High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 RearrangementsPhase 3NCT05097443
Orelabrutinib, Rituximab and Combination Chemotherapy in Newly-diagnosed Aggressive B-cell Non-Hodgkin Lymphoma
A Phase 3 study testing Orelabrutinib+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapies in people with High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements and High Grade B-Cell Lymphoma, Not Otherwise Specified, run by Shandong Provincial Hospital at 1 site in China.
Trial summary
B-cell non-Hodgkin's lymphoma (B-NHL) is the most common type of NHL. Although novel immunotherapies represented by anti-CD20 monoclonal antibodies and CAR-T cell therapies have significantly improved the prognosis of B-NHL patients, there are still nearly one-third of patients who are resistant to initial treatment… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Diffuse Large B-cell Lymphoma
- What is being tested?
- Orelabrutinib+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapies
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteChina
- Study dates
- 15 Apr 2021to 31 Dec 2024
- Phase
- Phase 3
- 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
- Age ≥18 years, gender not limited
- Newly and histologically diagnosed aggressive B-NHL
- Patients who have not received systematic chemotherapy or immunotherapy;
- Patients with at least ≥1 tumor foci with a measurable maximum axis exceeding 1.5 cm;
- Eastern cancer collaboration group(ECOG) physical status score: 0-2
- Major organ functions meet the following criteria:
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- Blood routine: (independent of growth factor support or transfusion within 7 days of study entry) neutrophils absolute value ≥1.5×109/L, platelets ≥75×109/L,
- Coagulation function：INR and APTT ≤2.5 times ULN，
- Blood biochemistry：total bilirubin ≤2 times ULN, AST or ALT≤2.5 times ULN;
- Renal function: Ccr ≥ 50 mL/min, total bilirubin, AST or ALT≤2.5 times ULN
- Willing to take contraceptive measures during the trial period and within 3 months after the trial ends；
- Voluntarily sign written informed consent before screening.
Who cannot join
- Current or previous malignancy, unless radical therapy has been performed and there is no evidence of recurrence or metastasis in the past 5 years；
- Patients scheduled for major surgery(examination for diagnostic purposes) within 4 weeks or participating in drug/device clinical trials;
- Prior or concurrent indolent B-cell lymphoma transformation;
- Have uncontrolled or significant cardiovascular disease, including:
- New York Heart Association (NYHA) Grade II or higher congestive heart failure, unstable angina, and myocardial infarction occurred within 6 months before the first administration of the study drug or arrhythmia needing treatment at the time of screening, LVEF <50%；
- Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy)；
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- Clinically significant QTc interval prolongation history, or QTc interval >470ms for female and >450ms for male in the screening period；
- Symptomatic coronary heart disease patients or needing treatment;
- Uncontrolled high blood pressure (on the basis of improving lifestyle, substandard blood pressure with reasonable and tolerable application of 2 or more antihypertensive drugs including diuretics for more than 1 month, or taking 4 or more antihypertensive drugs to control blood pressure effectively)；
- 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;
- Stroke or intracranial hemorrhage within 6 months；
- Subjects with clinically significant gastrointestinal abnormalities that may affect drug intake, transport or absorption (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
- Active or uncontrolled HBV (HBsAg positive and HBV DNA titer positive), HCV Ab positive or HIV positive；
- Uncontrolled, active systemic fungal, bacterial, viral, or other infections (defined as showing persistent signs/symptoms related to infection, despite the use of appropriate antibiotics or other treatments without improvement)；
- Allergies or hypersensitivity reactions to orelabrutinib, rituximab or any other component of the applicable study drug;
- Combined with drugs with moderate to severe inhibitory effect or strong induction effect on CYP3A;
- Severe mental illness;
- Expected survival <6 months
- Pregnant and lactating women; For women of childbearing age who do not agree to use appropriate methods of contraception;
- Poor compliance or inability to visit regularly;
- Potentially life-threatening patients, or severe organ dysfunction, judged unsuitable for this trail by investigators.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shandong Provincial Hospital
Jinan, Shandong, 250021
Xin Wang, PhD, +86-531-13156012606, xinw@sdu.edu.cn
Xiangxiang Zhou, PhD, +86-531-15866695595, xiangxiangzhou@sdu.edu.cn
About this study
Official title: A Multi-center and Prospective Clinical Study of Orelabrutinib, Rituximab and Combination Chemotherapy in Patients With Newly-diagnosed Aggressive B-cell Non-Hodgkin Lymphoma
B-cell non-Hodgkin's lymphoma (B-NHL) is the most common type of NHL. Although novel immunotherapies represented by anti-CD20 monoclonal antibodies and CAR-T cell therapies have significantly improved the prognosis of B-NHL patients, there are still nearly one-third of patients who are resistant to initial treatment or relapse after remission. R-CHOP combined with novel drugs was expected to improve the prognosis. Therefore, this study aimed to investigate the potential of Orelabrutinib combined with Rituximab and chemotherapy.
Read the detailed description
Non-Hodgkin lymphoma (NHL), with high aggressiveness and mortality, is one of the top ten high-incidence tumors in the world and is among the ten most prevalent cancers worldwide with the fastest growing incidence. B-cell non-Hodgkin's lymphoma (B-NHL) is the most common type of NHL. Although novel immunotherapies represented by anti-CD20 monoclonal antibodies and CAR-T cell therapies have significantly improved the prognosis of B-NHL patients, there are still nearly one-third of patients who are resistant to initial treatment or relapse after remission. In recent years, the continuous emergence of various novel targeted agents has provided new hope for the treatment of B-NHL.
Brutons tyrosine kinase (BTK) is a vital protein for immune B cell function, and a core switch of B cell growth, controlling cellular proliferation, differentiation, apoptosis and migration. BTK inhibitors were available as a breakthrough therapy at the end of 2013, providing a possibility of cure in patients with B-NHL. Orelabrutinib is a highly selective novel BTK inhibitor, and its latest clinical data was announced at the 62nd Annual Meeting of the American Society of Hematology (ASH) on Dec 7, 2020. In two clinical studies targeting relapsed/refractory mantle cell lymphoma (MCL) and relapsed/refractory chronic lymphocytic leukemia (CLL)/small cell leukemia (SLL), orelabrutinib showed a favorable overall remission rate (ORR) and safety. In a phase II clinical study on the treatment of relapsed/refractory CLL/SLL, at a median follow-up of 14.3 months, ORR was 91.3%. The median time to response was 1.87 months, and the median PFS or DOR was not reached. In a phase II clinical study on the treatment of relapsed/refractory MCL, at a median follow-up of 16.4 months, ORR was 87.9%. 93.9% of patients achieved disease control. However, the efficacy of orelabrutinib in highly aggressive B-cell lymphoma remains to be further studied.
Therefore, we present this study protocol to add orelabrutinib to the first-line treatment of highly aggressive B-NHL, applying orelabrutinib+R-CHOP/R-EPOCH/R-HD-MTX/R-other regimens, to clarify the efficacy of orelabrutinib+R-CHOP/R-EPOCH/R-HD-MTX/R-other regimens and explore a set of potent and safe treatments for B-NHL patients with high risks and further improve the prognosis.
- Conditions
- High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, B-cell NonHodgkin Lymphoma
- Being tested
- Orelabrutinib+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapies
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Orelabrutinib+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapiesDrug
Orelabrutinib+R-CHOP： Orelabrutinib 150mg qd; R-CHOP：Rituximab 375mg/m2 d0, Cyclophosphamide 750mg /m2 d1, Doxorubicin 50mg /m2 or Doxorubicin liposome 30-40 mg /m2 d1, Vincristine 1.4mg /m2 or Vindesine 3mg /m2 d1, Prednisone 100mg d1-5.
Orelabrutinib+R-DA-EPOCH： Orelabrutinib 150mg qd； R-DA-EPOCH：Rituximab 375mg/m2 d0, Etoposide 50mg/ m2, Epirubicin 15mg/ m2, Vincristine 0.4mg/ m2, d1-4, Cyclophosphamide 750mg/ m2 d5, Prednisone 60mg/ m2 d1-5.
Orelabrutinib+R-HD-MTX: Orelabrutinib 150mg qd; R-HD-MTX: Rituximab 375mg/m2 d0, Methotrexate 3.5g/ｍ2 d1.
Orelabrutinib+ R+other regimens: Orelabrutinib 150mg qd； R+other regimens: Rituximab 375mg/m2 d0. The dose of other drugs depends on the regimen.
All regimens follow every 21 days is one cycle, which can be extended to 28 days per cycle according to patients' specific tolerance.
Dose adjustments of Orelabrutinib are allowed. The initial dose is 150 mg, QD, while the first adjustment is 100 mg, QD and the second adjustment is 50 mg, QD.
| Study group | Role | What they receive |
|---|---|---|
| Orelabrutinib+R+chemotherapy | Experimental | Orelabrutinib+R-CHOP;Orelabrutinib+R-DA-EPOCH;Orelabrutinib+R-HD MTX；Orelabrutinib+R+other regimens Receives: Drug: Orelabrutinib+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapies |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
Measured: At the end of Cycle 6 (each cycle is 21 days)
Secondary outcomes (3)
Occurrence of adverse events and serious adverse events
per cycle
Measured: 3 years
progression-free survival (PFS)
Measured: 3 years
Overall survival (OS)
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2021
- Study start15 Apr 2021
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 RearrangementsStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong Provincial Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Wang Xin, Shandong Provincial Hospital
- Investigators
- Xin Wang, PhD, Principal investigator, Shandong Provincial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05097443
- Sponsor's protocol ID
- B-NHL001
- Status last verified
- Nov 2021
- First submitted
- 26 Oct 2021
- Last updated
- 19 Nov 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center and Prospective Clinical Study of Orelabrutinib, Rituximab and Combination Chemotherapy in Patients With Newly-diagnosed Aggressive B-cell Non-Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT05097443
- Acronym / sponsor ID
- B-NHL001
- Conditions
- High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, High Grade B-Cell Lymphoma, Not Otherwise Specified, Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, B-cell NonHodgkin Lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Shandong Provincial HospitalOther government
- Study start
- 15 Apr 2021 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 28 Oct 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.
B-cell non-Hodgkin's lymphoma (B-NHL) is the most common type of NHL. Although novel immunotherapies represented by anti-CD20 monoclonal antibodies and CAR-T cell therapies have significantly improved the prognosis of B-NHL patients, there are still nearly one-third of patients who are resistant to initial treatment or relapse after remission. R-CHOP combined with novel drugs was expected to improve the prognosis. Therefore, this study aimed to investigate the potential of Orelabrutinib combined with Rituximab and chemotherapy.
Detailed description
Non-Hodgkin lymphoma (NHL), with high aggressiveness and mortality, is one of the top ten high-incidence tumors in the world and is among the ten most prevalent cancers worldwide with the fastest growing incidence. B-cell non-Hodgkin's lymphoma (B-NHL) is the most common type of NHL. Although novel immunotherapies represented by anti-CD20 monoclonal antibodies and CAR-T cell therapies have significantly improved the prognosis of B-NHL patients, there are still nearly one-third of patients who are resistant to initial treatment or relapse after remission. In recent years, the continuous emergence of various novel targeted agents has provided new hope for the treatment of B-NHL.
Brutons tyrosine kinase (BTK) is a vital protein for immune B cell function, and a core switch of B cell growth, controlling cellular proliferation, differentiation, apoptosis and migration. BTK inhibitors were available as a breakthrough therapy at the end of 2013, providing a possibility of cure in patients with B-NHL. Orelabrutinib is a highly selective novel BTK inhibitor, and its latest clinical data was announced at the 62nd Annual Meeting of the American Society of Hematology (ASH) on Dec 7, 2020. In two clinical studies targeting relapsed/refractory mantle cell lymphoma (MCL) and relapsed/refractory chronic lymphocytic leukemia (CLL)/small cell leukemia (SLL), orelabrutinib showed a favorable overall remission rate (ORR) and safety. In a phase II clinical study on the treatment of relapsed/refractory CLL/SLL, at a median follow-up of 14.3 months, ORR was 91.3%. The median time to response was 1.87 months, and the median PFS or DOR was not reached. In a phase II clinical study on the treatment of relapsed/refractory MCL, at a median follow-up of 16.4 months, ORR was 87.9%. 93.9% of patients achieved disease control. However, the efficacy of orelabrutinib in highly aggressive B-cell lymphoma remains to be further studied.
Therefore, we present this study protocol to add orelabrutinib to the first-line treatment of highly aggressive B-NHL, applying orelabrutinib+R-CHOP/R-EPOCH/R-HD-MTX/R-other regimens, to clarify the efficacy of orelabrutinib+R-CHOP/R-EPOCH/R-HD-MTX/R-other regimens and explore a set of potent and safe treatments for B-NHL patients with high risks and further improve the prognosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Orelabrutinib+R+chemotherapy | Experimental | Drug: Orelabrutinib+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapiesOrelabrutinib+R-CHOP;Orelabrutinib+R-DA-EPOCH;Orelabrutinib+R-HD MTX；Orelabrutinib+R+other regimens |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥18 years, gender not limited
- Newly and histologically diagnosed aggressive B-NHL
- Patients who have not received systematic chemotherapy or immunotherapy;
- Patients with at least ≥1 tumor foci with a measurable maximum axis exceeding 1.5 cm;
- Eastern cancer collaboration group(ECOG) physical status score: 0-2
Key exclusion criteria (21 listed)
- Current or previous malignancy, unless radical therapy has been performed and there is no evidence of recurrence or metastasis in the past 5 years；
- Patients scheduled for major surgery(examination for diagnostic purposes) within 4 weeks or participating in drug/device clinical trials;
- Prior or concurrent indolent B-cell lymphoma transformation;
- Have uncontrolled or significant cardiovascular disease, including:
- 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;
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+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapiesOrelabrutinib+R-CHOP： Orelabrutinib 150mg qd; R-CHOP：Rituximab 375mg/m2 d0, Cyclophosphamide 750mg /m2 d1, Doxorubicin 50mg /m2 or Doxorubicin liposome 30-40 mg /m2 d1, Vincristine 1.4mg /m2 or Vindesine 3mg /m2 d1, Prednisone 100mg d1-5. Orelabrutinib+R-DA-EPOCH： Orelabrutinib 150mg qd； R-DA-EPOCH：Rituximab 375mg/m2 d0, Etoposide 50mg/ m2, Epirubicin 15mg/ m2, Vincristine 0.4mg/ m2, d1-4, Cyclophosphamide 750mg/ m2 d5, Prednisone 60mg/ m2 d1-5. Orelabrutinib+R-HD-MTX: Orelabrutinib 150mg qd; R-HD-MTX: Rituximab 375mg/m2 d0, Methotrexate 3.5g/ｍ2 d1. Orelabrutinib+ R+other regimens: Orelabrutinib 150mg qd； R+other regimens: Rituximab 375mg/m2 d0. The dose of other drugs depends on the regimen. All regimens follow every 21 days is one cycle, which can be extended to 28 days per cycle according to patients' specific tolerance. Dose adjustments of Orelabrutinib are allowed. The initial dose is 150 mg, QD, while the first adjustment is 100 mg, QD and the second adjustment is 50 mg, QD. | Drug | Orelabrutinib+R+chemotherapy |
Primary outcome
ORR
Time frame: At the end of Cycle 6 (each cycle is 21 days)
3 secondary outcomes
Occurrence of adverse events and serious adverse events
Time frame: 3 years
progression-free survival (PFS)
Time frame: 3 years
Overall survival (OS)
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2021.
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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.
Xin Wang, PhD principal investigator
Shandong Provincial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Orelabrutinib+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapies in people with High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements and High Grade B-Cell Lymphoma, Not Otherwise Specified, run by Shandong Provincial Hospital 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 12 inclusion and 21 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 19 Nov 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Xin Wang, PhD (86-531-13156012606, xinw@sdu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: At the end of Cycle 6 (each cycle is 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Nov 2021.