Study of Ibrutinib in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma

March 26, 2019 updated by: Pharmacyclics LLC.

A Multicenter, Open-Label, Phase 2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma

This is an open-label, Phase 2 study designed to assess the efficacy and safety of ibrutinib combined with rituximab in previously untreated subjects with Follicular Lymphoma (FL).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, Phase 2 study designed to assess the efficacy and safety of ibrutinib combined with rituximab in previously untreated subjects with FL.

There are two study treatment arms.

Subjects enrolled into main study treatment arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.

Subjects enrolled into the exploratory study treatment arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Burbank, California, United States, 91505
        • Providence Saint Joseph Medical Center
      • Duarte, California, United States, 91010
        • City of Hope
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
      • Stanford, California, United States, 94305
        • Stanford University, Stanford Care Center
    • Georgia
      • Newnan, Georgia, United States, 30265
        • Southeastern Regional Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46256
        • Community Health Network Community Regional Cancer Center North
    • Nevada
      • Henderson, Nevada, United States, 89074
        • Comprehensive Cancer Centers of Nevada
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10065
        • Weill Cornell Medical College New York-Presbyterian Hospital
    • Ohio
      • Columbus, Ohio, United States, 43219
        • Mid-Ohio Oncology/ Hematology Inc
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC The Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion criteria:

  1. Histologically documented FL (Grade 1, 2 and 3A)
  2. Not previously treated with prior anti-cancer therapy for FL
  3. Stage II, III or IV disease
  4. At least one measurable lesion ≥ 2 cm in longest diameter by CT and/or MRI scan
  5. Men and women ≥ 18 years of age
  6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

Key Exclusion criteria:

  1. Medically apparent central nervous system lymphoma or leptomeningeal disease
  2. FL with evidence of large cell transformation
  3. Any prior history of other hematologic malignancy besides FL or myelodysplasia

  4. History of other malignancies, except

    1. Malignancy treated with curative intent and with no known active disease present for ≥5 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
    2. Adequately treated non-melanoma skin cancer or lentigomaligna without evidence of disease.
    3. Adequately treated carcinoma in situ without evidence of disease.
  5. Currently active, clinically significant cardiovascular disease or myocardial infarction within 6 months of screening
  6. Known anaphylaxis or Immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab (Rituxan®)
  7. Requires anti-coagulation with warfarin or a vitamin K antagonist.
  8. Requires treatment with strong cytochrome P450 (CYP) 3A inhibitors.
  9. Known bleeding diathesis or hemophilia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Main Study Arm 1
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab once weekly for four doses for the first four weeks of study treatment.
Drug: Ibrutinib
All subjects will receive 560 mg of Ibrutinib orally.
Other Names:
  • PCI-32765
Drug: rituximab
All subjects will receive rituximab 375 mg/m2 intravenously
Other Names:
  • Rituxan
EXPERIMENTAL: Exploratory Study Arm 2
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for the first eight weeks, then ibrutinib concurrently with rituximab once weekly for four doses. After the rituximab treatment, subjects will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Drug: Ibrutinib
All subjects will receive 560 mg of Ibrutinib orally.
Other Names:
  • PCI-32765
Drug: rituximab
All subjects will receive rituximab 375 mg/m2 intravenously
Other Names:
  • Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR): Proportion of Subjects Achieving the Best Overall Responses of Complete Response (CR) or Partial Response (PR)
Time Frame: Subjects in Arm 1 will have imaging assessments every 12 weeks for the first 8 assessments, then every 24 weeks. Subjects in Arm 2 will have imaging assessments starting at week 9, then every 12 weeks for 8 assessments, then every 24 weeks.
Number of subjects achieving the best overall responses of CR or PR prior to the initiation of the next line of antineoplastic therapy as assessed by investigator per the Cheson et al, 2007 criteria. Target lesions are measured by CT, unless MRI is used as the assessment modality for lesions in anatomical locations not amenable to CT. CR is defined as the disappearance of all evidence of disease. PR is defined as >=50% decrease in the sum of the product of the diameters of up to 6 largest dominant masses.
Subjects in Arm 1 will have imaging assessments every 12 weeks for the first 8 assessments, then every 24 weeks. Subjects in Arm 2 will have imaging assessments starting at week 9, then every 12 weeks for 8 assessments, then every 24 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR)
Time Frame: Up to 45 months
DOR is defined as the interval between the date of the first documented response (CR, PR) and the date of the first documented evidence of progressive disease (PD) or death. DOR will be analyzed for the subjects who achieve an overall response during the duration of study.
Up to 45 months
Progression Free Survival (PFS)
Time Frame: Up to 45 months
PFS is defined as the time interval between the date of the first dose and the date of the earliest occurrence of PD or death due to any cause, whichever occurs first. PD is characterized by any new lesion or increase by >=50% of previously involved sites from nadir.
Up to 45 months
Overall Survival (OS)
Time Frame: Up to 45 months
Subjects will be followed for survival information up to three years after the last dose of study treatment, until new treatment or death, whichever occurs first. OS is defined as the duration of time from the date of the first dose to the date of death from any cause.
Up to 45 months
Number of Participants With Treatment-emergent Adverse Events
Time Frame: Up to 45 months
Frequency, severity, and relatedness of treatment-emergent adverse events (AEs) Frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions
Up to 45 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pharmacyclics LLC.

Investigators

  • Study Director: Jutta K. Neuenburg, MD, PhD, Pharmacyclics LLC.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2013

Primary Completion (ACTUAL)

November 1, 2017

Study Completion (ACTUAL)

November 1, 2017

Study Registration Dates

First Submitted

October 24, 2013

First Submitted That Met QC Criteria

November 4, 2013

First Posted (ESTIMATE)

November 11, 2013

Study Record Updates

Last Update Posted (ACTUAL)

April 16, 2019

Last Update Submitted That Met QC Criteria

March 26, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCYC-1125-CA

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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