Primary Central Nervous System Lymphoma (PCNSL)Phase 1NCT04688151
Rituximab, Acalabrutinib, and Durvalumab (RAD) in Primary CNS Lymphoma.
A Phase 1 study testing Rituximab in people with Primary Central Nervous System Lymphoma (PCNSL), run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
Trial summary
To evaluate the safety and tolerability and determine the recommended phase 2/phase 3 dose of RAD regimen in PCNSL Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Primary Central Nervous System Lymphoma (PCNSL)
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteTaiwan
- Study dates
- 22 Feb 2021to 31 Dec 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female or male, 20 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
- Histologically or cytologically proven diagnosis of primary CNS lymphomas of large B-cell type in one of the following clinical status:
- Fail to achieve optimal response (CR or PR) after at least one prior therapy with all the toxicities recovered to grade 1 or less from the prior therapy.
- Has confirmed disease relapse or disease progression after at least one prior therapy with all the toxicities recovery to grade 1 or less from the prior therapy.
- Intolerable to the prior therapy because of toxicities with all the toxicities recovery to grade 1 or less from the prior therapy.
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- Treatment naïve but unable or not willing to receive high-dose methotrexate-based induction chemotherapy.
- Have at least one measurable brain parenchymal lesion that can be measured by brain MR or CT images.
- Have adequate organ functions as defined by the following criteria:
- Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≦3 x upper limit of normal (ULN).
- Total serum bilirubin ≦2 x ULN (except for Gilbert's syndrome)
- Absolute neutrophil count (ANC) ≧1,000/mL; Platelets ≧50,000/mL; Hemoglobin≧8.0 g/dL.
- Serum creatinine ≦2.0 x ULN.
- Prothrombin time/International normalized ratio (PT/INR) ≦2.0 x ULN and partial thromboplastin time (PTT) ≦2.0 x ULN.
- Any major surgery must have been completed at least 4 weeks prior to study entry. Any prior therapies, including chemotherapy, rituximab, or high dose or high potency corticosteroids intended to treat lymphoma (dose higher than 100 mg hydrocortisone per day or equivalent potency), must have been completed at least 2 weeks prior to the study entry. However, low-dose, low-potency steroids (ie, up to 100 mg hydrocortisone per day or equivalent potency) may be used prior to the initiation of the trial therapy for the relief of lymphoma-related symptoms. Non-regular steroid administration for premedication purpose are allowed (refer to section 7.7). Any prior radiation performed with curative (i.e., not only palliative) intent or minor surgeries/procedures must have been completed at least 2 weeks prior to the initiation of study medication. Palliative radiation (≤10 fractions) must have been completed 48 hours prior the start of the trial therapy commencing. Any acute toxicity must have been recovered to grade 1 (except alopecia).
- Life expectancy ≥12 weeks in the opinion of the investigator.
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrolment.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, tissue, CSF, and blood sample collections for explorative objectives and other study procedures.
- Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for 12 months after the last dose of RAD or at least 2 days after the last dose of aclabrutinib monotherapy, if the patient receives acalabrutinib monotherapy for greater than 12 months after the last dose of RAD administration. A patient is of childbearing potential if he/she is biologically capable of having children and is sexually active
Who cannot join
- Diagnosis with secondary CNS lymphoma, i.e. systemic lymphoma with CNS involvement or relapse, or diagnosis with PCNSL but with other non-CNS, systemic involvement.
- Active or uncontrolled autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia.
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
- Patients with any chronic skin condition that does not require systemic therapy.
- Patients with other autoimmune or inflammatory disorders that are not active in the last 2 years may be included.
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- Patients with celiac disease controlled by diet alone.
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of the trial therapy and of low potential risk for recurrence.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Has positive HBV surface antigen (HBsAg) result. Patients who are negative for HBsAg but are positive for anti-HBc antibody are allowed to be enrolled if their HBV-DNA test are negative.
- Has positive HCV-RNA result.
- Has positive anti-human immunodeficiency virus (HIV)-1/2 antibody test results.
- Prior history of anaphylaxis or severe allergic reactions to anyone of the study drugs or the excipients.
- Prior exposures to checkpoint inhibitors or BTK inhibitors.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of the trial therapy. Note: Patients, if enrolled, should not receive live vaccine while receiving the trial therapy and up to 30 days after the last dose of the trial therapy.
- Has active infection, as ascertained by the investigator, which might result in extra-risk of toxicities with the administration of the trial therapy.
- Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. Participation in another clinical study with the last investigational therapy administration must be finished at least 4 weeks ago before initiating the current RAD trial therapy.
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
- Previous allogeneic hematopoietic stem cell transplant.
- Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
- Known history of drug or alcohol abuse within 2 years of screening.
- Any concomitant medications that are known to be associated with Torsades de Pointes or requires treatments with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.
- For women only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding.
- Has history of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3 to 4), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
- Has current active bleeding disorders or has history of bleeding diathesis.
- Requires warfarin or Vit. K antagonist administration.
- Has history of myocardial infarction.
- Has recent history of vascular stroke or CNS haemorrhagic stroke within 6 months.
- Has confirmed or suspected progressive multifocal leukoencephalopathy
- Has difficulty in swallowing oral medications or has significant gastrointestinal diseases that would limit the absorption of oral medications.
- Has clinically significant cardiac diseases as defined by New York Association Classification class 3 or 4.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib, Multi-center Study of Combining Rituximab, Acalabrutinib, and Durvalumab (RAD) in Primary Central Nervous System Lymphoma.
To evaluate the safety and tolerability and determine the recommended phase 2/phase 3 dose of RAD regimen in PCNSL
Read the detailed description
Target subject population Male and female patients with PCNSL who have failed to achieve a response or who have relapsed after prior therapy (R/R) or who are treatment naïve but are not candidates of standard high-dose methotrexate-based induction chemotherapy. Patients are not to have been previously treated with immune checkpoint inhibitors or Bruton tyrosine kinase (BTK) inhibitors; prior treatment with rituximab is allowed.
Duration of treatment Rituximab will be administered for up to 8 cycles or until intolerance or excessive toxicities relevant to the trial therapy, or withdrawal of consents; acalabrutinib and durvalumab will be continued until disease progression, intolerance, or excessive toxicities relevant to the trial therapy, or withdrawal of consents.
Investigational product, dosage, and mode of administration Dose level 1 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO once every day Durvalumab 1500mg infusion once every 4 weeks Dose level 2 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO twice every day Durvalumab 1500mg infusion once every 4 weeks Expansion Determined by the result of the dose escalation phase Statistical methods
This study will use the 3+3 design in the dose escalation phase. Analyses will be primarily descriptive in nature; no formal statistical hypothesis testing will be performed. The populations used for analysis will include the following:
Safety analysis set: patients who receive at least 1 dose of anyone of the study drugs will be used for safety analyses.
- Being tested
- Rituximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Acalabrutinib, Durvalumab
Dose level 1:Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO once every day Durvalumab 1500mg infusion once every 4 weeks Dose level 2:Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO twice every day Durvalumab 1500mg infusion once every 4 weeks Expansion:Determined by the result of the dose escalation phase
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1,Dose level 2 | Experimental | Dose level 1 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO once every day Durvalumab 1500mg infusion once every 4 weeks Dose level 2 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO twice every day Durvalumab 1500mg infusion once every 4 weeks Receives: Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of acalabrutinib
Dose-limiting toxicity (DLT) patients will be enrolled in cohort of 2 to receive escalating dose of acalabrutinib at two dose levels (level I 100mg PO once , level II 100mg PO twice every day) or more of defined events
Measured: From date of registration until the date of definition of MTD of first documented progression or date of death from any cause, whichever came first, assessed up to 28 weeks.
Secondary outcomes (1)
Tumor response
Efficacy evaluation: objective tumor response according to International PCNSL Collaborative Group Guidelinefor Response Assessment
Measured: From date of registration until the date of definition of MTD of first documented progression or date of death from any cause, whichever came first, assessed up to 28 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2020
- Study start22 Feb 2021
- Primary completion31 Dec 2025
- Study completion31 Dec 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 Lymphoma (PCNSL)Studies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Dose level 1,Dose level 2,3+3 design in the dose escalation.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- National Taiwan University Hospital, National Cheng-Kung University Hospital, China Medical University Hospital, Chang Gung Memorial Hospital
- Responsible party
- Sponsor
- Investigators
- Shang-Ju Wu, M.D, Principal investigator, National Taiwan University Hospital, Taipei, TaiwanSu-Peng Yeh, M.D, Principal investigator, China Medical University HospitalKwang-Yu Chang, M.D, Principal investigator, National Cheng Kung University Hospital,TaiwanMing Chung Wang, M.D, Principal investigator, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04688151
- Sponsor's protocol ID
- T2420
- Status last verified
- Sep 2026
- First submitted
- 8 Dec 2020
- Last updated
- 17 Sep 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 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib, Multi-center Study of Combining Rituximab, Acalabrutinib, and Durvalumab (RAD) in Primary Central Nervous System Lymphoma.
- ClinicalTrials.gov ID
- NCT04688151
- Acronym / sponsor ID
- T2420
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- National Taiwan University Hospital, National Cheng-Kung University Hospital, China Medical University Hospital, Chang Gung Memorial Hospital
- Study start
- 22 Feb 2021 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 29 Dec 2020 (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.
To evaluate the safety and tolerability and determine the recommended phase 2/phase 3 dose of RAD regimen in PCNSL
Detailed description
Target subject population Male and female patients with PCNSL who have failed to achieve a response or who have relapsed after prior therapy (R/R) or who are treatment naïve but are not candidates of standard high-dose methotrexate-based induction chemotherapy. Patients are not to have been previously treated with immune checkpoint inhibitors or Bruton tyrosine kinase (BTK) inhibitors; prior treatment with rituximab is allowed.
Duration of treatment Rituximab will be administered for up to 8 cycles or until intolerance or excessive toxicities relevant to the trial therapy, or withdrawal of consents; acalabrutinib and durvalumab will be continued until disease progression, intolerance, or excessive toxicities relevant to the trial therapy, or withdrawal of consents.
Investigational product, dosage, and mode of administration Dose level 1 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO once every day Durvalumab 1500mg infusion once every 4 weeks Dose level 2 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO twice every day Durvalumab 1500mg infusion once every 4 weeks Expansion Determined by the result of the dose escalation phase Statistical methods
This study will use the 3+3 design in the dose escalation phase. Analyses will be primarily descriptive in nature; no formal statistical hypothesis testing will be performed. The populations used for analysis will include the following:
Safety analysis set: patients who receive at least 1 dose of anyone of the study drugs will be used for safety analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Dose level 1,Dose level 2,3+3 design in the dose escalation.
| Arm | Type | Receives |
|---|---|---|
| Dose level 1,Dose level 2 | Experimental | Drug: RituximabDose level 1 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO once every day Durvalumab 1500mg infusion once every 4 weeks Dose level 2 Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO twice every day Durvalumab 1500mg infusion once every 4 weeks |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Female or male, 20 years of age or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3.
- Histologically or cytologically proven diagnosis of primary CNS lymphomas of large B-cell type in one of the following clinical status:
- Fail to achieve optimal response (CR or PR) after at least one prior therapy with all the toxicities recovered to grade 1 or less from the prior therapy.
- Has confirmed disease relapse or disease progression after at least one prior therapy with all the toxicities recovery to grade 1 or less from the prior therapy.
Key exclusion criteria (33 listed)
- Diagnosis with secondary CNS lymphoma, i.e. systemic lymphoma with CNS involvement or relapse, or diagnosis with PCNSL but with other non-CNS, systemic involvement.
- Active or uncontrolled autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia.
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
- Patients with any chronic skin condition that does not require systemic therapy.
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 |
|---|---|---|
| RituximabAlso: Acalabrutinib, DurvalumabDose level 1:Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO once every day Durvalumab 1500mg infusion once every 4 weeks Dose level 2:Rituximab 375mg/m2 infusion once every 4 weeks for 8 cycles Acalabrutinib 100mg PO twice every day Durvalumab 1500mg infusion once every 4 weeks Expansion:Determined by the result of the dose escalation phase | Drug | Dose level 1,Dose level 2 |
Primary outcome
MTD of acalabrutinib
Time frame: From date of registration until the date of definition of MTD of first documented progression or date of death from any cause, whichever came first, assessed up to 28 weeks.
Dose-limiting toxicity (DLT) patients will be enrolled in cohort of 2 to receive escalating dose of acalabrutinib at two dose levels (level I 100mg PO once , level II 100mg PO twice every day) or more of defined events
1 secondary outcome
Tumor response
Time frame: From date of registration until the date of definition of MTD of first documented progression or date of death from any cause, whichever came first, assessed up to 28 weeks.
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 17 Sep 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.
Shang-Ju Wu, M.D principal investigator
National Taiwan University Hospital, Taipei, Taiwan
Su-Peng Yeh, M.D principal investigator
China Medical University Hospital
Kwang-Yu Chang, M.D principal investigator
National Cheng Kung University Hospital,Taiwan
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 Rituximab in people with Primary Central Nervous System Lymphoma (PCNSL), run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
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 19 inclusion and 33 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 17 Sep 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 Taiwan. 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?
MTD of acalabrutinib (time frame: From date of registration until the date of definition of MTD of first documented progression or date of death from any cause, whichever came first, assessed up to 28 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 17 Sep 2026.