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

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).

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.

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