Clinical Trials /

A Study of Ibrutinib With Rituximab in People With Untreated Marginal Zone Lymphoma

NCT04212013

Description:

The purpose of this study is to see if the combination of rituximab and ibrutinib can help people with marginal zone lymphoma who have not received treatment in the past. The study will also compare the combination of rituximab and ibrutinib with the combination of rituximab and placebo to see which combination works better.

Related Conditions:
  • Marginal Zone Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Ibrutinib With Rituximab in People With Untreated Marginal Zone Lymphoma
  • Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study of Ibrutinib in Combination With Rituximab in Subjects With Treatment Naïve Marginal Zone Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 19-243
  • NCT ID: NCT04212013

Conditions

  • Marginal Zone Lymphoma

Interventions

DrugSynonymsArms
IbrutinibIbrutinib/Placebo
RituximabIbrutinib/Rituximab

Purpose

The purpose of this study is to see if the combination of rituximab and ibrutinib can help people with marginal zone lymphoma who have not received treatment in the past. The study will also compare the combination of rituximab and ibrutinib with the combination of rituximab and placebo to see which combination works better.

Trial Arms

NameTypeDescriptionInterventions
Ibrutinib/RituximabExperimentalAll subjects meeting eligibility criteria will receive rituximab: 375 mg/m2 on days 1, 8, 15 and 22 on cycle 1.
  • Ibrutinib
  • Rituximab
Ibrutinib/PlaceboPlacebo ComparatorIbrutinib capsules (140 mg each) will be dosed at 560 mg once daily on a 28-day cycle on a continuous basis. Placebo capsules will be similarly dosed at 4 capsules daily.
  • Ibrutinib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically documented marginal zone lymphoma, including splenic, nodal, and
             extranodal sub-types at the enrolling institution.

          -  No prior systemic therapy for MZL with the exception of the following:

               -  Prior antibiotic therapy for H. pylori, C. psittaci, and B. burgdorferi

               -  Prior antiviral therapy for HCV Note: Subjects are eligible if they had prior
                  splenectomy or other local surgical treatment without systemic therapy and now
                  require their first ever systemic therapy.

          -  Men and women ≥18 years of age

          -  Patients with gastric MALT lymphoma must be H. pylori negative or have failed a trial
             of H. pylori eradication

          -  Patients with gastric MALT lymphoma who are H. pylori negative or who have
             relapsed/refractory disease after H. pylori eradication must be ineligible for, have
             refused or failed gastric radiation therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

          -  ≥1 measurable lesion on computed tomography (CT) scan (>1.5 cm in longest dimension).
             Lesions in anatomical locations (such as extremities or soft tissue lesions) that are
             not well visualized by CT may be measured by magnetic resonance imaging (MRI) instead.
             Patients with splenomegaly without other measurable disease must have splenomegaly of
             >15 cm in the craniocaudal direction

          -  Life expectancy of >3 months, in the opinion of the investigator

          -  Female subjects must be of non-reproductive potential (i.e., post-menopausal by
             history - no menses for ≥2 years; OR history of hysterectomy; OR history of bilateral
             tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing
             potential must have a negative serum pregnancy test upon study entry

          -  Male and female subjects who agree to use highly effective methods of birth control
             (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine
             devices [IUDs], sexual abstinence, or sterilized partner) during the period of therapy
             and for 30 days (females) and 90 days (males) after the last dose of study drug

          -  Documented evidence of need for treatment, including, but not limited to, threatened
             end-organ function, bulky disease (>5 cm), symptoms, requirement for transfusion or
             growth factor support, or medically significant need for intervention For subjects
             with presumptive evidence of transformation based on clinical assessment of factors
             such as, but not limited to, increasing lactate dehydrogenase (LDH), rapidly worsening
             disease, or frequent B-symptoms, a pre-treatment biopsy is required to rule out large
             cell transformation

        Exclusion Criteria:

          -  Medically apparent central nervous system lymphoma or leptomeningeal disease

          -  History of other malignancies except adequately treated non-melanoma skin cancer,
             curatively treated in-situ cancer, or other solid tumors curatively treated with no
             evidence of disease for ≥2 years

          -  Subject who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior
             to first dose of ibrutinib/placebo or subject who requires continuous treatment with a
             strong CYP3A inhibitor

          -  Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc.,
             or chronic administration of >20 mg/day of prednisone) within 28 days of the first
             dose of study drug

          -  Currently active, clinically significant cardiovascular disease such as uncontrolled
             arrhythmias or Class 3 or 4 congestive heart failure as defined by New York Heart
             Association Functional Classification; or a history of unstable angina, acute coronary
             syndrome, or myocardial infarction within 6 months of prior to screening

          -  Recent infection requiring systemic anti-infective treatment that was completed ≤14
             days before the first dose of study drug

          -  Any uncontrolled active systemic infection

          -  Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia

          -  Hepatitis B (HBV): All subjects must be screened for hepatitis B and C. Subjects with
             a positive polymerase chain reaction for hepatitis B must be on entecavir or
             equivalent therapy as per institutional standard of care. (Hep C patients may be
             enrolled if other parameters precluding hepatic impairment are met. And they are not
             undergoing active therapy for hepatitis C

          -  Human immunodeficiency virus (HIV): NOTE: HIV is a contraindication if the subject has
             an active opportunistic infection (OI) within 12 months and CD4 count is below the
             normal range

          -  Any of the following abnormalities:

               -  Absolute neutrophil count (ANC) <750 cells/mm3 (0.75 x 10^9/L) unless there is
                  documented bone marrow involvement

               -  Platelet count <50,000 cells/mm^3 (50 x 10^9/L) independent of transfusion
                  support unless there is documented bone marrow involvement

               -  Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≥3.0 x upper
                  limit of normal (ULN)

               -  Creatinine >2.0 x ULN or Estimated Glomerular Filtration Rate GFR
                  [Cockcroft-Gault]) <30 mL/min

               -  Hemoglobin <8.0 g/dL

               -  Bilirubin >1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of
                  non-hepatic origin)

               -  PT/INR >1.5 x ULN and PTT (aPTT) >1.5 x ULN

          -  Unable to swallow capsules or disease significantly affecting gastrointestinal
             function such as malabsorption syndrome, resection of the stomach or small bowel, or
             complete bowel obstruction

          -  Major surgery within 4 weeks prior to the first dose of study drug

          -  Any life-threatening illness, medical condition, including uncontrolled diabetes
             mellitus (DM), 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

          -  Lactating or pregnant

          -  Unwilling or unable to participate in all required study evaluations and procedures

          -  Unable to understand the purpose and risks of the study and to provide a signed and
             dated informed consent form (ICF) and authorization to use protected health
             information (in accordance with national and local subject privacy regulations)

          -  Subjects with chronic liver disease with hepatic impairment Child-Pugh class B or C
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:complete response
Time Frame:30 months after randomization
Safety Issue:
Description:per the RECIL criteria

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Ibrutinib
  • Rituximab
  • Treatment Naïve
  • 19-243

Last Updated

December 23, 2019