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Refractory and Relapsed Primary CNS LymphomaPhase 1/2NCT05021770

Orelabrutinib in Combination With Thiotepa in Refractory and Relapsed Primary CNS Lymphoma

A Phase 1/2 study testing Orelabrutinib and Thiotepa in people with Refractory and Relapsed Primary CNS Lymphoma and PCNSL, run by Huiqiang Huang at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study was to investigate the maximum tolerated dose and efficacy of Orelabrutinib combined with Thiotepa in refractory and relapsed primary central nervous system lymphoma (PCNSL). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Orelabrutinib and Thiotepa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteChina
Study dates
Dec 2021to Jun 2024
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men and woman who aged 18 or older on the day of consenting to the study.
  • Participants must be able to understand and willing to sign a written informed consent document.
  • ECOG performance status of 0 to 2.
  • Histologically documented primary central nervous system(CNS) lymphoma.
  • Participants should have evidence of 1 measurable or evaluable enhancing disease on MRI, PET-CT or PET-MRI.
  • Relapsed or refractory disease with at least 1 prior HD-MTX-based therapy.
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  • Life expectancy of > 3 months (in the opinion of the investigator).
  • Any non-hematologic toxicity associated with prior treatment should be stable and recovered to ≤ Grade 1 (according to NCI CTCAE V5.0，except for alopecia)
  • Demonstrate adequate organ function as defined below: (all screening labs should be performed within 14 days of treatment initiation)
  • Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L, Platelets ≥ 75 x 10^9/L，Hb ≥80 g/L;
  • International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 times the upper limit of normal;
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal;
  • Serum bilirubin ≤ 1.5 times the upper limit of normal;
  • Creatinine clearance ≥ 60 mL/min calculated by the Cockcroft-Gault formula using actual body weight.
  • Must be able to tolerate MRI/CT/PET-CT/PET-MRI scans and lumbar puncture.
  • Ability to swallow oral medications.
  • Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
  • If the disease progresses after radiotherapy, there is no need for washout period;If the tumor responds after radiotherapy, a 6-month washout period is required.
  • First-line treatment with thiotepa-containing regimens is effective, and patients who relapse after more than 1 year can be enrolled.

Who cannot join

  • The pathological diagnosis was T-cell lymphoma.
  • Prior therapy with a checkpoint inhibitor or BTK inhibitor.
  • Participation in another clinical study with an investigational product during the 12 weeks prior to the first day of study treatment.
  • Participants requires more than 5 mg of dexamethasone daily or the equivalent for control of primary CNS symptoms lasting for more than 5 days within 14 days.
  • Active bleeding within 4 weeks prior to first administration, or ongoing use of anticoagulant/antiplatelet agents, or tendency to bleeding (e.g., esophageal varices at risk for bleeding, locally active ulcerative lesions) or coagulation disorder as considered by the investigator.
  • Has an uncontrolled or significant cardiovascular disease, including (but not limited to) :
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  • Any of the following conditions within 6 months prior to initial administration: congestive heart failure (NYHA class III or IV), myocardial infarction, unstable angina, or arrhythmia requiring treatment at the time of screening, left ventricular ejection fraction (LVEF) <50%;
  • Primary or secondary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmic right ventricular cardiomyopathy, restricted cardiomyopathy, undefined cardiomyopathy);
  • Clinical history of prolonged QTc phase, grade II type II atrioventricular block or grade III atrioventricular block or QTc interval (F method) \& GT;470 msec (female) or >;480msec (male).
  • Hypertension, which is difficult to control, is not suitable for this study
  • Uncontrolled infections or infections requiring intravenous antimicrobial treatment.
  • Known active infection with hepatitis C virus (HCV)，hepatitis B virus (HBV) or syphilis as determined by serologic tests and/or PCR.
  • History of or positive human immunodeficiency virus (HIV) screen result.
  • Patient underwent major systemic surgery ≤ 6 weeks prior to starting the trial treatment or who has not recovered from the side effects of such surgery, or who plan to have surgery within 2 weeks of the first dose of the study drug.
  • Previous organ transplantation or allogeneic stem cell transplantation.
  • Pregnant or lactating women, or subjects of childbearing age who do not want to use contraception for 180 days from the study period to the end of the study.
  • History of stroke and intracranial hemorrhage within 6 months before the first administration, except intracranial hemorrhage caused by surgical sequelae.
  • Patient with hepatic、renal 、neurological、psychiatric, or endocrine disease , as Investigator's discretion, is too damaged to participate in this study; Patient having other conditions that should exclude it from the trial, as the Investigator's discretion.
  • Alcohol or drug abuse.
  • Allergic to any component of the investigational product.
  • Participants who received live viral vaccination within 4 weeks from enrollment date. Patients are prohibited from receiving live attenuated vaccines, including influenza vaccines, during the study period.
  • Previous CAR-T therapy.
  • PVRL.

Trial locations and contacts

1 site in 1 country.

Huiqiang Huang, Professor contact

+86 020 87343350

huanghq@sysucc.org.cn

China1 site

  • Department of Medical Oncology, Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

    Huiqiang Huang, Professor, +86 020 87343350, huanghq@sysucc.org.cn

    Huiqiang Huang

Other trials in China

About this study

Official title: Safety and Efficacy of Orelabrutinib（O） in Combination With Thiotepa（T） in Refractory and Relapsed Primary CNS Lymphoma： A Single-arm, Multicenter Phase Ib/II Study（OT）

The purpose of this study was to investigate the maximum tolerated dose and efficacy of Orelabrutinib combined with Thiotepa in refractory and relapsed primary central nervous system lymphoma (PCNSL).

Being tested
Orelabrutinib, Thiotepa
Keywords
PCNSL
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OrelabrutinibDrug

    150mg or 200mg orally daily

  • OrelabrutinibDrug

    RP2D

  • ThiotepaDrug

    30 mg/m2 intravenously every 3 weeks (maximum 6 cycle)

Study groups in NCT05021770
Study groupRoleWhat they receive
Phase IbExperimentalOrelabrutinib dose escalation will occur using a standard 3+3 dose-escalation approach to determined the maximum tolerated dose(MTD) of orelabrutinib dose in combined with thiotepa, beginning at dose level I (150 mg daily) and potentially escalating to dose level 2 (200mg) with rules for escalation and de-escalation. If the dose-limiting toxicity is not found, the dose of 200mg will be used for phase II trial (RP2D). Orelabrutinib: 150mg or 200mg orally daily. Thiotepa: The dose of thiotepa is fixed as 30 mg/m2 intravenously every 3 weeks (maximum 6 cycle).
Receives: Drug: Orelabrutinib; Drug: Thiotepa
Phase IIExperimentalParticipants will receive orelabrutinib and thiotepa at the pre-determined dosage level established in Phase 1b, until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion. The response will be evaluated every 2 cycles. Orelabrutinib: RP2D (150 mg or 200 mg qd) Thiotepa:Sintilimab: The dose of thiotepa is fixed as 30 mg/m2 intravenously every 3 weeks (maximum 6 cycle).
Receives: Drug: Orelabrutinib; Drug: Thiotepa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1 Dose Escalation：The maximum tolerated dose (MTD)

    To determine the maximum tolerated dose (MTD)

    Measured: Incidence of dose limiting toxicities (DLTs) up to 21 days

  2. Part 2 Dose Expansion：ORR (Investigator-Assessed)

    The overall response rate (ORR) including complete response (CR), unconfirmed complete (CRu) and partial response (PR) according to the 2005 Response Criteria of the International Primary CNS Lymphoma Collaborative Group (IPCG)

    Measured: Up to 2 years

Secondary outcomes (12)

  1. Part 1 Dose Escalation：Objective response rate (ORR)

    The objective response rate (ORR) is defined as the proportion of patients with a best response of CR, CRu or PR

    Measured: Up to 2 years

  2. Part 1 Dose Escalation：Compelet response rate (CRR)

    The complete response rate (ORR) is defined as the proportion of patients with a best response of CR or CRu

    Measured: Up to 2 years

  3. Part 1 Dose Escalation：Duration of overall response (DOR)

    The duration of overall response is measured from the time measurement

    Measured: Up to 2 years

  4. Part 1 Dose Escalation：Disease control rate (DCR)

    The disease control rate (DCR) is defined as the proportion of patients with a best response of CR, CRu, PR or SD

    Measured: Up to 2 years

  5. Part 1 Dose Escalation：Progression-free survival (PFS)

    The progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first

    Measured: Up to 2 years

  6. Part 1 Dose Escalation：Overall survival (OS)

    The overall survival (OS) is defined as the duration of time from start of treatment to time of death.

    Measured: Up to 2 years

  7. Part 2 Dose Expansion：Compelet response rate (CRR)

    The complete response rate (ORR) is defined as the proportion of patients with a best response of CR or CRu

    Measured: Up to 2 years

  8. Part 2 Dose Expansion：Duration of overall response (DOR)

    The duration of overall response is measured from the time measurement

    Measured: Up to 2 years

  9. Part 2 Dose Expansion：Disease control rate (DCR)

    The disease control rate (DCR) is defined as the proportion of patients with a best response of CR, CRu, PR or SD

    Measured: Up to 2 years

  10. Part 2 Dose Expansion：Progression-free survival (PFS)

    The progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first

    Measured: Up to 2 years

  11. Part 2 Dose Expansion：Overall survival (OS)

    The overall survival (OS) is defined as the duration of time from start of treatment to time of death.

    Measured: Up to 2 years

  12. The toxicity profile of the orelabrutinib and thiotepa combination therapy

    All subjects who received at least one dose of OT will be included in the safety analysis. Adverse events will be graded by the investigator according to the NCI-CTCAE Version 5.0.

    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.

  1. First posted26 Aug 2021
  2. Study startDec 2021 (estimated)
  3. Primary completionDec 2022 (estimated)
  4. Study completionJun 2024 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
29 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05021770
Sponsor's protocol ID
OT
Status last verified
Aug 2021
First submitted
16 Aug 2021
Last updated
26 Aug 2021
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Orelabrutinib and Thiotepa in people with Refractory and Relapsed Primary CNS Lymphoma and PCNSL, run by Huiqiang Huang 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 19 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 26 Aug 2021. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Huiqiang Huang, Professor (+86 020 87343350, huanghq@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 Dose Escalation：The maximum tolerated dose (MTD) (time frame: Incidence of dose limiting toxicities (DLTs) up to 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05021770.

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 26 Aug 2021; AzTrials last refreshed its copy on 6 Nov 2026.

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