Ibrutinib in Treating Patients With Relapsed or Refractory Follicular Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 19 December 2016
• Main ID: NCT02989532
• Date of registration: 08/12/2016
• Prospective Registration: No
• Primary sponsor: Mayo Clinic
• Public title: Ibrutinib in Treating Patients With Relapsed or Refractory Follicular Lymphoma
• Scientific title: Phase 2 Trial of Single-Agent Ibrutinib (PCI-32765) in Relapsed or Refractory Follicular Lymphoma
• Date of first enrolment: April 2013
• Target sample size: 41
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02989532
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Canada, Singapore, United States

Contacts

• Name: Nancy Bartlett
• Affiliation: Mayo Clinic

Key inclusion & exclusion 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

- Measureable 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 combination antiretroviral
therapy; 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Recurrent Grade 2 Follicular Lymphoma

Refractory Follicular Lymphoma

Recurrent Grade 1 Follicular Lymphoma

Recurrent Grade 3 Follicular Lymphoma

Intervention(s)

Other: Laboratory Biomarker Analysis

Drug: Ibrutinib

Primary Outcome(s)

Overall response rate defined as a partial response (PR) or complete response (CR) as the objective status at any time during treatment, evaluated using the Cheson et al. Revised Response Criteria for Malignant Lymphoma [Time Frame: Up to 5 years]

Secondary Outcome(s)

Duration of response [Time Frame: Time from the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression is documented, assessed up to 5 years]

Time to response [Time Frame: Time from the date of registration to the date at which the patient's objective status is first noted to be a CR or PR, assessed up to 5 years]

Overall survival [Time Frame: Time from registration to death due to any cause, assessed up to 5 years]

Progression-free survival [Time Frame: Time from registration to progression or death due to any cause, assessed up to 5 years]

Time to subsequent treatment [Time Frame: Time from registration to the date of initiation of subsequent treatment for lymphoma, assessed up to 5 years]

Time to treatment failure [Time Frame: Time from registration to the date of treatment discontinuation due to any reason, assessed up to 5 years]

Secondary ID(s)

P30CA015083

NCI-2013-00887

9271

MC1282

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)