B-cell LymphomaPhase 2NCT05014100
Orelabrutinib in Combination With R2 Regimen for R/R CD20+ B-cell Lymphoma
A Phase 2 study testing Orelabrutinib tablet and Lenalidomide in people with B-cell Lymphoma, run by Puyang Oilfield General Hospital.
Trial summary
Obrutinib is a highly selective BTKi and has shown efficacy in CLL/MCL. This study aims to investigate the initial efficacy and safety of obrutinib combined with R2 regimen in the treatment of relapsed or refractory CD20+B cell lymphoma Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- B-cell Lymphoma
- What is being tested?
- Orelabrutinib tablet and Lenalidomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2021to 30 Sep 2023
- Phase
- Phase 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1) Age ≥18 years old, ≤75 years old, gender is not limited;
- 2) CD20+B cell lymphoma was confirmed by histopathology, with at least one intranode lesion larger than 1.5CM in length and extranodal lesion larger than 1.0CM in diameter.
- 3) Patients with recurrent or refractory CD20+ B-cell lymphoma who have previously received ≥1 line and ≤5 line of different chemotherapy and/or targeted drug therapy failure and lack effective and standard treatment options;
- 4) ECOG strength score 0-2;
- 5) Medical records that have failed to respond to the latest systematic treatment (not reaching CR/PR) or disease progression after remission;
- 6) Major organ functions meet the following criteria:
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- Blood routine: neutrophils absolute value ≥1.5×109/L, platelets ≥75×109/L, hemoglobin ≥75g/L; Absolute neutrophils if associated with bone marrow invasion
- ≥1.0×109/L, platelet ≥50×109/L, hemoglobin ≥75g/L;
- Blood biochemistry: total bilirubin ≤1.5 times ULN, AST or ALT≤3 times ULN; Serum creatinine ≤1.5 ULN; Serum amylase ≤ULN;
- Coagulation function: International standardized ratio (INR) ≤1.5 times ULN.
- 7) Expected survival ≥3 months;
- 8) Voluntarily sign written informed consent before screening.
Who cannot join
- 1) Current or previous malignancy, unless radical therapy has been performed and there is no evidence of recurrence or metastasis in the past 5 years;
- 2) Non-hematologic toxicity of previous antitumor therapy did not return to ≤ grade 1 (excluding hair loss)
- 3) Have uncontrolled or significant cardiovascular disease
- 7) Had active bleeding within 2 months prior to screening, or was taking anticoagulant drugs, or was considered by the investigator to have a clear tendency to bleeding;
- Urine protein ≥2+, and 24 h urine protein quantification ≥ 2G /24 h;
- 9) History of deep vein thrombosis or pulmonary embolism;
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- 10) The toxicity of the pre-screening treatment regimen has not recovered, and there are still toxicity reactions above grade 1;
- 11) Subjects with clinically significant gastrointestinal abnormalities that may affect drug intake, transport or absorption (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or total gastrectomy;
- 12) A history of organ transplantation or allogeneic bone marrow transplantation;
- 13) Major surgery or minor surgery within 6 weeks prior to screening or 2 weeks prior to screening. Major surgery is surgery performed under general anesthesia, but endoscopic examination for diagnostic purposes is not considered major surgery. Insertion of vascular access devices will be exempt from this exclusion criterion;
- 14) Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C virus infection (positive results by POLYMERase chain reaction [PCR]).
- 15) Current subjects with pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of lung function;
- 16) Suitable and ready for stem cell transplantation;
- 17) Any mental or cognitive impairment that may limit his/her understanding, implementation and compliance with the informed consent;
- 18) Subjects with drug and alcohol abuse;
- 19) Pregnant and lactating women and subjects of childbearing age who do not want to take contraceptive measures;
- 20) Combined with drugs with moderate to severe inhibitory effect or strong induction effect on cytochrome P450 CYP3A;
- 21) Other conditions that the researcher considers unsuitable to participate in this study.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Multicenter Clinical Study of Orelabrutinib Combined With Lenalidomide and Rituximab (OR2) in the Treatment of Recurrent and Refractory CD20+ B-cell Lymphoma
Obrutinib is a highly selective BTKi and has shown efficacy in CLL/MCL. This study aims to investigate the initial efficacy and safety of obrutinib combined with R2 regimen in the treatment of relapsed or refractory CD20+B cell lymphoma
Read the detailed description
Bruton's tyrosine kinase (BTK), a member of the TEC family of non-receptor tyrosine proteins, is expressed in B lymphocytes, mast cells, macrophages, monocytes, neutrophils, etc., and is a key molecule in the signaling of B cell antigen receptor (BCR). The development and differentiation of B cells can be controlled by activating positive cell cycle regulators and differentiated cytokines, and the survival and proliferation of B cells can be controlled by regulating the expression of pro-apoptotic and anti-apoptotic proteins. BTK inhibitors inhibit B cell maturation and activation by targeting the BCR signaling pathway.
Compared with other BTK inhibitors, orelabrutinib is highly selective. Previous studies showed that among 456 tested kinases, the inhibition rate of orelabrutinib only exceeded 90% at 1µM concentration, which is the BTK inhibitor with the highest kinase selectivity reported so far. It has shown a good safe treatment window in animal models, and its pharmacokinetic properties are far superior to those of ibrutinib.
In the Phase I dose exploration study of orelabrutinib in Australia, the single dose was from 20mg/ day to 400mg/ day, and the continuous dose was from 100mg/ day to 200mg/ day. No serious adverse events related to the drug occurred, and no dosion-limiting toxicity was found. The main adverse reactions were headache, intubation pain, fatigue, etc. Most of them were mild and generally well tolerated, providing a reference for the selection of subsequent clinical drug dosage.
Phase I/II clinical trials of orelabrutinib for MCL and CLL/SLL have been conducted in more than 20 centers across the country. Based on preliminary results observed in Phase I, obrutinib has demonstrated excellent safety and tolerability in patients with relapsed refractory MCL and CLL/SLL. Most of the adverse reactions were grade 1-2. Good results have been observed early on in patients. Good pharmacokinetic/pharmacokinetic properties.
Several studies have shown that ibrutinib combined with lenalidomide and rituximab improves survival in patients with relapsed refractory diffuse large B-cell lymphoma. In addition, ibrutinib combined with lenalidomide and rituximab has been included in the expert recommendation of multiple relapsed and refractory B-cell lymphomas in the 2021CSCO Lymphoma Guidelines.
In conclusion, orelabrutinib and lenalidomide combined with rituximab demonstrated good efficacy and tolerability in the treatment of relapsed refractory B-cell lymphoma. Moreover,orelabrutinib has better selectivity than ibrutinib, so we believe that orelabrutinib combined with lenalidomide and rituximab (OR2) may have better efficacy in the treatment of relapsed and refractory B-cell lymphoma, and there is no research report on this regimen. The application of this regimen may bring new hope for relapsed refractory B-cell lymphoma.
- Conditions
- B-cell Lymphoma
- Being tested
- Orelabrutinib tablet, Lenalidomide
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Orelabrutinib tabletDrug
Subjects received orelabrutinib150mg orally once daily for a 28-day cycle. Throughout the study period, all subjects continued treatment until one of the following conditions occurred: disease progression, intolerable toxicity, death, withdrawal of informed consent, or loss of follow-up
LenalidomideDrug
Also called RR
Lenalidomide 25mg once daily for 21 days and rituximab 375mg/m2 for 7 days
Throughout the study period, all subjects continued treatment until one of the following conditions occurred: disease progression, intolerable toxicity, death, withdrawal of informed consent, or loss of follow-up
| Study group | Role | What they receive |
|---|---|---|
| The treatment group | Experimental | Orelabrutinib 150mg once daily in a 28-day cycle. Lenalidomide 25mg once daily for 21 days and rituximab 375mg/m2 for 7 days Receives: Drug: Orelabrutinib tablet; Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate
The proportion of patients receiving a OR2 regimens who are in remission
Measured: Enrollment to the last patient complete 6cycles（each cycle is 28 days）, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2021
- Study start1 Sep 2021 (estimated)
- Primary completion30 Sep 2022 (estimated)
- Study completion30 Sep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for B-cell LymphomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Puyang Oilfield General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xuejun Guo, PHD, Principal investigator, Puyang Oilfield General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05014100
- Sponsor's protocol ID
- PYOFGHhema001
- Status last verified
- Jul 2021
- First submitted
- 29 Jul 2021
- Last updated
- 27 Aug 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ujjani C, Wang H, Skarbnik A, Trivedi N, Ramzi P, Khan N, Cheson BD. A phase 1 study of lenalidomide and ibrutinib in combination with rituximab in relapsed and refractory CLL. Blood Adv. 2018 Apr 10;2(7):762-768. doi: 10.1182/bloodadvances.2017015263.
PubMed 29610115Ujjani CS, Jung SH, Pitcher B, Martin P, Park SI, Blum KA, Smith SM, Czuczman M, Davids MS, Levine E, Lewis LD, Smith SE, Bartlett NL, Leonard JP, Cheson BD. Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103. Blood. 2016 Nov 24;128(21):2510-2516. doi: 10.1182/blood-2016-06-718106. Epub 2016 Oct 3.
PubMed 27697771Goy A, Ramchandren R, Ghosh N, Munoz J, Morgan DS, Dang NH, Knapp M, Delioukina M, Kingsley E, Ping J, Beaupre DM, Neuenburg JK, Ruan J. Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed/refractory non-germinal center B-cell-like DLBCL. Blood. 2019 Sep 26;134(13):1024-1036. doi: 10.1182/blood.2018891598. Epub 2019 Jul 22.
PubMed 31331917Yu H, Wang X, Li J, Ye Y, Wang D, Fang W, Mi L, Ding N, Wang X, Song Y, Zhu J. Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma. Mol Ther Oncolytics. 2021 Apr 3;21:158-170. doi: 10.1016/j.omto.2021.03.015. eCollection 2021 Jun 25.
PubMed 33981831
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Clinical Study of Orelabrutinib Combined With Lenalidomide and Rituximab (OR2) in the Treatment of Recurrent and Refractory CD20+ B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT05014100
- Acronym / sponsor ID
- PYOFGHhema001
- Conditions
- B-cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Puyang Oilfield General HospitalUniversity, hospital or other
- Study start
- 1 Sep 2021 (estimated)
- Primary completion
- 30 Sep 2022 (estimated)
- Study completion
- 30 Sep 2023 (estimated)
- First posted
- 20 Aug 2021 (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.
Obrutinib is a highly selective BTKi and has shown efficacy in CLL/MCL. This study aims to investigate the initial efficacy and safety of obrutinib combined with R2 regimen in the treatment of relapsed or refractory CD20+B cell lymphoma
Detailed description
Bruton's tyrosine kinase (BTK), a member of the TEC family of non-receptor tyrosine proteins, is expressed in B lymphocytes, mast cells, macrophages, monocytes, neutrophils, etc., and is a key molecule in the signaling of B cell antigen receptor (BCR). The development and differentiation of B cells can be controlled by activating positive cell cycle regulators and differentiated cytokines, and the survival and proliferation of B cells can be controlled by regulating the expression of pro-apoptotic and anti-apoptotic proteins. BTK inhibitors inhibit B cell maturation and activation by targeting the BCR signaling pathway.
Compared with other BTK inhibitors, orelabrutinib is highly selective. Previous studies showed that among 456 tested kinases, the inhibition rate of orelabrutinib only exceeded 90% at 1µM concentration, which is the BTK inhibitor with the highest kinase selectivity reported so far. It has shown a good safe treatment window in animal models, and its pharmacokinetic properties are far superior to those of ibrutinib.
In the Phase I dose exploration study of orelabrutinib in Australia, the single dose was from 20mg/ day to 400mg/ day, and the continuous dose was from 100mg/ day to 200mg/ day. No serious adverse events related to the drug occurred, and no dosion-limiting toxicity was found. The main adverse reactions were headache, intubation pain, fatigue, etc. Most of them were mild and generally well tolerated, providing a reference for the selection of subsequent clinical drug dosage.
Phase I/II clinical trials of orelabrutinib for MCL and CLL/SLL have been conducted in more than 20 centers across the country. Based on preliminary results observed in Phase I, obrutinib has demonstrated excellent safety and tolerability in patients with relapsed refractory MCL and CLL/SLL. Most of the adverse reactions were grade 1-2. Good results have been observed early on in patients. Good pharmacokinetic/pharmacokinetic properties.
Several studies have shown that ibrutinib combined with lenalidomide and rituximab improves survival in patients with relapsed refractory diffuse large B-cell lymphoma. In addition, ibrutinib combined with lenalidomide and rituximab has been included in the expert recommendation of multiple relapsed and refractory B-cell lymphomas in the 2021CSCO Lymphoma Guidelines.
In conclusion, orelabrutinib and lenalidomide combined with rituximab demonstrated good efficacy and tolerability in the treatment of relapsed refractory B-cell lymphoma. Moreover,orelabrutinib has better selectivity than ibrutinib, so we believe that orelabrutinib combined with lenalidomide and rituximab (OR2) may have better efficacy in the treatment of relapsed and refractory B-cell lymphoma, and there is no research report on this regimen. The application of this regimen may bring new hope for relapsed refractory B-cell lymphoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| The treatment group | Experimental | Drug: Orelabrutinib tablet, Drug: LenalidomideOrelabrutinib 150mg once daily in a 28-day cycle. Lenalidomide 25mg once daily for 21 days and rituximab 375mg/m2 for 7 days |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 1) Age ≥18 years old, ≤75 years old, gender is not limited;
- 2) CD20+B cell lymphoma was confirmed by histopathology, with at least one intranode lesion larger than 1.5CM in length and extranodal lesion larger than 1.0CM in diameter.
- 3) Patients with recurrent or refractory CD20+ B-cell lymphoma who have previously received ≥1 line and ≤5 line of different chemotherapy and/or targeted drug therapy failure and lack effective and standard treatment options;
- 4) ECOG strength score 0-2;
- 5) Medical records that have failed to respond to the latest systematic treatment (not reaching CR/PR) or disease progression after remission;
Key exclusion criteria (18 listed)
- 1) Current or previous malignancy, unless radical therapy has been performed and there is no evidence of recurrence or metastasis in the past 5 years;
- 2) Non-hematologic toxicity of previous antitumor therapy did not return to ≤ grade 1 (excluding hair loss)
- 3) Have uncontrolled or significant cardiovascular disease
- 7) Had active bleeding within 2 months prior to screening, or was taking anticoagulant drugs, or was considered by the investigator to have a clear tendency to bleeding;
- 9) History of deep vein thrombosis or pulmonary embolism;
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 |
|---|---|---|
| Orelabrutinib tabletSubjects received orelabrutinib150mg orally once daily for a 28-day cycle. Throughout the study period, all subjects continued treatment until one of the following conditions occurred: disease progression, intolerable toxicity, death, withdrawal of informed consent, or loss of follow-up | Drug | The treatment group |
| LenalidomideAlso: RRLenalidomide 25mg once daily for 21 days and rituximab 375mg/m2 for 7 days Throughout the study period, all subjects continued treatment until one of the following conditions occurred: disease progression, intolerable toxicity, death, withdrawal of informed consent, or loss of follow-up | Drug | The treatment group |
Primary outcome
Complete response rate
Time frame: Enrollment to the last patient complete 6cycles（each cycle is 28 days）, an average of 1 year
The proportion of patients receiving a OR2 regimens who are in remission
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2021.
- Background: PubMed 29610115Ujjani C, Wang H, Skarbnik A, Trivedi N, Ramzi P, Khan N, Cheson BD. A phase 1 study of lenalidomide and ibrutinib in combination with rituximab in relapsed and refractory CLL. Blood Adv. 2018 Apr 10;2(7):762-768. doi: 10.1182/bloodadvances.2017015263.
- Background: PubMed 27697771Ujjani CS, Jung SH, Pitcher B, Martin P, Park SI, Blum KA, Smith SM, Czuczman M, Davids MS, Levine E, Lewis LD, Smith SE, Bartlett NL, Leonard JP, Cheson BD. Phase 1 trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103. Blood. 2016 Nov 24;128(21):2510-2516. doi: 10.1182/blood-2016-06-718106. Epub 2016 Oct 3.
- Background: PubMed 31331917Goy A, Ramchandren R, Ghosh N, Munoz J, Morgan DS, Dang NH, Knapp M, Delioukina M, Kingsley E, Ping J, Beaupre DM, Neuenburg JK, Ruan J. Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed/refractory non-germinal center B-cell-like DLBCL. Blood. 2019 Sep 26;134(13):1024-1036. doi: 10.1182/blood.2018891598. Epub 2019 Jul 22.
- Background: PubMed 33981831Yu H, Wang X, Li J, Ye Y, Wang D, Fang W, Mi L, Ding N, Wang X, Song Y, Zhu J. Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma. Mol Ther Oncolytics. 2021 Apr 3;21:158-170. doi: 10.1016/j.omto.2021.03.015. eCollection 2021 Jun 25.
- 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.
Xuejun Guo, PHD principal investigator
Puyang Oilfield General Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Orelabrutinib tablet and Lenalidomide in people with B-cell Lymphoma, run by Puyang Oilfield General Hospital.
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 12 inclusion and 18 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 27 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
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 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 Xuejun Guo, PHD (+86 13903930612, pygxj@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response rate (time frame: Enrollment to the last patient complete 6cycles（each cycle is 28 days）, an average of 1 year). 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 NCT05014100, which also lists 4 linked publications.
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 27 Aug 2021; AzTrials last refreshed its copy on 6 Nov 2026.