Primary Central Nervous System LymphomaPhase 1ORMD2021NCT05036577
A Dose-escalating Pilot Study of Orelabrutinib for Newly-diagnosed PCNSL
A Phase 1 study testing Orelabrutinib, Rituximab and Methotrexate (MTX) in people with Primary Central Nervous System Lymphoma, run by Huashan Hospital at 1 site in China.
Trial summary
This is a single arm, single center, open label pilot study of Orelabrutinib combined with Rituximab, high-dose (HD) Methotrexate and Dexamethasone in newly-diagnosed primary central nervous system lymphpoma (PCNSL). 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?
- Orelabrutinib, Rituximab and Methotrexate (MTX)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteChina
- Study dates
- 10 Oct 2021to 30 Mar 2025
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- anti-neoplasm systemic treatement naive primary central nervous system lymphoma
- Pathological type is diffuse large B cell lymphoma
- Enough residual sample of tumor after pathological diagnosis
- ECOG =<3
- Life expectancy >3 months
- Adequate organ function and adequate bone marrow reserve
- Must be able to tolerate lumbar puncture and/or have Omaya tube
- Participant or his/her legal agent must be willing to sign a written informed consent document.
Who cannot join
- Lymphoma invading outside CNS
- Lymphoma only existed in vitreo-retina
- Severe or uncontrolled cardiovascular disease
- Active hemorrhage within 2 months prior screening
- Cerebral ischemic stroke or bleeding within 6 months prior screening
- Organ transplantation or allogeneic hematopoietic stem cell transplantation history
Show all 21Show fewer
- Other surgery history within 6 weeks prior screening
- Anti-tumor herbal medicine treatment within 4 weeks prior screening
- Activated or uncontrolled hepatitis virus B infection (HBsAg positive with/or HBc Ab positive and HBV-DNA titration positive), hepatitis virus C antibody positive, HIV positive.
- Uncontrolled active systemic fungal, bacterial, virus or other microbe infection, or intravenous injection of antibiotics needed
- Accepted live vaccine or immunization within 4 weeks prior eligibility
- Continuously taking drugs with medium / strong inhibition or induction of cytochrome P450 CYP3A is needed
- Allergy to orelabrutinib or the subsidiary (or supplementary) material (Hydroxypropyl methylcellulose acetate succinate, mannitol, cross-linked sodium carboxymethylcellulose, hydroxypropyl cellulose, silica and magnesium stearate)
- Obvious gastro-bowel disease which may influence the intaking, transportation or absorption of the drug, or total gastrectomy
- Past or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, or drug-related pneumonia, with severe impairment of pulmonary function
- Chronic liver damage, severe fatty liver or alcoholic liver disease
- Intention to undergo autologous stem cell transplantation
- Pregnant or breeding women, or women of childbearing age who are unwilling to take contraceptive measures during the whole study period and within 180 days after the last administration of the study drug; non surgically sterilized men who are unwilling to take contraceptive measures during the whole study period and within 180 days of the last administration of the study drug.
- Potentially life-threatening situation, or severe organ dysfunction, or situations the researchers believe not suitable for the trial
- Any mental or cognitive impairment which may limit the understanding and implementation of informed consent or the compliance with the study.
- previously exposed with WBRT
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Hematology, Huashan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200040
About this study
Official title: A Dose-escalating Pilot Study of Orelabrutinib in Combination With Rituximab, Methotrexate and Dexamethasone for Newly-diagnosed Primary Central Nervous System Lymphoma
This is a single arm, single center, open label pilot study of Orelabrutinib combined with Rituximab, high-dose (HD) Methotrexate and Dexamethasone in newly-diagnosed primary central nervous system lymphpoma (PCNSL). The purpose is to evaluate the safety and to find the optimal dose of Orelabrutinib and Methotrexate in this combination treatment for newly-diagnosed PCNSL patients.
Read the detailed description
The eligible patients will be treated with Orelabrutinib combined with Rituximab, high-dose Methotrexate and Dexamethasone during induction treatment (6-8 cycles; 21 days/cycle): Rituximab 375 mg/m2, intravenous infusion, d1; HD-MTX 3.5 g/m2 intravenous infusion (3h), d2; Dexamethasone 10-15 mg, iv, d1-4. Orelabrutinib will be given 72h after MTX infusion or until MTX clearance. The study will investigate optimal dose combination of Orelabrutinib and MTX implementing BOIN waterfall design. The starting dose of Orelabrutinib is 150 mg/d and the dose will be escalated to 200 mg/d, throughout the whole cycle. Meanwhile, the starting dose of MTX is 3g/m2 and will be escalated to 5g/m2, throughout induction phase. Dose escalation and movement in dose matrix will be determined by BOIN algorithm. For CR/CRu patients after completion of induction treatment, daily Orelabrutinib will be administered as maintenance treatment for up to 1 year or until disease progression, intolerable toxicity, death, informed consent withdrawal or lost of follow up (whichever occurs first). Patients will be evaluated every 2 cycles during induction therapy and every 12 weeks during maintenance therapy.
- Conditions
- Primary Central Nervous System Lymphoma
- Being tested
- Orelabrutinib, Rituximab, Methotrexate (MTX), Dexamethasone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OrelabrutinibDrug
Orelabrutinib will be given as 150 mg/d or 200 mg/d orally 72h after MTX infusion or MTX clearance, every 21 days for 6-8 cycles during combination induction treatment.
Daily Orelabrutinb with dose in last cycle of induction will be administered as maintenance treatment for up to 1 year or until disease progression, intolerable toxicity, death, informed consent withdrawal or lost of follow up (whichever occurs first).
RituximabDrug
Rituximab 375 mg/m2 intravenous infusion d1, every 21 days for 6-8 cycles during combination induction treatment.
Methotrexate (MTX)Drug
high-dose Methotrexate 3.5 g/m2 or 5g/m2 intravenous infusion (3h) d2, every 21 days for 6-8 cycels during combination induction treatment.
DexamethasoneDrug
Dexamethasone 10-15 mg, iv, d1-4, every 21 days for 6-8 cycles during combination induction treatment.
| Study group | Role | What they receive |
|---|---|---|
| ORMD (Orelabrutinib, Rituximab, Methotrexate and Dexamethasone) | Experimental | Patients were treated for 6-8 cycles of induction therapy with 21 days per cycle, receiving rituximab (375mg/m2 on day 1), dexamethasone (10-15mg on d1-d4), MTX (d2, 3.5g/m2 or 5g/m2), and orelabrutinib (once daily, after MTX clearance, 150mg/d, or 200mg/d), followed by orelabrutinib maintenance up to one year among CR/CRu patients or until disease progression, intolerable toxicity, death, informed consent withdrawal or lost of follow up (whichever occurs first). The primary objective was to determine the maximum tolerated dose (MTD) of the combination of orelabrutinib and MTX with R and D and investigate the safety and tolerability of this regimen using Bayesian Optimal Interval (BOIN) waterfall design to determine rule of dose escalation and movement among dose combination matrix to identify MTD contour. Receives: Drug: Orelabrutinib; Drug: Rituximab; Drug: Methotrexate (MTX); Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
define the Maximum tolerated dose (MTD) contour of Orelabrutinib and MTX
A BOIN waterfall design will be employed. Two dose levels of Orelabrutinib (dose level 1: 150 mg/d, dose level 2: 200 mg/d) and two dose levels of MTX (dose level 1: 3.5g/m2, dose level 2: 5g/m2) will be investigated, generating 4 dose combination. DLT was defined by the occurrence of severe toxicities during the first cycle: any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia with hemorrhage, or any grade 3 non-hematologic toxicity that failed to respond to supportive therapy and possibly related to orelabrutinib and/or MTX (assessed according to NCI CTCAE V5.0)
Measured: From the start of the first dose of Orelabrutinib to the end of the first cycle of induction treatment (21 days/cycle)
Secondary outcomes (7)
ORRi
ORRi is defined as the proportion of patients with a best response of CR, CRu or PR during induction therapy
Measured: At the end of cycle 6-8 (each cycle is 21 days)
CRi
CRi is defined as the proportion of patients with a best response of CR or CRu during induction treatment
Measured: At the end of cycle 6-8 (each cycle is 21 days)
TTR
Time to response during induction therapy
Measured: At the end of cycle 6-8 (each cycle is 21 days)
ORRm
ORRm is defined as the proportion of patients with a best response of CR, CRu or PR during maintenance therapy
Measured: At the end of completion of 1 year of maintenance treatment
CRm
CRm is defined as the proportion of patients with a best response of CR or CRu during maintenance therapy
Measured: At the end of completion of 1 year of maintenance treatment
Progression-free survival
Progression-free survival is calculated from the date of start of therapy until the date of first documented progress or death due to any cause.
Measured: Up to 2 years
Overall survival
Overall survival is defined as the duration from start of treatment to time of death.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start10 Oct 2021
- Primary completion31 Dec 2023
- Study completion30 Mar 2025
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 Huashan 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Huashan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tong Chen, MD, Huashan Hospital
- Investigators
- Tong Chen, Principal investigator, Huashan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05036577
- Sponsor's protocol ID
- KY2021-726
- Acronym
- ORMD2021
- Status last verified
- Aug 2026
- First submitted
- 27 Aug 2021
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose-escalating Pilot Study of Orelabrutinib in Combination With Rituximab, Methotrexate and Dexamethasone for Newly-diagnosed Primary Central Nervous System Lymphoma
- ClinicalTrials.gov ID
- NCT05036577
- Acronym / sponsor ID
- ORMD2021 / KY2021-726
- Conditions
- Primary Central Nervous System Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Huashan HospitalUniversity, hospital or other
- Study start
- 10 Oct 2021 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 30 Mar 2025 (actual)
- First posted
- 5 Sep 2021 (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 single arm, single center, open label pilot study of Orelabrutinib combined with Rituximab, high-dose (HD) Methotrexate and Dexamethasone in newly-diagnosed primary central nervous system lymphpoma (PCNSL). The purpose is to evaluate the safety and to find the optimal dose of Orelabrutinib and Methotrexate in this combination treatment for newly-diagnosed PCNSL patients.
Detailed description
The eligible patients will be treated with Orelabrutinib combined with Rituximab, high-dose Methotrexate and Dexamethasone during induction treatment (6-8 cycles; 21 days/cycle): Rituximab 375 mg/m2, intravenous infusion, d1; HD-MTX 3.5 g/m2 intravenous infusion (3h), d2; Dexamethasone 10-15 mg, iv, d1-4. Orelabrutinib will be given 72h after MTX infusion or until MTX clearance. The study will investigate optimal dose combination of Orelabrutinib and MTX implementing BOIN waterfall design. The starting dose of Orelabrutinib is 150 mg/d and the dose will be escalated to 200 mg/d, throughout the whole cycle. Meanwhile, the starting dose of MTX is 3g/m2 and will be escalated to 5g/m2, throughout induction phase. Dose escalation and movement in dose matrix will be determined by BOIN algorithm. For CR/CRu patients after completion of induction treatment, daily Orelabrutinib will be administered as maintenance treatment for up to 1 year or until disease progression, intolerable toxicity, death, informed consent withdrawal or lost of follow up (whichever occurs first). Patients will be evaluated every 2 cycles during induction therapy and every 12 weeks during maintenance therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ORMD (Orelabrutinib, Rituximab, Methotrexate and Dexamethasone) | Experimental | Drug: Orelabrutinib, Drug: Rituximab, Drug: Methotrexate (MTX), Drug: DexamethasonePatients were treated for 6-8 cycles of induction therapy with 21 days per cycle, receiving rituximab (375mg/m2 on day 1), dexamethasone (10-15mg on d1-d4), MTX (d2, 3.5g/m2 or 5g/m2), and orelabrutinib (once daily, after MTX clearance, 150mg/d, or 200mg/d), followed by orelabrutinib maintenance up to one year among CR/CRu patients or until disease progression, intolerable toxicity, death, informed consent withdrawal or lost of follow up (whichever occurs first). The primary objective was to determine the maximum tolerated dose (MTD) of the combination of orelabrutinib and MTX with R and D and investigate the safety and tolerability of this regimen using Bayesian Optimal Interval (BOIN) waterfall design to determine rule of dose escalation and movement among dose combination matrix to identify MTD contour. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- anti-neoplasm systemic treatement naive primary central nervous system lymphoma
- Pathological type is diffuse large B cell lymphoma
- Enough residual sample of tumor after pathological diagnosis
- ECOG =<3
- Life expectancy >3 months
Key exclusion criteria (21 listed)
- Lymphoma invading outside CNS
- Lymphoma only existed in vitreo-retina
- Severe or uncontrolled cardiovascular disease
- Active hemorrhage within 2 months prior screening
- Cerebral ischemic stroke or bleeding within 6 months prior screening
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 |
|---|---|---|
| OrelabrutinibOrelabrutinib will be given as 150 mg/d or 200 mg/d orally 72h after MTX infusion or MTX clearance, every 21 days for 6-8 cycles during combination induction treatment. Daily Orelabrutinb with dose in last cycle of induction will be administered as maintenance treatment for up to 1 year or until disease progression, intolerable toxicity, death, informed consent withdrawal or lost of follow up (whichever occurs first). | Drug | ORMD (Orelabrutinib, Rituximab, Methotrexate and Dexamethasone) |
| RituximabRituximab 375 mg/m2 intravenous infusion d1, every 21 days for 6-8 cycles during combination induction treatment. | Drug | ORMD (Orelabrutinib, Rituximab, Methotrexate and Dexamethasone) |
| Methotrexate (MTX)high-dose Methotrexate 3.5 g/m2 or 5g/m2 intravenous infusion (3h) d2, every 21 days for 6-8 cycels during combination induction treatment. | Drug | ORMD (Orelabrutinib, Rituximab, Methotrexate and Dexamethasone) |
| DexamethasoneDexamethasone 10-15 mg, iv, d1-4, every 21 days for 6-8 cycles during combination induction treatment. | Drug | ORMD (Orelabrutinib, Rituximab, Methotrexate and Dexamethasone) |
Primary outcome
define the Maximum tolerated dose (MTD) contour of Orelabrutinib and MTX
Time frame: From the start of the first dose of Orelabrutinib to the end of the first cycle of induction treatment (21 days/cycle)
A BOIN waterfall design will be employed. Two dose levels of Orelabrutinib (dose level 1: 150 mg/d, dose level 2: 200 mg/d) and two dose levels of MTX (dose level 1: 3.5g/m2, dose level 2: 5g/m2) will be investigated, generating 4 dose combination. DLT was defined by the occurrence of severe toxicities during the first cycle: any grade 4 hematologic toxicity, grade 3 febrile neutropenia and grade 3 thrombocytopenia with hemorrhage, or any grade 3 non-hematologic toxicity that failed to respond to supportive therapy and possibly related to orelabrutinib and/or MTX (assessed according to NCI CTCAE V5.0)
7 secondary outcomes
ORRi
Time frame: At the end of cycle 6-8 (each cycle is 21 days)
CRi
Time frame: At the end of cycle 6-8 (each cycle is 21 days)
TTR
Time frame: At the end of cycle 6-8 (each cycle is 21 days)
ORRm
Time frame: At the end of completion of 1 year of maintenance treatment
CRm
Time frame: At the end of completion of 1 year of maintenance treatment
Progression-free survival
Time frame: Up to 2 years
Overall survival
Time frame: Up to 2 years
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 19 Aug 2026.
- 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.
Tong Chen principal investigator
Huashan Hospital
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 Orelabrutinib, Rituximab and Methotrexate (MTX) in people with Primary Central Nervous System Lymphoma, run by Huashan 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 21 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 19 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 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 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?
define the Maximum tolerated dose (MTD) contour of Orelabrutinib and MTX (time frame: From the start of the first dose of Orelabrutinib to the end of the first cycle of induction treatment (21 days/cycle)). 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 19 Aug 2026.