Primary Central Nervous System LymphomaPhase 1/2REMLANCT04120350
R2-MTX With Lenalidomide Maintenance in Newly-diagnosed PCNSL:a Multicenter Phase Ib/II Stuty
A Phase 1/2 study testing Methotrexate, Rituximab and Lenalidomide in people with Primary Central Nervous System Lymphoma, run by Peking Union Medical College Hospital at 1 site in China.
Trial summary
This is a multicenter prospective single arm phase Ib/II study, and the purpose of this study is to evaluate the safety and efficiency of R2-MTX regimen (rituximab \& lenalidomide \& methotrexate) combined with lenalidomide maintenance in newly-diagnosed primary central nervous system lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Central Nervous System Lymphoma
- What is being tested?
- Methotrexate, Rituximab and Lenalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteChina
- Study dates
- 16 Aug 2019to Aug 2024
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly-diagnosed primary vitreoretinal lymphoma
- ECOG≤2
- creatinine clearance rate (CCR) ≥ 50ml/h, according to Cockcroft-Gault
- Total bilirubin < 2 upper limits of normal, alanine aminotransferase(ALT) < 3 upper limits of normal
- HIV-Ab negative
- Sign the Informed consent
- Women of childbearing potential must understand that the study medication could have a potential teratogenic risk. They should undergo complete contraception during the study period.
- Male subjects must agree to use condoms throughout study drug therapy.
Who cannot join
- Pre-existing uncontrolled active infection
- Clinical evidence of grade 3 or 4 heart failure as defined by the New York Heart Association criteria
- systemic lymphoma involved CNS
- Pregnancy or active lactation
- Co-existing tumors
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Daobin Zhou
Beijing, Dongcheng District, 100730
Yan Zhang, MD, +86 13810000485, zhangyan10659@pumch.cn
About this study
Official title: R2-MTX Regimen Combined With Lenalidomide Maintenance as Frontline Therapy for Primary Central Nervous System Lymphoma: a Multicenter Prospective Single Arm Trial.
This is a multicenter prospective single arm phase Ib/II study, and the purpose of this study is to evaluate the safety and efficiency of R2-MTX regimen (rituximab \& lenalidomide \& methotrexate) combined with lenalidomide maintenance in newly-diagnosed primary central nervous system lymphoma. 2-year Progression free survival (PFS) of the cohort is the primary endpoint.
Read the detailed description
There are 2 section of this trial. Step1 is a phase Ib study.The patients will be treated with R2-MTX regimen (Rituximab 375mg/m2 IV d0, methotrexate 3.5g/m2 civ d1, lenalidomide 15-25mg d1-14, 21 days per cycle) as induction regimen.The dose of rituximab and methotrexate is fixed dose. This is a 3+3 design Ib phase dose-escalation study to determined the maximum tolerated dose(MTD) of lenalidomide dose in combined regimen. 3 levels of lenalidomide dose will be investigated, 15mg, 20mg and 25mg. If the DLT is not found, the dose of 25mg qd will be used for phase II trial.
[update 02-Jun-2020:the recommended phase II doses is 25mg d1-14]
Step 2 is a single-arm phase 2 study with fixed does of R2-MTX regimen in newly-diagnosed PCNSL patients. The response will be evaluated every 2 cycles. Patients who achieved complete remission (CR) or partial remission (PR) will receive further treatment, and there are 6 cycles of R2-MTX regimen for the induction. The patients with stable disease (SD) or progressed disease (PD) will withdraw from the trial and receive salvage regimens. After total 6 induction cycles, the investigators evaluate the efficiency again, the patients with CR or PR will go to lenalidomide maintenance for 2 years or until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion. And the patients with SD or PD will receive salvage regimen.
[update 02-Jun-2020:Younger patients(≤60 years) who achieve PR after 6 cycles of induction therapy will be candidates of high-dose chemotherapy and stem cell rescue. Lenalidomide maintenance will be administed after the high-dose chemotherapy. Older patients(>60 years) who achieve PR after 6 cycles of induction will go to lenalidomide maintenance directly.] During following-up, surveillance examination and brain magnetic resonance imaging (MRI) scans can be performed every 3 months up to the first 2 years, followed by doctor visit every 6 months up to 5 years or the disease relapses.
- Conditions
- Primary Central Nervous System Lymphoma
- Being tested
- Methotrexate, Rituximab, Lenalidomide
- Keywords
- lenalidomide, rituximab, methorexate, Primary Central Nervous System Lymphoma, maintenance therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol
RituximabDrug
375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol
LenalidomideDrug
In phase 1b study, a 3+3 design dose- escalation will be taken. 3 levels should be tested, 15/20/25mg orally d1-14, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol.
[update 02-Jun-2020: the phase Ib trial has finished,and no MDT was obsevered in 25mg group. So the recommanded phase II dose was 25mg.] In phase II study, 25mg daily is considered as an experiment dose for the induction cycles.
In both phase Ib and II study, the does of lenalidomide maintenance is fixed to 25mg orally d1-21 every 28 days for 1 cycle. The duration of maintenance is 2 years.
| Study group | Role | What they receive |
|---|---|---|
| R2-MTX-LEN | Experimental | Phase Ib:Experimental arm will be treated with R2-MTX regimen for 6 cycles as initiate induction, the dose of lenalidomide was escalated from 15mg, 20mg, 25mg to test DLT by 3+3 design, meanwhile the dose of rituximab and methotrexate is fixed. If the patients achieved CR or PR by MRI and CSF evaluation, they processed to lenalidomide maintenance for 2 years.
Phase II: the patients will be treated by fixed dose of R2-MTX regimen (established lenalidomide dose from phase Ib study) for 6 cycles. the efficiency evaluation will be performed every 2 cycles, the patients who achieved CR or PR will finish the total 6 cycles of induction therapy, then begin the stage of lenalidomide maintenance for 2 years. Follow-ups should be taken for 5 years. Receives: Drug: Methotrexate; Drug: Rituximab; Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
2 years progression-free survival
2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow-up without relapsing
Measured: From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Secondary outcomes (2)
2 years overall survival
2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow-up alive
Measured: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
dose-limiting toxicity(DLT)
all treatment-related, critically relevant grade 3/4 adverse event (AE) that occured in the first 21 days after the start of the first treatment.
Measured: from the start of the first dose of lenalidomide to the finish of first cycle of induction(21 days for each cycle).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2019
- Study start16 Aug 2019
- Primary completionAug 2022 (estimated)
- Study completionAug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Central Nervous System LymphomaStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe 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
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Tiantan Hospital, Xuanwu Hospital, Beijing, Peking University Third Hospital, Beijing Hospital, Peking University First Hospital, Chinese PLA General Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04120350
- Sponsor's protocol ID
- PUMCH-NHL-004
- Acronym
- REMLA
- Status last verified
- Jun 2020
- First submitted
- 28 Sep 2019
- Last updated
- 5 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- R2-MTX Regimen Combined With Lenalidomide Maintenance as Frontline Therapy for Primary Central Nervous System Lymphoma: a Multicenter Prospective Single Arm Trial.
- ClinicalTrials.gov ID
- NCT04120350
- Acronym / sponsor ID
- REMLA / PUMCH-NHL-004
- Conditions
- Primary Central Nervous System Lymphoma
- Keywords
- lenalidomide, rituximab, methorexate, Primary Central Nervous System Lymphoma, maintenance therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Collaborators
- Beijing Tiantan Hospital, Xuanwu Hospital, Beijing, Peking University Third Hospital, Beijing Hospital, Peking University First Hospital, Chinese PLA General Hospital
- Study start
- 16 Aug 2019 (actual)
- Primary completion
- Aug 2022 (estimated)
- Study completion
- Aug 2024 (estimated)
- First posted
- 9 Oct 2019 (actual)
- 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 multicenter prospective single arm phase Ib/II study, and the purpose of this study is to evaluate the safety and efficiency of R2-MTX regimen (rituximab \& lenalidomide \& methotrexate) combined with lenalidomide maintenance in newly-diagnosed primary central nervous system lymphoma. 2-year Progression free survival (PFS) of the cohort is the primary endpoint.
Detailed description
There are 2 section of this trial. Step1 is a phase Ib study.The patients will be treated with R2-MTX regimen (Rituximab 375mg/m2 IV d0, methotrexate 3.5g/m2 civ d1, lenalidomide 15-25mg d1-14, 21 days per cycle) as induction regimen.The dose of rituximab and methotrexate is fixed dose. This is a 3+3 design Ib phase dose-escalation study to determined the maximum tolerated dose(MTD) of lenalidomide dose in combined regimen. 3 levels of lenalidomide dose will be investigated, 15mg, 20mg and 25mg. If the DLT is not found, the dose of 25mg qd will be used for phase II trial.
[update 02-Jun-2020:the recommended phase II doses is 25mg d1-14]
Step 2 is a single-arm phase 2 study with fixed does of R2-MTX regimen in newly-diagnosed PCNSL patients. The response will be evaluated every 2 cycles. Patients who achieved complete remission (CR) or partial remission (PR) will receive further treatment, and there are 6 cycles of R2-MTX regimen for the induction. The patients with stable disease (SD) or progressed disease (PD) will withdraw from the trial and receive salvage regimens. After total 6 induction cycles, the investigators evaluate the efficiency again, the patients with CR or PR will go to lenalidomide maintenance for 2 years or until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion. And the patients with SD or PD will receive salvage regimen.
[update 02-Jun-2020:Younger patients(≤60 years) who achieve PR after 6 cycles of induction therapy will be candidates of high-dose chemotherapy and stem cell rescue. Lenalidomide maintenance will be administed after the high-dose chemotherapy. Older patients(>60 years) who achieve PR after 6 cycles of induction will go to lenalidomide maintenance directly.] During following-up, surveillance examination and brain magnetic resonance imaging (MRI) scans can be performed every 3 months up to the first 2 years, followed by doctor visit every 6 months up to 5 years or the disease relapses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| R2-MTX-LEN | Experimental | Drug: Methotrexate, Drug: Rituximab, Drug: LenalidomidePhase Ib:Experimental arm will be treated with R2-MTX regimen for 6 cycles as initiate induction, the dose of lenalidomide was escalated from 15mg, 20mg, 25mg to test DLT by 3+3 design, meanwhile the dose of rituximab and methotrexate is fixed. If the patients achieved CR or PR by MRI and CSF evaluation, they processed to lenalidomide maintenance for 2 years. Phase II: the patients will be treated by fixed dose of R2-MTX regimen (established lenalidomide dose from phase Ib study) for 6 cycles. the efficiency evaluation will be performed every 2 cycles, the patients who achieved CR or PR will finish the total 6 cycles of induction therapy, then begin the stage of lenalidomide maintenance for 2 years. Follow-ups should be taken for 5 years. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Newly-diagnosed primary vitreoretinal lymphoma
- ECOG≤2
- creatinine clearance rate (CCR) ≥ 50ml/h, according to Cockcroft-Gault
- Total bilirubin < 2 upper limits of normal, alanine aminotransferase(ALT) < 3 upper limits of normal
- HIV-Ab negative
Key exclusion criteria (5 listed)
- Pre-existing uncontrolled active infection
- Clinical evidence of grade 3 or 4 heart failure as defined by the New York Heart Association criteria
- systemic lymphoma involved CNS
- Pregnancy or active lactation
- Co-existing tumors
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 |
|---|---|---|
| Methotrexate3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol | Drug | R2-MTX-LEN |
| Rituximab375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol | Drug | R2-MTX-LEN |
| LenalidomideIn phase 1b study, a 3+3 design dose- escalation will be taken. 3 levels should be tested, 15/20/25mg orally d1-14, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol. [update 02-Jun-2020: the phase Ib trial has finished,and no MDT was obsevered in 25mg group. So the recommanded phase II dose was 25mg.] In phase II study, 25mg daily is considered as an experiment dose for the induction cycles. In both phase Ib and II study, the does of lenalidomide maintenance is fixed to 25mg orally d1-21 every 28 days for 1 cycle. The duration of maintenance is 2 years. | Drug | R2-MTX-LEN |
Primary outcome
2 years progression-free survival
Time frame: From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow-up without relapsing
2 secondary outcomes
2 years overall survival
Time frame: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
dose-limiting toxicity(DLT)
Time frame: from the start of the first dose of lenalidomide to the finish of first cycle of induction(21 days for each cycle).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2020.
- 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.
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 Methotrexate, Rituximab and Lenalidomide in people with Primary Central Nervous System Lymphoma, run by Peking Union Medical College Hospital at 1 site in China.
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 8 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 5 Jun 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2 years progression-free survival (time frame: From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years). 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 5 Jun 2020.