Clinical trial · Interventional
A Dose-escalating Pilot Study of Orelabrutinib for Newly-diagnosed PCNSL
A Dose-escalating Pilot Study of Orelabrutinib in Combination With Rituximab, Methotrexate and Dexamethasone for Newly-diagnosed Primary Central Nervous System Lymphoma
NCT05036577CI-TRIAL-00122809ORMD2021completedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Primary Central Nervous System Lymphoma | Primary Central Nervous System Lymphoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Dexamethasone | Drug | Dexamethasone | ALIAS |
| Methotrexate (MTX) | Drug | Methotrexate | ALIAS |
| Orelabrutinib | Drug | — | UNRESOLVED |
| Rituximab | Drug | Rituximab | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- ORMD (Orelabrutinib, Rituximab, Methotrexate and Dexamethasone)
- description
- 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.
- interventionNames
- Drug: Orelabrutinib
- Drug: Rituximab
- Drug: Methotrexate (MTX)
- Drug: Dexamethasone
Primary outcomes (1)
- measure
- define the Maximum tolerated dose (MTD) contour of Orelabrutinib and MTX
- timeFrame
- From the start of the first dose of Orelabrutinib to the end of the first cycle of induction treatment (21 days/cycle)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
Inclusion Criteria: * 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. Exclusion Criteria: * 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 * 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
References
Publications (0)
Data not yet available
No reference posted for this study.