification III or IV.
- Vaccination with a live-virus vaccine up to 4 weeks prior to onset of study treatment.
- Impairment of gastrointestinal (GI) function or GI disease that, in the opinion of the investigator, may significantly alter the absorption of study drug (e.g., Crohn's disease, ulcerative disease, uncontrolled vomiting, diarrhea, or malabsorption syndrome).
- Significant, concurrent, uncontrolled medical condition which, in the opinion of the investigator, may interfere with patient participation in the study.
- Pregnant or lactating female.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Memorial Cancer Institute
Hollywood, Florida, 33021
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
Yale School of Medicine
New Haven, Connecticut, 06520
Florida Hospital Cancer Institute
Orlando, Florida, 32804
About this study
Official title: Phase II Study of High-Dose Rituximab Combined With Temozolomide as Treatment for Patients With Primary CNS Lymphoma
This study will evaluate the safety and efficacy of high-dose rituximab combined with temozolomide in the treatment of patients with Primary Central Nervous System Lymphomas (PCNSL). This novel combination will be evaluated in PCNSL patients who are 60 years of age or older, or in patients 18 years or older who refuse methotrexate-based treatment.
Read the detailed description
This is a Phase II, multi-centered, single-arm study. A brief patient lead-in portion will be included to assess safety and feasibility. The first six patients enrolled will be monitored weekly for safety during two treatment cycles (4 weeks) for adverse events to assure there are no unexpected or prohibitive toxicities. If safety signals emerge from this group of patients, the protocol may be discontinued or modified.
- Conditions
- Primary Central Nervous System Lymphoma
- Being tested
- Rituximab plus Temozolomide
- Keywords
- Lymphoma; CNS; rituximab; temozolomide
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab plus TemozolomideDrug
Also called Rituximab: Rituxin, MabThera, Temozolomide: Temodar
Treatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab plus Temozolomide | Experimental | Rituximab: 375 mg/m2 IV, days 1, 3, and 5 Temozolomide: 150 mg/m2 PO, days 1-5 Receives: Drug: Rituximab plus Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Patients will be assessed for response by MRI of brain and/or spine after 4 cycles (8 weeks) of treatment according to Response Criteria for Primary CNS Lymphoma. Patients with stable disease or better (CR or PR) will continue treatment for 12 cycles (24 weeks). Complete Response (CR)=no contrast enhancement, normal eye exam. Partial Response (PR)=50 percent decrease in tumor enhancement, minor retinal pigment epithelium abnormality in eye exam. Stable disease (SD)= a change in lesion size that is neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for progressive disease.
Measured: approximately 32 weeks
Secondary outcomes (2)
Progression Free Survival (PFS)
Six and twelve-month CNS progression-free survival rate.
Measured: 6 and 12 months
Number of Participants With Serious and Non-serious Adverse Events as a Measure of Safety.
Patients in the safety lead-in part of the study were monitored for up to 2 treatment cycles (4 weeks) to assure there were no unexpected or prohibitive toxicities. A non-serious adverse event is any untoward medical occurrence. A serious adverse event (SAE) is an event that meets one or more of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; requires intervention to prevent permanent impairment or damage. Specific AE and SAE terms are provided in the Adverse event module.
Measured: up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2014 (estimated)
- Study startJul 2014
- Primary completionFeb 2016
- Study completionFeb 2016
Why it stopped: Closed early due to 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 Primary Central Nervous System LymphomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Kent Shih, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02113007
- Sponsor's protocol ID
- SCRI CNS 20
- Status last verified
- Dec 2016
- First submitted
- 10 Apr 2014
- Last updated
- 7 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of High-Dose Rituximab Combined With Temozolomide as Treatment for Patients With Primary CNS Lymphoma
- ClinicalTrials.gov ID
- NCT02113007
- Acronym / sponsor ID
- SCRI CNS 20
- Conditions
- Primary Central Nervous System Lymphoma
- Keywords
- Lymphoma; CNS; rituximab; temozolomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed early due to slow accrual.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jul 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 14 Apr 2014 (estimated)
- Results
- Posted 7 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and efficacy of high-dose rituximab combined with temozolomide in the treatment of patients with Primary Central Nervous System Lymphomas (PCNSL). This novel combination will be evaluated in PCNSL patients who are 60 years of age or older, or in patients 18 years or older who refuse methotrexate-based treatment.
Detailed description
This is a Phase II, multi-centered, single-arm study. A brief patient lead-in portion will be included to assess safety and feasibility. The first six patients enrolled will be monitored weekly for safety during two treatment cycles (4 weeks) for adverse events to assure there are no unexpected or prohibitive toxicities. If safety signals emerge from this group of patients, the protocol may be discontinued or modified.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab plus Temozolomide | Experimental | Drug: Rituximab plus TemozolomideRituximab: 375 mg/m2 IV, days 1, 3, and 5 Temozolomide: 150 mg/m2 PO, days 1-5 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically confirmed CD20 positive primary B-cell CNS lymphoma (PCNSL) confirmed by one of the following:
- No evidence of systemic non-Hodgkin's lymphoma.
- Male or female, and:
- Measurable contrast-enhancing disease by MRI of brain and or spine (with gadolinium contrast).
- ECOG PS equals 2 or less.
Key exclusion criteria (14 listed)
- Previous treatment with rituximab or other monoclonal antibodies, or temozolomide.
- Prior bone marrow or organ transplantation.
- Chemotherapy or investigational drug therapy for cancer up to 21 days prior to day-1 of study.
- T-cell primary CNS lymphoma.
- Known hypersensitivity to dacarbazine (DTIC).
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 |
|---|---|---|
| Rituximab plus TemozolomideAlso: Rituximab: Rituxin, MabThera, Temozolomide: TemodarTreatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles. | Drug | Rituximab plus Temozolomide |
Primary outcome
Overall Response Rate
Time frame: approximately 32 weeks
Patients will be assessed for response by MRI of brain and/or spine after 4 cycles (8 weeks) of treatment according to Response Criteria for Primary CNS Lymphoma. Patients with stable disease or better (CR or PR) will continue treatment for 12 cycles (24 weeks). Complete Response (CR)=no contrast enhancement, normal eye exam. Partial Response (PR)=50 percent decrease in tumor enhancement, minor retinal pigment epithelium abnormality in eye exam. Stable disease (SD)= a change in lesion size that is neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for progressive disease.
2 secondary outcomes
Progression Free Survival (PFS)
Time frame: 6 and 12 months
Number of Participants With Serious and Non-serious Adverse Events as a Measure of Safety.
Time frame: up to 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kent Shih, M.D. study chair
SCRI Development Innovations, LLC
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab plus Temozolomide in people with Primary Central Nervous System Lymphoma, run by SCRI Development Innovations, LLC at 4 sites 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 20 inclusion and 14 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 7 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 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 7 Feb 2017). 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?
Overall Response Rate (time frame: approximately 32 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 7 Feb 2017.