Clinical trial NCT01980654: Study of Ibrutinib in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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 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

Primary outcomes:
measure: Overall Response Rate (ORR): Proportion of Subjects Achieving the Best Overall Responses of Complete Response (CR) or Partial Response (PR)
timeFrame: 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:
measure: Duration of Response (DOR)
timeFrame: Up to 45 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 45 months
measure: Overall Survival (OS)
timeFrame: Up to 45 months
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: Up to 45 months
Other outcomes:
Locations:
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University, Stanford Care Center
state: California
city: Newnan
country: United States
facility: Southeastern Regional Medical Center
state: Georgia
city: Indianapolis
country: United States
facility: Community Health Network Community Regional Cancer Center North
state: Indiana
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College New York-Presbyterian Hospital
state: New York
city: Columbus
country: United States
facility: Mid-Ohio Oncology/ Hematology Inc
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC The Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Pharmacyclics LLC.
name: Jutta K. Neuenburg, MD, PhD
role: STUDY_DIRECTOR
References: