Follicular Lymphoma, Follicular Lymphoma, Grade 1, Follicular Lymphoma, Grade 2, Follicular Lymphoma Grade IIIa
Conditions
Keywords
follicular lymphoma, Ibrutinib, FLIPP, 16-396
Brief summary
The purpose of this study is to find out how successful ibrutinib is at putting follicular lymphoma into full remission. In this study, remission will be determined by achieving a normal PET scan after treatment. A PET scan is an imaging test that looks for active lymphoma. People who don't have a complete remission on PET after their first treatment are at high risk for having their lymphoma return. This study will investigate if ibrutinib will help participants achieve a complete remission without giving additional chemotherapy. The study will also investigate any possible side effects of the study drug ibrutinib.
Interventions
DRUGIbrutinib
Ibrutinib will be administered orally, on a once daily continuous dosing schedule and in an outpatient setting. Treatment will continue for 2 years and there will be no planned treatment breaks. The dose of Ibrutinib will be initiated at 560mg per day, which will remain constant throughout the study period, unless otherwise specified.
Sponsors
Fox Chase Cancer Center
Pharmacyclics LLC.
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Follicular lymphoma with histology documented by the participating institution (grades 1, 2 or 3a). °For subjects with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase (LDH), rapidly worsening disease, or frequent B-symptoms, a pre-treatment biopsy is required to rule out large cell transformation * Completion of a full course of first line immunochemotherapy including rituximab OR completion of 4 cycles of first line immunochemotherapy including rituximab if intolerant (e.g. which include, but are not limited to, R-CHOP, R-CVP, Bendamustine-R). * Patients must have achieved PR to primary treatment and not be refractory to prior treatment. * Residual FDG-PET activity defined as Deauville 4 or 5 on a PET-CT within 3 and 8 weeks post the last dose of front line therapy. * Treatment must begin within 90 days of the last dose of immunochemotherapy. * Men and women ≥ 18 years of age. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. * ≥ 1 measurable disease site on computed tomography (CT) scan or positron emission tomography (PET) (1.5 cm in longest dimension). (In select cases, for example extremity lesions, an MRI may be substituted.) * Life expectancy of \> 3 months, in the opinion of the investigator. * Female subjects who are of non-reproductive potential (i.e. post-menopausal by history - no menses for ≥ 2 years; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry. * Male and female subjects who agree to use highly effective methods of birth control (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence, or sterilized partner) and a barrier method (e.g. condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days (females) and 90 days (males) after the last dose of study drug.
Exclusion criteria
* Medically apparent central nervous system lymphoma or leptomeningeal disease. * History of any other active malignancies. * History of any prior cancer curatively treated within the last two years except: * Any non-melanoma skin cancer * Any cancer excised, not treated with chemotherapy and with less than a 30% chance of recurrence within the next 2 years from registration * History of any organ transplantation. * History of stroke or intracranial hemorrhage within 6 months prior to enrollment. * More than one prior line of any systemic chemoimmunotherapy for follicular lymphoma. * Chemotherapy ≤ 21 days prior to first administration of study treatment and/or monoclonal antibody ≥ 3 weeks prior to first administration of study treatment. * Prior exposure to radio- or toxin-immunoconjugates. * Concurrent use of warfarin or other vitamin K antagonists. * Concurrent use of a strong cytochrome P450 (CYP)3A4/5 inhibitor. * Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration of \> 20 mg/day of prednisone) within 28 days of the first dose of study drug. * Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug. * Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) \>/= 470 msec. * Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure (new York Heart Association \>Class 2), unstable angina, uncontrolled hypertension, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. * Any uncontrolled active systemic infection or recent infection requiring intravenous anti-infective treatment that was complete ≤ 14 days before the first dose of study drug. * Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.0), Grade 0 or 1, or to the levels dictated in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of conversion from FDG-PET positive to negative | 12 months | The primary objective is to determine the rate of conversion from FDG-PET positive to negative at 12 months from the start of ibrutinib in patients receiving at least 6 months of Ibrutinib consolidation therapy for follicular lymphoma achieving at least a PR but remaining FDG-PET positive after first line chemoimmunotherapy. |
Countries
United States
Outcome results
None listed