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

NCT01980654 | Completed Phase 2 Results

• 1 other identifier: PCYC-1125-CA
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 12

Brief Summary

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).

Conditions

Follicular Lymphoma; B-cell Lymphoma; Non-Hodgkin's Lymphoma

Keywords

Pharmacyclics (PCYC); PCYC; Lymphoma; Follicular Lymphoma; FL; Rituximab; Ibrutinib; Rituxan; Non-Hodgkin's Lymphoma (NHL); NHL; B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR): Proportion of Subjects Achieving the Best Overall Responses of Complete Response (CR) or Partial Response (PR)

  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 Outcomes (4)

• Duration of Response (DOR)

  Up to 45 months

• Progression Free Survival (PFS)

  Up to 45 months

• Overall Survival (OS)

  Up to 45 months

• Number of Participants With Treatment-emergent Adverse Events

  Up to 45 months

Study Arms (2)

Main Study Arm 1

EXPERIMENTAL

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; Drug: rituximab

Exploratory Study Arm 2

EXPERIMENTAL

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; Drug: rituximab

Interventions

Ibrutinib DRUG

All subjects will receive 560 mg of Ibrutinib orally.

Also known as: PCI-32765

Exploratory Study Arm 2; Main Study Arm 1

rituximab DRUG

All subjects will receive rituximab 375 mg/m2 intravenously

Also known as: Rituxan

Exploratory Study Arm 2; Main Study Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Medically apparent central nervous system lymphoma or leptomeningeal disease
• FL with evidence of large cell transformation
• Any prior history of other hematologic malignancy besides FL or myelodysplasia
• History of other malignancies, except
• 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.
• Adequately treated non-melanoma skin cancer or lentigomaligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Currently active, clinically significant cardiovascular disease or myocardial infarction within 6 months of screening
• Known anaphylaxis or Immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab (Rituxan®)
• Requires anti-coagulation with warfarin or a vitamin K antagonist.
• Requires treatment with strong cytochrome P450 (CYP) 3A inhibitors.
• Known bleeding diathesis or hemophilia

Sponsors & Collaborators

• Pharmacyclics LLC.: lead

Study Sites (12)

Providence Saint Joseph Medical Center

Burbank, California, 91505, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Stanford University, Stanford Care Center

Stanford, California, 94305, United States

Location

Southeastern Regional Medical Center

Newnan, Georgia, 30265, United States

Location

Community Health Network Community Regional Cancer Center North

Indianapolis, Indiana, 46256, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89074, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical College New York-Presbyterian Hospital

New York, New York, 10065, United States

Location

Mid-Ohio Oncology/ Hematology Inc

Columbus, Ohio, 43219, United States

Location

Tennessee Oncology, PLLC The Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Interventions

ibrutinib; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Jutta Neuenburg
• Organization: Pharmacyclics

jneuenburg@pcyc.com

408-215-3735

Study Officials

• Jutta K. Neuenburg, MD, PhD

  Pharmacyclics LLC.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2013
• First Posted: November 11, 2013
• Study Start: December 1, 2013
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: April 16, 2019
• Results First Posted: April 16, 2019

Record last verified: 2019-03

Locations

US (12)