Ibrutinib After Intensive Induction in Treating Patients With Previously Untreated Mantle Cell Lymphoma

PRIMARY OBJECTIVES:

I. To determine the progression-free survival (PFS) rate after 2 years.

SECONDARY OBJECTIVES:

I. Assess toxicity. II. Determine rates of conversion from partial response (PR) to complete
response (CR).

III. Determine median overall survival (OS) after 4 years.

TERTIARY OBJECTIVES:

I. Compare minimal residual disease (MRD) results overtime by polymerase chain reaction (PCR)
and correlate these with PFS and OS.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28
days for up to 4 years in the absence of disease progression, unacceptable toxicity or
patient preference.

After completion of study treatment, patients who completed 4 years of treatment are followed
up at 30 days. Patients who did not complete 4 years of treatment are followed up for up to 4
years post-first dose of treatment (every 3 months for 2 years and then every 6 months for 4
years).

Inclusion Criteria:

- Patients must have histologically confirmed mantle cell lymphoma (MCL)

- Please note: Measurable disease is not required, but will be followed if it
exists

- Patients must have received 4 or more cycles of one of the following prior systemic
induction chemotherapy regimens:

- Rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin),
vincristine sulfate (Oncovin), prednisone (R-CHOP) (with or without alternating
rituximab, dexamethasone, cytarabine [ara-c], cisplatin [platinum] [R-DHAP]) with
or without autologous (auto) stem cell transplant (SCT)

- Hyper-cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride
(adriamycin), dexamethasone (CVAD) with or without auto SCT

- Bendamustine + rituximab with or without auto SCT

- Please note:

- Patients who received combinations of the above regimens are not
eligible for enrollment

- At the time of registration, patients must be at least 14 days out from
last dose of cytotoxic chemotherapy, but no more than 90 days; if a
patient underwent auto SCT, he/she must demonstrate engraftment (per
treating investigator's discretion) and must meet all other
hematological requirements as outlined below

- Patients must have achieved a response to induction chemotherapy (either CR or PR by
Cheson 2007 criteria) and be without known progression

- Patients may have received prior radiotherapy

- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status
=< 2

- Absolute neutrophil count (ANC) >= 1000/mm^3, independent of growth factor support

- Platelets >= 100,000/mm^3, or >= 50,000 in cases of ongoing bone marrow involvement
(in either case, these must be independent of transfusion support)

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT])
=< 3 x ULN

- Creatinine clearance >= 25 ml/min

- Please note: Patients who do not meet the above criteria because of Gilbert's Syndrome
are still eligible

- Women of child-bearing potential (WOCBP) 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 (see timelines below for women and
men); in addition, men must agree not to donate sperm during and after study
participation; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately

- NOTE: For female patients, these restrictions apply for 1 month after the last
dose of study drug; for male patients, these restrictions apply for 3 months
after the last dose of study drug

- NOTE: A female of child-bearing potential is any woman (regardless of sexual
orientation, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 12 consecutive months
(i.e., has had menses at any time in the preceding 12 consecutive months)

- Female patients must have a negative pregnancy test (blood or urine) within 28 days
prior to registration

- Patients must be willing and able to avoid consuming food and beverages containing
grapefruit or Seville oranges while on ibrutinib study therapy

- Patients must have the ability to understand and the willingness to sign a written
informed consent prior to registration on study

Exclusion Criteria:

- Patients who have received >= 7 days of prior ibrutinib or any prior treatment with
another Bruton tyrosine kinase (BTK) inhibitor are not eligible

- Patients receiving ongoing treatment with any other investigational agents are not
eligible

- Patients receiving live/attenuated vaccinations within 4 weeks prior to registration
are not eligible

- Patients with a known central nervous system (CNS) involvement of lymphoma are not
eligible (CNS staging not required)

- Patients who have undergone major surgery within 4 weeks prior to registration are not
eligible

- Patients diagnosed or treated for malignancy other than MCL are not eligible unless
they meet one of the following exceptions:

- Malignancy treated with curative intent and with no known active disease present
for >= 3 years before registration and felt to be at low risk for recurrence by
the treating physician

- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease

- Adequately treated cervical carcinoma in situ without evidence of disease

- Patients with a history of stroke or intracranial hemorrhage within 6 months prior to
registration are not eligible

- Patients who require anticoagulation with warfarin or equivalent vitamin K antagonists
are not eligible

- Patients who require chronic treatment with strong cytochrome P450, family 3,
subfamily A, polypeptide 4/5 (CYP3A4/5) inhibitors are not eligible

- NOTE: Patients who are currently on treatment with strong CYP3A4/5 inhibitors may
be eligible if they are able to be switched to an alternative therapy that is not
a strong CYP3A4/5 inhibitor prior to registration on study

- Patients with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to ibrutinib are not eligible

- Patients with uncontrolled intercurrent illness including, but not limited to, any of
the following are not eligible:

- Ongoing or active systemic infection

- Symptomatic congestive heart failure

- Myocardial infarction within 6 months prior to registration

- Unstable angina pectoris

- Uncontrolled or symptomatic cardiac arrhythmias

- Any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New
York Heart Association Functional Classification

- Psychiatric illness/social situations that would limit compliance with study
requirements

- Patients who have any life-threatening illness, medical condition, or organ system
dysfunction which, in the investigator's opinion, could compromise the subject's
safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the
study outcomes at risk are not eligible

- Patients with a known human immunodeficiency virus (HIV) infection are not eligible
(HIV testing not required)

- Patients with a known John Cunningham (JC) virus infection and/or progressive
multifocal leukoencephalopathy (PML) are not eligible

- Patients with clinically active hepatitis A, B, or C infections are not eligible

- Female patients who are pregnant and/or lactating are not eligible