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

Sponsor
Memorial Sloan Kettering Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT04212013
Collaborator
Pharmacyclics LLC. (Industry)
138
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2
86.8
10.6
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Study Details

Study Description

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
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
138 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
This is a Phase III randomized, double-blind, placebo controlled, multicenter.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 :
Dec 23, 2019
Anticipated Primary Completion Date :
Jun 30, 2024
Anticipated Study Completion Date :
Mar 18, 2027

Arms and Interventions

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

Primary Outcome Measures

  1. complete response [30 months after randomization]

    per the RECIL criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 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, 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/mm3 (50 x 109/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

Locations

Site City State Country Postal Code
1 University of California, Los Angeles Los Angeles California United States 90095
2 George Washington Cancer Center Washington District of Columbia United States 20037
3 Moffitt Cancer Center Tampa Florida United States 33612
4 Northwestern Medicine (Robert H Lurie Cancer Center) Chicago Illinois United States 60611
5 Mayo Clinic Cancer Center Rochester Minnesota United States 55905
6 Memorial Sloan Kettering Basking Ridge Basking Ridge New Jersey United States 07920
7 Memorial Sloan Kettering Monmouth Middletown New Jersey United States 07748
8 Memorial Sloan Kettering Bergen Montvale New Jersey United States 07645
9 Memorial Sloan Kettering Commack Commack New York United States 11725
10 Memorial Sloan Kettering Westchester Harrison New York United States 10604
11 Memorial Sloan Kettering Cancer Center New York New York United States 10065
12 Memorial Sloan Kettering Nassau Uniondale New York United States 11553
13 Medical College of Wisconsin (Data collection only) Milwaukee Wisconsin United States 53226

Sponsors and Collaborators

  • Memorial Sloan Kettering Cancer Center
  • Pharmacyclics LLC.

Investigators

  • Principal Investigator: Ariela Noy, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT04212013
Other Study ID Numbers:
  • 19-243
First Posted:
Dec 26, 2019
Last Update Posted:
Mar 10, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 10, 2022