A Trial to Compare Ibrutinib Versus Lenalidomide in Combination With MRE-chemotherapy for Adult Patients With Recurrent/Refractory Primary Central Nervous System Lymphoma (PCNSL)

NCT04129710 | Unknown Phase 2

• 1 other identifier: I2019001413
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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 lymphoma (PCNSL)

Conditions

Recurrent/RefractoryPrimary Central Nervous System Lymphoma (PCNSL)

Outcome Measures

Primary Outcomes (1)

• 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

  assessed up to 2 yrs

Secondary Outcomes (3)

• Objective response rate (ORR)

  assessed up to 2 yrs

• Overall survival (OS)

  assessed up to 2 yrs

• Number of patients with adverse events

  assessed up to 2 yrs

Study Arms (3)

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.

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.

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.

Drug: Methotrexate; Drug: Rituximab; Drug: Etoposide; Drug: PEGylated recombinant human granulocyte colony

Interventions

Ibrutinib DRUG

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.

I-MRE

Lenalidomide DRUG

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.

L-MRE

Methotrexate DRUG

Methotrexate 3.5 g/m2 (0.5 g/m2 in 15 min + 3 g/m2 in 3-hr infusion) on day 1

I-MRE; L-MRE; MRE

Rituximab DRUG

Rituximab 375 mg/m2 conventional infusion on day 1

I-MRE; L-MRE; MRE

Etoposide DRUG

Etoposide 250 mg/m2 over 3 hours on day3

I-MRE; L-MRE; MRE

PEGylated recombinant human granulocyte colony DRUG

PEGylated recombinant human granulocyte colony 100 ug/kg subcutaneous injection on day 5.

I-MRE; L-MRE; MRE

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Ruijin Hospital: collaborator
• The First Affiliated Hospital of Nanchang University: collaborator
• Fujian Medical University Union Hospital: collaborator
• RenJi Hospital: collaborator
• Shanghai Tong Ren Hospital: collaborator
• Shandong Provincial Hospital: collaborator
• Cancer Hospital of Guangxi Medical University: collaborator
• Sir Run Run Shaw Hospital: collaborator
• Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University: collaborator
• Ningbo Medical Center Lihuili Hospital: collaborator
• Yinzhou Hospital Affiliated to Medical School of Ningbo University: collaborator
• Zhejiang University: collaborator

Study Sites (1)

Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, China/Zhejiang Province, 310009, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

ibrutinib; Lenalidomide; Methotrexate; Rituximab; Etoposide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Central Study Contacts

Xiaohong Zhang

CONTACT

+8657189713673; zeyyxy@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 17, 2019
• Study Start: January 1, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2025
• Last Updated: July 16, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

CN (1)