Study of the Bruton's Tyrosine Kinase Inhibitor in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Pharmacyclics
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01980654
First received: October 24, 2013
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Follicular Lymphoma
B-cell Lymphoma
Non-Hodgkin's Lymphoma
Drug: Ibrutinib
Drug: rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • To evaluate the efficacy of ibrutinib when combined with rituximab (determined by the overall response rate [ORR]) in previously untreated subjects with FL. [ Time Frame: When last subject enrolled has completed 3 years of study follow-up ] [ Designated as safety issue: No ]

    Subjects in Arm 1 will have imaging efficacy assessments every 12 weeks for the first 8 assessments and then every 16 weeks thereafter.

    Subjects in Arm 2 will have imaging efficacy assessments at the end of 8 weeks and then every 12 weeks thereafter for 8 assessments and then every 16 weeks thereafter.



Secondary Outcome Measures:
  • To evaluate the efficacy of ibrutinib combined with rituximab in subjects with FL as assessed by the duration of response (DOR). [ Time Frame: When last subject enrolled has completed 3 years of study follow-up ] [ Designated as safety issue: No ]
    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.

  • To evaluate the efficacy of ibrutinib combined with rituximab in subjects with FL as assessed by progression free survival (PFS). [ Time Frame: When last subject enrolled has completed 3 years of study follow-up ] [ Designated as safety issue: No ]
    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.

  • To evaluate the efficacy of ibrutinib combined with rituximab in subjects with FL as assessed by overall survival (OS). [ Time Frame: When last subject enrolled has completed 3 years of study follow-up ] [ Designated as safety issue: No ]
    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.

  • To evaluate the safety and tolerability of ibrutinib combined with rituximab in previously untreated subjects with FL [ Time Frame: When last subject enrolled has completed 3 years of study follow-up ] [ Designated as safety issue: Yes ]
    Frequency, severity, and relatedness of treatment-emergent adverse events (AEs) Frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions


Estimated Enrollment: 80
Study Start Date: December 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Main Study Arm
Subjects enrolled into this arm will receive ibrutinib continuously until disease progression or unacceptable toxicity. In addition, subjects will receive rituximab weekly for the first four weeks of study treatment.
Drug: Ibrutinib
All subjects will receive 560 mg of Ibrutinib orally.
Other Name: PCI-32765
Drug: rituximab
All subjects will receive rituximab 375mg/m2 intravenously
Other Name: Rituxan
Experimental: Exploratory Study Arm
Subjects enrolled into this arm will receive ibrutinib continuously as a single agent for eight weeks, then ibrutinib concurrently with rituximab weekly for four weeks. After the rituximab treatment, patients will receive ibrutinib continuously until disease progression or unacceptable toxicity.
Drug: Ibrutinib
All subjects will receive 560 mg of Ibrutinib orally.
Other Name: PCI-32765
Drug: rituximab
All subjects will receive rituximab 375mg/m2 intravenously
Other Name: Rituxan

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 CYP3A4/5 inhibitors.
  9. Known bleeding diathesis or hemophilia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01980654

Contacts
Contact: Vina Truong 855-427-8846 medinfo@pcyc.com

Locations
United States, Ohio
Mid-Ohio Oncology/ Hematology Inc Recruiting
Columbus, Ohio, United States, 43219
Contact    866-926-4236    contact@zangcenter.com   
United States, Texas
The University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pharmacyclics
Investigators
Study Director: Jutta K. Neuenburg, MD, PhD Pharmacyclics
  More Information

No publications provided

Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT01980654     History of Changes
Other Study ID Numbers: PCYC-1125-CA
Study First Received: October 24, 2013
Last Updated: January 8, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Pharmacyclics:
Pharmacyclics
PCYC
Lymphoma
Follicular Lymphoma
FL
Rituximab
Ibrutinib
Rituxan
Non-Hodgkin's Lymphoma
NHL
B-cell Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014