A Dose-escalating Pilot Study of Orelabrutinib for Newly-diagnosed PCNSL

Sponsor
Huashan Hospital
Study ID
NCT05036577
Phase
PHASE1
Status
Active Not Recruiting

Conditions

  • Primary Central Nervous System Lymphoma

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Orelabrutinib — DRUG
    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).
  • Rituximab — DRUG
    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.
  • Dexamethasone — DRUG
    Dexamethasone 10-15 mg, iv, d1-4, every 21 days for 6-8 cycles during combination induction treatment.

Study Details

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.

Key Dates

Start date
Oct 10, 2021
Status verified
Oct 2024
Primary completion
Dec 31, 2023
Completion
Sep 30, 2025

Study Design

Enrollment
15 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: ORMD (Orelabrutinib, Rituximab, Methotrexate and Dexamethasone)
    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.

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) ]

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