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

Phase 2CompletedNCT01980654

Pharmacyclics LLC.80 enrolled

Overview

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).

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

IbrutinibDRUG

All subjects will receive 560 mg of Ibrutinib orally.

rituximabDRUG

All subjects will receive rituximab 375 mg/m2 intravenously

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (12)

Providence Saint Joseph Medical Center

Burbank, California, United States

City of Hope

Duarte, California, United States

UCLA Medical Center

Los Angeles, California, United States

Outcomes

Primary Outcomes

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.

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.

Secondary Outcomes

Duration of Response (DOR)

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.

Time frame: Up to 45 months

Progression Free Survival (PFS)

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.

Time frame: Up to 45 months

Overall Survival (OS)

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.

Time frame: Up to 45 months

Data from ClinicalTrials.gov

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