Recurrent/RefractoryPrimary Central Nervous System Lymphoma (PCNSL)Phase 2NCT04129710
A Trial to Compare Ibrutinib Versus Lenalidomide in Combination With MRE-chemotherapy for Adult Patients With Recurrent/Refractory Primary Central Nervous System Lymphoma (PCNSL)
A Phase 2 study testing Ibrutinib, Lenalidomide and Methotrexate in people with Recurrent/RefractoryPrimary Central Nervous System Lymphoma (PCNSL), run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
This is a open-label，multicenter, randomised, three-arm, phase II efficacy and safety study of ibrutinib in combination with MRE(methotrexate,rituximab,etoposide)-chemotherapy versus lenalidomide in combination with MRE-chemotherapy given to adult patients who have recurrent/refractory primary central nervous system… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Recurrent/RefractoryPrimary Central Nervous System Lymphoma (PCNSL)
- What is being tested?
- Ibrutinib, Lenalidomide and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2020to 31 Dec 2025
- 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
- Participants must be able to understand and be willing to sign a written informed consent document.
- Men and woman who are 18-75 years old on the day of consenting to the study.
- Histologically documented PCNSL and histologically documented systemic diffuse large B-cell lymphoma (DLBCL).
- Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL
- All patients need to have received at least one prior CNS directed therapy. There is no restriction on the number of recurrences.
- Patients with parenchymal lesions must have unequivocal evidence of disease progression on imaging (MRI of the brain or head CT) 21 days prior to study registration.
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- Participants must have an ECOG performance status of 0-3.
- Participants must have adequate bone marrow and organ function shown by:
- Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
- Platelets ≥ 75 x 10^9/L and no platelet transfusion within the past 21 days prior to study registration
- Hemoglobin (Hgb) ≥ 8 g/dL and no red blood cell (RBC) transfusion within the past 21 days prior to study registration
- International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper limit of normal
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal
- Serum bilirubin ≤ 1.5 times the upper limit of normal; or total bilirubin ≤ 3 times the upper limit of normal with direct bilirubin within the normal range in patients with well documented Gilbert Syndrome.
- Serum creatinine ≤ 2 times the upper limit of normal
- Woman of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 30 days after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 3 months after the last dose.
- Patients must be able to tolerate MRI/CT scans.
- Participants must have recovered to grade 1 toxicity from prior therapy.
- Participants should be able to submit up to 20 unstained formalin-fixed, paraffinembedded (FFPE) slides from the initial tissue diagnosis prior to study registration for confirmation of diagnosis and correlative studies
- NOTE: Prior autologous stem cell transplant as well as prior radiation to the CNS does NOT prevent patients from enrollment into the trial.
Who cannot join
- Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded.
- Patient has received chemotherapy, monoclonal antibodies or targeted anticancer therapy ≤ 4 weeks or 5 half-lives, whichever is shorter, or 6 weeks for nitrosourea or mitomycin-C prior to starting the study drug, or the patient has not recovered from the side effects of such therapy.
- Patient has received external beam radiation therapy to the CNS within 21 days of the first dose of the study drug.
- Patient requires more than 8 mg of dexamethasone daily or the equivalent
- Patient has an active concurrent malignancy requiring active therapy
- The patient has been treated with radio- or toxin-immunoconjugates within 70 days of the first Patient is allergic to components of the study drug.
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- Patient is using warfarin or any other Coumadin-derivative anticoagulant or vitamin K antagonists. Patients must be off warfarin-derivative anticoagulants for at least seven days prior to starting the study drug. Low molecular weight heparin is allowed. Patients with congenital bleeding diathesis are excluded.
- Patient is taking a drug known to be a moderate and strong inhibitor or inducers of the P450 isoenzyme CYP3A. Participants must be off P450/CYP3A inhibitors and inducers for at least two weeks prior to starting the study drug.
- Patient is using systemic immunosuppressant therapy, including cyclosporine A, tacrolimus, sirolimus, and other such medications, or chronic administration of > 5 mg/day or prednisone or the equivalent. Participants must be off immunosuppressant therapy for at least 28 days prior to the first dose of the study drug.
- Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening,
- Patient has a known bleeding diathesis (e.g. von Willebrand"s disease) or hemophilia.
- Patient is known to have human immunodeficiency virus (HIV) infection.
- Patient is known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests.
- Patient is known to have an uncontrolled active systemic infection.
- Patient underwent major systemic surgery ≤ 4 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.
- Patient is unable to swallow capsules or has a disease or condition significantly affecting gastrointestinal function, such as malabsorption syndrome, resection of the stomach or small bowel, or complete bowel obstruction.
- Patient has a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject"s safety or put the study outcomes at undue risk.
- Women who are pregnant or nursing (lactating), where pregnancy is defined as a state of a female after conception until the termination of gestation, confirmed by a positive serum hCG laboratory test of > 5 mIU/mL (See section on Pregnancy and Reproduction)
- Patient has undergone prior allogenic stem cell transplant (autologous stem cell transplant is NOT an exclusion)
- The patient is unwell or unable to participate in all required study evaluations and procedures
- Known hypersensitivity to ibrutinib, thalidomide or lenalidomide
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, China/Zhejiang Province, 310009
Xiaohong Zhang, MD, +8657189713673, zeyyxy@163.com
About this study
Official title: An Open-label, Multicenter,Randomized Phase 2 Trial to Compare the Efficacy and Safety of Ibrutinib Versus Lenalidomide in Combination With MRE(Methotrexate,Rituximab,Etoposide)-Chemotherapy for Adult Patients With Recurrent/Refractory Primary Central Nervous System Lymphoma (PCNSL)
This is a open-label，multicenter, randomised, three-arm, phase II efficacy and safety study of ibrutinib in combination with MRE(methotrexate,rituximab,etoposide)-chemotherapy versus lenalidomide in combination with MRE-chemotherapy given to adult patients who have recurrent/refractory primary central nervous system lymphoma (PCNSL)
- Being tested
- Ibrutinib, Lenalidomide, Methotrexate, Rituximab, Etoposide
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Ibrutinib 560 mg/day daily (starting dose) between days 4 and 28 of each cycle for six cycles. Then Ibrutinib is continued until disease progression, intolerable toxicity, death or up to two years.
LenalidomideDrug
Oral lenalidomide 25mg/day between days 4 and 24 of each cycle for six cycles. Then lenalidomide is continued until disease progression, intolerable toxicity, death or up to two years.
MethotrexateDrug
Methotrexate 3.5 g/m2 (0.5 g/m2 in 15 min + 3 g/m2 in 3-hr infusion) on day 1
RituximabDrug
Rituximab 375 mg/m2 conventional infusion on day 1
EtoposideDrug
Etoposide 250 mg/m2 over 3 hours on day3
PEGylated recombinant human granulocyte colonyDrug
PEGylated recombinant human granulocyte colony 100 ug/kg subcutaneous injection on day 5.
| Study group | Role | What they receive |
|---|---|---|
| I-MRE | Experimental | Ibrutinib 560 mg/day daily (starting dose) between days 4 and 28 of each cycle for six cycles. Then Ibrutinib is continued until disease progression, intolerable toxicity, death or up to two years.
Methotrexate (standard hydration/leucovorin support) 3.5 g/m2 (0.5 g/m2 in 15 min+ 3 g/m2 in 3-hr infusion) d2.
Rituximab 375 mg/m2 conventional infusion d1.Etoposide 250 mg/m2 over 3 hours on day3.
Every 4 weeks for 1 cycle, 6 cycles will be prescribed as protocol. Receives: Drug: Ibrutinib; Drug: Methotrexate; Drug: Rituximab; Drug: Etoposide; Drug: PEGylated recombinant human granulocyte colony |
| L-MRE | Experimental | Oral lenalidomide 25mg/day (starting dose) between days 4 and 24 of each cycle for six cycles.Then lenalidomide is continued until disease progression, intolerable toxicity, death or up to two years.
Methotrexate (standard hydration/leucovorin support) 3.5 g/m2 (0.5 g/m2 in 15 min+ 3 g/m2 in 3-hr infusion) d2.
Rituximab 375 mg/m2 conventional infusion d1.
Etoposide 250 mg/m2 over 3 hours on day3.
Every 4 weeks for 1 cycle, 6 cycles will be prescribed as protocol. Receives: Drug: Lenalidomide; Drug: Methotrexate; Drug: Rituximab; Drug: Etoposide; Drug: PEGylated recombinant human granulocyte colony |
| MRE | Active comparator | Methotrexate (standard hydration/leucovorin support) 3.5 g/m2 (0.5 g/m2 in 15 min+ 3 g/m2 in 3-hr infusion) d2.
Rituximab 375 mg/m2 conventional infusion d1.
Etoposide 250 mg/m2 over 3 hours on day3.
Every 4 weeks for 1 cycle, 6 cycles will be prescribed as protocol.
Patients who will not achieve SD or better after the 4th course, as well as those who will experience Progressive Disease (PD) at any time will be randomly allocated to the Experimental groups. Receives: Drug: Methotrexate; Drug: Rituximab; Drug: Etoposide; Drug: PEGylated recombinant human granulocyte colony |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
From date of randomization until recurrence/disease progression, unacceptable toxicity, death or discontinuation for any other reason, whichever comes first assessed up to 2 yrs
Measured: assessed up to 2 yrs
Secondary outcomes (3)
Objective response rate (ORR)
To determine efficacy
Measured: assessed up to 2 yrs
Overall survival (OS)
To determine efficacy
Measured: assessed up to 2 yrs
Number of patients with adverse events
Number of participants with treatment- and non-treatment related adverse events as assessed by CTCAE
Measured: assessed up to 2 yrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2019
- Study start1 Jan 2020
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent/RefractoryPrimary Central Nervous System Lymphoma (PCNSL)Studies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Ruijin Hospital, The First Affiliated Hospital of Nanchang University, Fujian Medical University Union Hospital, RenJi Hospital, Shanghai Tong Ren Hospital, Shandong Provincial Hospital, Cancer Hospital of Guangxi Medical University, Sir Run Run Shaw Hospital, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Ningbo Medical Center Lihuili Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Zhejiang University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04129710
- Sponsor's protocol ID
- I2019001413
- Status last verified
- Jan 2021
- First submitted
- 15 Oct 2019
- Last updated
- 16 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: This is a open-label，multicenter, randomised, three-arm, phase II efficacy and safety study of ibrutinib in combination with MRE(methotrexate,rituximab,etoposide)-chemotherapy versus lenalidomide in combination with MRE-chemotherapy given to adult patients who have recurrent/refractory primary central nervous system lymphoma (PCNSL)
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter,Randomized Phase 2 Trial to Compare the Efficacy and Safety of Ibrutinib Versus Lenalidomide in Combination With MRE(Methotrexate,Rituximab,Etoposide)-Chemotherapy for Adult Patients With Recurrent/Refractory Primary Central Nervous System Lymphoma (PCNSL)
- ClinicalTrials.gov ID
- NCT04129710
- Acronym / sponsor ID
- I2019001413
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Ruijin Hospital, The First Affiliated Hospital of Nanchang University, Fujian Medical University Union Hospital, RenJi Hospital, Shanghai Tong Ren Hospital, Shandong Provincial Hospital, Cancer Hospital of Guangxi Medical University, Sir Run Run Shaw Hospital, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Ningbo Medical Center Lihuili Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Zhejiang University
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 17 Oct 2019 (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.
This is a open-label，multicenter, randomised, three-arm, phase II efficacy and safety study of ibrutinib in combination with MRE(methotrexate,rituximab,etoposide)-chemotherapy versus lenalidomide in combination with MRE-chemotherapy given to adult patients who have recurrent/refractory primary central nervous system lymphoma (PCNSL)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| I-MRE | Experimental | Drug: Ibrutinib, Drug: Methotrexate, Drug: Rituximab, Drug: Etoposide, Drug: PEGylated recombinant human granulocyte colonyIbrutinib 560 mg/day daily (starting dose) between days 4 and 28 of each cycle for six cycles. Then Ibrutinib is continued until disease progression, intolerable toxicity, death or up to two years. Methotrexate (standard hydration/leucovorin support) 3.5 g/m2 (0.5 g/m2 in 15 min+ 3 g/m2 in 3-hr infusion) d2. Rituximab 375 mg/m2 conventional infusion d1.Etoposide 250 mg/m2 over 3 hours on day3. Every 4 weeks for 1 cycle, 6 cycles will be prescribed as protocol. |
| L-MRE | Experimental | Drug: Lenalidomide, Drug: Methotrexate, Drug: Rituximab, Drug: Etoposide, Drug: PEGylated recombinant human granulocyte colonyOral lenalidomide 25mg/day (starting dose) between days 4 and 24 of each cycle for six cycles.Then lenalidomide is continued until disease progression, intolerable toxicity, death or up to two years. Methotrexate (standard hydration/leucovorin support) 3.5 g/m2 (0.5 g/m2 in 15 min+ 3 g/m2 in 3-hr infusion) d2. Rituximab 375 mg/m2 conventional infusion d1. Etoposide 250 mg/m2 over 3 hours on day3. Every 4 weeks for 1 cycle, 6 cycles will be prescribed as protocol. |
| MRE | Active comparator | Drug: Methotrexate, Drug: Rituximab, Drug: Etoposide, Drug: PEGylated recombinant human granulocyte colonyMethotrexate (standard hydration/leucovorin support) 3.5 g/m2 (0.5 g/m2 in 15 min+ 3 g/m2 in 3-hr infusion) d2. Rituximab 375 mg/m2 conventional infusion d1. Etoposide 250 mg/m2 over 3 hours on day3. Every 4 weeks for 1 cycle, 6 cycles will be prescribed as protocol. Patients who will not achieve SD or better after the 4th course, as well as those who will experience Progressive Disease (PD) at any time will be randomly allocated to the Experimental groups. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Participants must be able to understand and be willing to sign a written informed consent document.
- Men and woman who are 18-75 years old on the day of consenting to the study.
- Histologically documented PCNSL and histologically documented systemic diffuse large B-cell lymphoma (DLBCL).
- Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL
- All patients need to have received at least one prior CNS directed therapy. There is no restriction on the number of recurrences.
Key exclusion criteria (21 listed)
- Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded.
- Patient has received chemotherapy, monoclonal antibodies or targeted anticancer therapy ≤ 4 weeks or 5 half-lives, whichever is shorter, or 6 weeks for nitrosourea or mitomycin-C prior to starting the study drug, or the patient has not recovered from the side effects of such therapy.
- Patient has received external beam radiation therapy to the CNS within 21 days of the first dose of the study drug.
- Patient requires more than 8 mg of dexamethasone daily or the equivalent
- Patient has an active concurrent malignancy requiring active therapy
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 |
|---|---|---|
| IbrutinibIbrutinib 560 mg/day daily (starting dose) between days 4 and 28 of each cycle for six cycles. Then Ibrutinib is continued until disease progression, intolerable toxicity, death or up to two years. | Drug | I-MRE |
| LenalidomideOral lenalidomide 25mg/day between days 4 and 24 of each cycle for six cycles. Then lenalidomide is continued until disease progression, intolerable toxicity, death or up to two years. | Drug | L-MRE |
| MethotrexateMethotrexate 3.5 g/m2 (0.5 g/m2 in 15 min + 3 g/m2 in 3-hr infusion) on day 1 | Drug | I-MRE, L-MRE, MRE |
| RituximabRituximab 375 mg/m2 conventional infusion on day 1 | Drug | I-MRE, L-MRE, MRE |
| EtoposideEtoposide 250 mg/m2 over 3 hours on day3 | Drug | I-MRE, L-MRE, MRE |
| PEGylated recombinant human granulocyte colonyPEGylated recombinant human granulocyte colony 100 ug/kg subcutaneous injection on day 5. | Drug | I-MRE, L-MRE, MRE |
Primary outcome
Progression-free survival (PFS)
Time frame: assessed up to 2 yrs
From date of randomization until recurrence/disease progression, unacceptable toxicity, death or discontinuation for any other reason, whichever comes first assessed up to 2 yrs
3 secondary outcomes
Objective response rate (ORR)
Time frame: assessed up to 2 yrs
Overall survival (OS)
Time frame: assessed up to 2 yrs
Number of patients with adverse events
Time frame: assessed up to 2 yrs
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2021.
- Individual participant dataSharing planned: Yes. This is a open-label，multicenter, randomised, three-arm, phase II efficacy and safety study of ibrutinib in combination with MRE(methotrexate,rituximab,etoposide)-chemotherapy versus lenalidomide in combination with MRE-chemotherapy given to adult patients who have recurrent/refractory primary central nervous system lymphoma (PCNSL)
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib, Lenalidomide and Methotrexate in people with Recurrent/RefractoryPrimary Central Nervous System Lymphoma (PCNSL), run by Second Affiliated Hospital, Zhejiang University, School of Medicine 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 20 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 16 Jul 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 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 Xiaohong Zhang (+8657189713673, zeyyxy@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) (time frame: assessed up to 2 yrs). 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 16 Jul 2021.