Ibrutinib in Treating Patients With Relapsed or Refractory Follicular Lymphoma
Condition: Grade 3a Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Refractory Follicular Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular; Recurrence
Intervention: Ibrutinib; Laboratory Biomarker Analysis
Intervention description: Given PO; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well ibrutinib works in treating patients with follicular
      lymphoma that has come back after a period of improvement or does not respond to treatment.
      Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell
      growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of follicular lymphoma, grade 1, 2, or 3a

               -  Note: Fresh (frozen) tumor biopsy must be available or attempted; a frozen tumor
                  biopsy equivalent to a minimum of four at least 16 gauge needle cores is an
                  important component of this study; patients without adequate frozen material
                  should have a biopsy performed to obtain material; if biopsy is performed and
                  does not yield adequate material, the patient is still eligible for the study; if
                  a biopsy cannot be done safely, the patient may still be eligible for the study
                  if permission is granted in writing (email) by the study chair (Dr. Nancy
                  Bartlett) or her designees; Dr. Bartlett may be consulted to discuss situations
                  involving invasive biopsy procedures that may pose an increased risk to the
                  patient

          -  Measurable disease as defined by a lymph node or tumor mass that is >= 1.5 cm in at
             least one dimension by CT or the CT portion of the PET/CT

          -  Relapsed or refractory follicular lymphoma which has progressed during or following 1
             or more prior chemotherapy regimens for lymphoma

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

          -  Absolute neutrophil count >= 750/mm^3 (0.75 x 10^9/L)

          -  Hemoglobin >= 8.0 g/dL

          -  Platelets >= 30,000/mm^3 (30 x 10^9/L)

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless Gilbert's
             syndrome or disease infiltration of the liver is present

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.0 x institutional ULN

          -  Creatinine =< 2.0 x institutional ULN

          -  Creatinine clearance (estimated [est.] glomerular filtration rate [GFR]
             Cockcroft-Gault) >= 30 mL/min

          -  Negative serum pregnancy test done =< 7 days prior to registration for women of
             childbearing potential only

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Willingness to provide biologic samples for correlative research purposes

        Exclusion Criteria:

          -  Any of the following:

               -  Chemotherapy/systemic therapy =< 4 weeks prior to registration

               -  Radiotherapy =< 4 weeks prior to registration

               -  Nitrosoureas or mitomycin C =< 6 weeks prior to registration

               -  Those who have not recovered from adverse events due to agents administered more
                  than 4 weeks earlier

               -  Major surgery =< 10 days prior to registration or minor surgery =< 7 days prior
                  to registration

               -  Prior therapy with ibrutinib or another Bruton's tyrosine kinase inhibitor

               -  Receiving any other investigational agents

          -  Active central nervous system (CNS) involvement

          -  Receiving any medications or substances that are strong inhibitors or inducers of
             cytochrome P450 family 3 subfamily A member 4/5 (CYP3A4/5)

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

                    -  Note: Women of child-bearing potential and men must agree to use adequate
                       contraception (hormonal or barrier method of birth control; abstinence)
                       prior to study entry and for the duration of study participation; should a
                       woman become pregnant or suspect she is pregnant while she or her partner is
                       participating in this study, she should inform her treating physician
                       immediately; men treated or enrolled on this protocol must also agree to use
                       adequate contraception prior to the study, for the duration of study
                       participation, and 4 months after completion of ibrutinib administration

                    -  Note: Breastfeeding should be discontinued if the mother is treated with
                       ibrutinib

          -  Human immunodeficiency virus (HIV)-positive patients on antiretroviral therapy are
             ineligible; appropriate studies will be undertaken in patients receiving combination
             antiretroviral therapy when indicated

               -  Note: HIV-positive patients who are not on anti-viral medications that are strong
                  CYP3A4/5 inhibitors and who do not have cluster of differentiation (CD)4 counts
                  less than the lower limit of normal by institutional criteria are eligible; no
                  patients with CD4 counts below institutional normals are eligible

          -  Known active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)

          -  Known histological transformation from follicular lymphoma to diffuse large B-cell
             lymphoma

               -  Note: A prior history of adequately treated transformed lymphoma does not exclude
                  a patient if the current active disease is biopsy-proven follicular lymphoma

          -  History of stroke or intracranial hemorrhage =< 6 months prior to the first dose of
             study drug

          -  Requires anticoagulation with warfarin or similar vitamin K antagonist

               -  Note: Warfarin or similar vitamin K antagonist must have been discontinued at
                  least 28 days prior to study entry

          -  Patient has the inability to swallow tablets

          -  Uncontrolled intercurrent illness including, but not limited to:

               -  Ongoing or active infection,

               -  Uncontrolled diabetes mellitus

               -  Cardiac disease

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

          -  "Currently active" second malignancy, other than non-melanoma skin cancers

               -  Note: Patients are not considered to have a "currently active" malignancy if they
                  have completed anti-cancer therapy, and are considered by their physician to be
                  at less than 30% risk of relapse

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ibrutinib

          -  Concurrent treatment with therapeutic doses (> 20 mg prednisone or equivalent) of
             systemic steroids within 14 days of start of protocol therapy

          -  Prior history of allogeneic stem cell transplant