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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04212013
Recruitment Status : Recruiting
First Posted : December 26, 2019
Last Update Posted : March 17, 2023
Sponsor:
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Marginal Zone Lymphoma Drug: Ibrutinib Drug: Rituximab Other: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a Phase III randomized, double-blind, placebo controlled, multicenter.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 23, 2019
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : March 18, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Ibrutinib/Rituximab
All subjects meeting eligibility criteria will receive rituximab: 375 mg/m^2 on days 1, 8, 15 and 22 on cycle 1.
 Drug: Ibrutinib
Ibrutinib capsules (140 mg each) will be dosed at 560 mg once daily on a 28-day cycle on a continuous basis.

Drug: Rituximab
Will receive rituximab: 375 mg/m^2 on days 1, 8, 15 and 22 of cycle 1
Placebo Comparator: Ibrutinib/Placebo
Ibrutinib 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.
 Drug: Ibrutinib
Ibrutinib capsules (140 mg each) will be dosed at 560 mg once daily on a 28-day cycle on a continuous basis.

Other: Placebo
Placebo capsules will be similarly dosed at 4 capsules daily.


Outcome Measures
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Primary Outcome Measures :
  1. complete response [ Time Frame: 30 months after randomization ]
    per the RECIL criteria


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 or local radiation therapy 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) unless bone marrow disease only including those with hemolytic anemia. 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 12 months (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, both a pre-treatment tumor biopsy and bone marrow biopsy are required to rule out large cell transformation. For all subjects, results of both the tumor biopsy and bone marrow biopsy must be known prior to enrollment and randomization.

Exclusion Criteria:

  • Medically apparent central nervous system lymphoma or leptomeningeal disease
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible
  • 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 unless secondary to hemolysis or documented bone marrow involvement
    • 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 unless factor XI deficiency or lupus anticoagulant.
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04212013


Contacts
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Contact: Ariela Noy, MD 646-608-3727 noya@mskcc.org
Contact: Lia Palomba, MD 646-608-3711

Locations
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United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Sven de Vos, MD    310-829-5471      
United States, District of Columbia
George Washington Cancer Center Not yet recruiting
Washington, District of Columbia, United States, 20037
Contact: Kieron Dunleavy, MD    202-741-2210      
United States, Florida
Moffitt Cancer Center Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Sameh Gaballa, MD    813-745-6100      
United States, Illinois
Northwestern Medicine (Robert H Lurie Cancer Center) Recruiting
Chicago, Illinois, United States, 60611
Contact: Shou Ma, MD, PhD    312-695-0990      
United States, Minnesota
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Thomas Habermann, MD    507-538-3270      
United States, New Jersey
Memorial Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Ariela Noy, MD    646-608-3727      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Ariela Noy, MD    646-608-3727      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Ariela Noy, MD    646-608-3727      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Ariela Noy, MD    646-608-3727      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Ariela Noy, MD    646-608-3727      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Ariela Noy, MD    646-608-3727      
Contact: Lia Palomba, MD    646-608-3711      
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Ariela Noy, MD    646-608-3727      
United States, Wisconsin
Medical College of Wisconsin (Data collection only) Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Timothy Fenske, MD, MS    414-805-3666      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Pharmacyclics LLC.
Investigators
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Principal Investigator: Ariela Noy, MD Memorial Sloan Kettering Cancer Center
More Information
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Additional Information:

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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04212013    
Other Study ID Numbers: 19-243
First Posted: December 26, 2019    Key Record Dates
Last Update Posted: March 17, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Ibrutinib
Rituximab
Treatment Naïve
19-243
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
 Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents