Primary Central Nervous System LymphomaRM-MA-PD1NCT07764601
R-MA-PD-1 Versus R-MA in Treatment-naive Primary CNS Lymphoma
A study testing Penpulimab, Rituximab and Methotrexate in people with Primary Central Nervous System Lymphoma and Diffuse Large B-Cell Lymphoma, run by WEI XU at 5 sites in China.
Trial summary
This is a prospective, open-label, multicenter, randomized controlled study in treatment-naive patients with primary central nervous system lymphoma (PCNSL, DLBCL type). Eligible participants are randomized 1:1 to the experimental arm (R-MA-PD-1: rituximab, methotrexate, cytarabine plus penpulimab) or the control arm… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Primary Central Nervous System Lymphoma, Diffuse Large B-Cell Lymphoma
- What is being tested?
- Penpulimab, Rituximab and Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 5 sitesChina
- Study dates
- Aug 2026to Aug 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fully understands the study and voluntarily signs informed consent.
- Age 18 to 80 years.
- Treatment-naive, pathologically (immunophenotypically) confirmed PCNSL (per 2016 WHO classification).
- Diffuse large B-cell lymphoma originating in the CNS without other organ involvement, confirmed by PET-CT or contrast-enhanced CT.
- Expected survival more than 3 months.
- Laboratory: creatinine clearance ≥50 mL/min (Cockcroft-Gault); INR ≤1.5 x ULN or aPTT ≤1.5 x ULN (INR 2-3 allowed if on warfarin); LVEF ≥50%.
- GFR ≥60 mL/min.
- Participants of childbearing potential must agree to use effective contraception during the study and for 30 days after the last dose.
Who cannot join
- Contraindication to any study drug.
- Clinically significant liver disease, including viral or other hepatitis or cirrhosis (active HBV or active hepatitis C as defined).
- HIV infection.
- History of allergic disease, severe drug allergy, or known hypersensitivity to macromolecular protein preparations or any component of penpulimab.
- Prior anti-PD-1/PD-L1/PD-L2, anti-CTLA-4 antibody, CAR-T, or any other agent targeting T-cell co-stimulation or checkpoint pathways.
- Congestive heart failure (NYHA >2); acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months.
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- Congenital long QT syndrome or QTcF >480 ms.
- Other malignancy within the past 5 years (except adequately treated in situ cervical carcinoma, basal cell skin carcinoma, in situ breast carcinoma, or a second primary cancer cured and recurrence-free for 5 years).
- Pregnant or lactating women, or intending to become pregnant during the study.
- History of clinically significant neurological or psychiatric disorder, or substance/drug abuse.
- Clinically significant active infection.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
China5 sites
The First People's Hospital of Changzhou
Changzhou, Jiangsu
The First People's Hospital of Huai'an
Huai'an, Jiangsu
The First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu
Wei Xu
Wuxi People's Hospital
Wuxi, Jiangsu
Yixing People's Hospital
Yixing, Jiangsu
About this study
Official title: A Prospective, Open-label, Randomized Controlled Study Comparing Rituximab, Methotrexate, Cytarabine, and Penpulimab (R-MA-PD-1) Versus Rituximab, Methotrexate, and Cytarabine (R-MA) in Treatment-naive Patients With Primary Central Nervous System Lymphoma
This is a prospective, open-label, multicenter, randomized controlled study in treatment-naive patients with primary central nervous system lymphoma (PCNSL, DLBCL type). Eligible participants are randomized 1:1 to the experimental arm (R-MA-PD-1: rituximab, methotrexate, cytarabine plus penpulimab) or the control arm (R-MA: rituximab, methotrexate, cytarabine). Induction is administered every 21 days for 6 cycles, followed by risk- and response-adapted consolidation (ASCT or whole-brain radiotherapy) and penpulimab maintenance. The primary objective is to compare the 2-year progression-free survival rate between the two arms.
Read the detailed description
Primary central nervous system lymphoma is a rare, aggressive non-Hodgkin lymphoma, predominantly diffuse large B-cell lymphoma. High-dose methotrexate-based chemotherapy is the standard induction, but the optimal combination remains to be defined. Building on a prior single-arm phase II study of penpulimab plus R-MA (NCT05347641), this randomized controlled study evaluates whether adding the PD-1 inhibitor penpulimab to R-MA improves efficacy in treatment-naive PCNSL.
Induction (both arms, every 21 days x 6 cycles):
- Rituximab 375 mg/m2 (Day 0)
- Methotrexate 3.5 g/m2 (Day 1)
- Cytarabine (Ara-C): age <60 or ECOG ≤2: 2 g/m2 q12h Day 2-3; age ≥60 or ECOG >2: 1 g/m2 q12h Day 2 (from cycle 2)
- Experimental arm only: Penpulimab 200 mg (Day 5)
Consolidation (response- and age-adapted): patients <60 years achieving PR/CR proceed to autologous stem cell transplantation (thiotepa + busulfan); patients ≥60 years or ASCT-ineligible receive penpulimab maintenance (CR) or whole-brain radiotherapy 36 Gy plus penpulimab maintenance (PR). Experimental-arm responders receive 8 cycles of penpulimab maintenance.
Sample size: 58 participants (29 vs 29), based on 2-year PFS of 39% (R-MA) versus 70% (R-MA-PD-1), two-sided alpha 0.05, power 80%, 18-month enrollment, 30-month follow-up, 10% dropout (PASS 15.0).
- Being tested
- Penpulimab, Rituximab, Methotrexate, Cytarabine
- Keywords
- PCNSL, Penpulimab, PD-1 inhibitor, High-dose methotrexate, Rituximab
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PenpulimabBiological
Anti-PD-1 monoclonal antibody, 200 mg intravenously on Day 5 of each induction cycle; continued as maintenance in responders.
RituximabDrug
375 mg/m2 intravenously on Day 0 of each induction cycle.
MethotrexateDrug
3.5 g/m2 intravenously on Day 1 of each induction cycle.
CytarabineDrug
Age <60 or ECOG ≤2: 2 g/m2 q12h on Days 2-3; age ≥60 or ECOG >2: 1 g/m2 q12h on Day 2 (from cycle 2).
| Study group | Role | What they receive |
|---|---|---|
| R-MA-PD-1 (Experimental) | Experimental | Rituximab 375 mg/m2 (D0), methotrexate 3.5 g/m2 (D1), cytarabine (D2-3 or D2 by age/ECOG), plus penpulimab 200 mg (D5), every 21 days for 6 induction cycles, followed by response- and age-adapted consolidation and penpulimab maintenance. Receives: Biological: Penpulimab; Drug: Rituximab; Drug: Methotrexate; Drug: Cytarabine |
| R-MA (Active Comparator) | Active comparator | Rituximab 375 mg/m2 (D0), methotrexate 3.5 g/m2 (D1), and cytarabine (D2-3 or D2 by age/ECOG), every 21 days for 6 induction cycles, followed by response- and age-adapted consolidation (ASCT or WBRT). Receives: Drug: Rituximab; Drug: Methotrexate; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-year progression-free survival (PFS) rate
PFS is defined as the time from randomization to first documented disease progression or relapse (per 2014 Lugano response criteria) or death from any cause, whichever occurs first, as determined by the investigator.
Measured: 2 years from randomization
Secondary outcomes (5)
Complete response (CR) rate
Proportion of patients with best overall response of CR by PET-CT during induction, per 2014 Lugano criteria.
Measured: From randomization through end of induction (6 cycles of 21 days each; up to 18 weeks)
Objective response rate (ORR)
Proportion of patients with best overall response of PR or CR during induction, per 2014 Lugano criteria.
Measured: From randomization through end of induction (6 cycles of 21 days each; up to 18 weeks)
Overall survival (OS)
Time from randomization to death from any cause.
Measured: Up to 3 years from randomization
Duration of response (DOR)
Time from first documented response to disease progression or death from any cause.
Measured: Up to 3 years from randomization
Incidence of adverse events
Incidence and severity of adverse events graded per CTCAE.
Measured: From first dose until 30 days after last dose (induction 18 weeks + consolidation [ASCT/WBRT] + penpulimab maintenance 24 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2026
- Study startAug 2026 (estimated)
- Primary completionAug 2028 (estimated)
- Study completionAug 2029 (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.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- WEI XU
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, WEI XU, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07764601
- Sponsor's protocol ID
- RM-MA-PD1
- Other IDs
- 2026-SR-532
- Acronym
- RM-MA-PD1
- Status last verified
- Aug 2026
- First submitted
- 6 Aug 2026
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Open-label, Randomized Controlled Study Comparing Rituximab, Methotrexate, Cytarabine, and Penpulimab (R-MA-PD-1) Versus Rituximab, Methotrexate, and Cytarabine (R-MA) in Treatment-naive Patients With Primary Central Nervous System Lymphoma
- ClinicalTrials.gov ID
- NCT07764601
- Acronym / sponsor ID
- RM-MA-PD1 / RM-MA-PD1
- Keywords
- PCNSL, Penpulimab, PD-1 inhibitor, High-dose methotrexate, Rituximab
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- WEI XUUniversity, hospital or other
- Study start
- Aug 2026 (estimated)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 14 Aug 2026 (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 prospective, open-label, multicenter, randomized controlled study in treatment-naive patients with primary central nervous system lymphoma (PCNSL, DLBCL type). Eligible participants are randomized 1:1 to the experimental arm (R-MA-PD-1: rituximab, methotrexate, cytarabine plus penpulimab) or the control arm (R-MA: rituximab, methotrexate, cytarabine). Induction is administered every 21 days for 6 cycles, followed by risk- and response-adapted consolidation (ASCT or whole-brain radiotherapy) and penpulimab maintenance. The primary objective is to compare the 2-year progression-free survival rate between the two arms.
Detailed description
Primary central nervous system lymphoma is a rare, aggressive non-Hodgkin lymphoma, predominantly diffuse large B-cell lymphoma. High-dose methotrexate-based chemotherapy is the standard induction, but the optimal combination remains to be defined. Building on a prior single-arm phase II study of penpulimab plus R-MA (NCT05347641), this randomized controlled study evaluates whether adding the PD-1 inhibitor penpulimab to R-MA improves efficacy in treatment-naive PCNSL.
Induction (both arms, every 21 days x 6 cycles):
- Rituximab 375 mg/m2 (Day 0)
- Methotrexate 3.5 g/m2 (Day 1)
- Cytarabine (Ara-C): age <60 or ECOG ≤2: 2 g/m2 q12h Day 2-3; age ≥60 or ECOG >2: 1 g/m2 q12h Day 2 (from cycle 2)
- Experimental arm only: Penpulimab 200 mg (Day 5)
Consolidation (response- and age-adapted): patients <60 years achieving PR/CR proceed to autologous stem cell transplantation (thiotepa + busulfan); patients ≥60 years or ASCT-ineligible receive penpulimab maintenance (CR) or whole-brain radiotherapy 36 Gy plus penpulimab maintenance (PR). Experimental-arm responders receive 8 cycles of penpulimab maintenance.
Sample size: 58 participants (29 vs 29), based on 2-year PFS of 39% (R-MA) versus 70% (R-MA-PD-1), two-sided alpha 0.05, power 80%, 18-month enrollment, 30-month follow-up, 10% dropout (PASS 15.0).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| R-MA-PD-1 (Experimental) | Experimental | Biological: Penpulimab, Drug: Rituximab, Drug: Methotrexate, Drug: CytarabineRituximab 375 mg/m2 (D0), methotrexate 3.5 g/m2 (D1), cytarabine (D2-3 or D2 by age/ECOG), plus penpulimab 200 mg (D5), every 21 days for 6 induction cycles, followed by response- and age-adapted consolidation and penpulimab maintenance. |
| R-MA (Active Comparator) | Active comparator | Drug: Rituximab, Drug: Methotrexate, Drug: CytarabineRituximab 375 mg/m2 (D0), methotrexate 3.5 g/m2 (D1), and cytarabine (D2-3 or D2 by age/ECOG), every 21 days for 6 induction cycles, followed by response- and age-adapted consolidation (ASCT or WBRT). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Fully understands the study and voluntarily signs informed consent.
- Age 18 to 80 years.
- Treatment-naive, pathologically (immunophenotypically) confirmed PCNSL (per 2016 WHO classification).
- Diffuse large B-cell lymphoma originating in the CNS without other organ involvement, confirmed by PET-CT or contrast-enhanced CT.
- Expected survival more than 3 months.
Key exclusion criteria (11 listed)
- Contraindication to any study drug.
- Clinically significant liver disease, including viral or other hepatitis or cirrhosis (active HBV or active hepatitis C as defined).
- HIV infection.
- History of allergic disease, severe drug allergy, or known hypersensitivity to macromolecular protein preparations or any component of penpulimab.
- Prior anti-PD-1/PD-L1/PD-L2, anti-CTLA-4 antibody, CAR-T, or any other agent targeting T-cell co-stimulation or checkpoint pathways.
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 |
|---|---|---|
| PenpulimabAnti-PD-1 monoclonal antibody, 200 mg intravenously on Day 5 of each induction cycle; continued as maintenance in responders. | Biological | R-MA-PD-1 (Experimental) |
| Rituximab375 mg/m2 intravenously on Day 0 of each induction cycle. | Drug | R-MA (Active Comparator), R-MA-PD-1 (Experimental) |
| Methotrexate3.5 g/m2 intravenously on Day 1 of each induction cycle. | Drug | R-MA (Active Comparator), R-MA-PD-1 (Experimental) |
| CytarabineAge <60 or ECOG ≤2: 2 g/m2 q12h on Days 2-3; age ≥60 or ECOG >2: 1 g/m2 q12h on Day 2 (from cycle 2). | Drug | R-MA (Active Comparator), R-MA-PD-1 (Experimental) |
Primary outcome
2-year progression-free survival (PFS) rate
Time frame: 2 years from randomization
PFS is defined as the time from randomization to first documented disease progression or relapse (per 2014 Lugano response criteria) or death from any cause, whichever occurs first, as determined by the investigator.
5 secondary outcomes
Complete response (CR) rate
Time frame: From randomization through end of induction (6 cycles of 21 days each; up to 18 weeks)
Objective response rate (ORR)
Time frame: From randomization through end of induction (6 cycles of 21 days each; up to 18 weeks)
Overall survival (OS)
Time frame: Up to 3 years from randomization
Duration of response (DOR)
Time frame: Up to 3 years from randomization
Incidence of adverse events
Time frame: From first dose until 30 days after last dose (induction 18 weeks + consolidation [ASCT/WBRT] + penpulimab maintenance 24 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
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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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Penpulimab, Rituximab and Methotrexate in people with Primary Central Nervous System Lymphoma and Diffuse Large B-Cell Lymphoma, run by WEI XU at 5 sites 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 11 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: opening soon, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wei Xu (+86 13951699449, xuwei10000@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-year progression-free survival (PFS) rate (time frame: 2 years from randomization). 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 14 Aug 2026.