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

Study Purpose

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 in this combination treatment for newly-diagnosed PCNSL patients.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 70 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Newly-diagnosed primary central nervous system lymphoma.
  • - Pathological type is diffuse large B cell lymphoma.
  • - Enough residual sample of tumor after pathological diagnosis.
  • - Measurable tumor lesion (minimal 10mm * 10mm) on brain MRI or CT scan during 28 days before the screening.
  • - 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05036577
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Huashan Hospital
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Tong Chen
Principal Investigator Affiliation Huashan Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Primary Central Nervous System Lymphoma
Additional Details

The eligible patients will be treated with Orelabrutinib combined with Rituximab, high-dose Methotrexate and Dexamethasone during induction treatment (6 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, d2-4. Orelabrutinib will be given 72h after MTX infusion or until MTX clearance. Orelabrutinib dose escalation will follow the "3+3" design. The starting dose of Orelabrutinib is 150 mg/d and the dose will be escalated to 200 mg/d, throughout the whole cycle. 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.

Arms & Interventions

Arms

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

The eligible patients will be treated with Orelabrutinib in combined with Rituximab, high-dose Methotrexate and Dexamethasone during induction treatment (6 cycles; 21 days/cycle). Orelabrutinib dose escalation will follow the "3+3" design. The starting dose of Orelabrutinib is 150 mg/d and the dose will be escalated to 200 mg/d, throughout the whole cycle. CR/CRu patients after induction treatment will continue Orelabrutinib maintenance 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.

Interventions

Drug: - Orelabrutinib

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 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: - Rituximab

Rituximab 375 mg/m2 intravenous infusion d1, every 21 days for 6 cycles during combination induction treatment.

Drug: - Methotrexate (MTX)

high-dose Methotrexate 3.5 g/m2 intravenous infusion (3h) d2, every 21 days for 6 cycels during combination induction treatment.

Drug: - Dexamethasone

Dexamethasone 10-15 mg, iv, d2-4, every 21 days for 6 cycles during combination induction treatment.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Shanghai, Shanghai, China

Status

Recruiting

Address

Department of Hematology, Huashan Hospital, Fudan University

Shanghai, Shanghai, 200040

Site Contact

Tong Chen

chentong@fudan.edu.cn

+862152887102

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