|Principal Investigator: Deborah Stephens|
|Keywords: CLL Lymphoma||Department: Hematology|
|IRB Number: 00087891|
|Recruitment Status: Recruiting|
Primary Objective & Endpoint
The primary objective will be to determine the progression-free survival (PFS) rate after 3 years.
Progression-free survival (PFS) will be defined as the absence of disease progression or death from any cause. The rate of PFS will be calculated after 3 years.
Secondary Objectives & Endpoints
Secondary objectives will include the following:
- 2.2.1 Assess toxicity. Adverse events will be defined according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. The occurrence and severity of each will be recorded.
- 2.2.2 Determine rates of conversion from PR to CR. The rate of conversion from PR to CR will be calculated based on Cheson 2007 criteria.
- 2.2.3 Determine median overall survival (OS) after 4 years. Patients will be evaluated monthly for the first 6 months on treatment, then every 3 months thereafter. Patients who go off treatment will continue to be followed for survival up to a maximum of 4 years post-first dose. Follow-up will occur every 3 months (up to 2 years after the first dose of treatment) and then every 6 months thereafter (up to 4 years post-first dose). Median OS after 4 years will be calculated.
Exploratory Objectives & Endpoints
Compare MRD results overtime by PCR and correlate these with PFS and OS. We will obtain archived tissue (FFPE slides) from a previous biopsy from all patients for baseline clone identification; in addition, we will collect peripheral whole blood samples at baseline, 1 month after first dose, 6 months after first dose, and approximately 18-24 months after first dose. MRD analysis will be conducted using PCR methods and results will be compared over time and correlated with PFS and OS.
- Patients must have histologically confirmed MCL
Please note: Measureable 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:
- R-CHOP (with or without cytarabine-containing cycles, including “Nordic” and MCL-NET protocols) [1, 2]) with or without auto SCT
- Hyper-CVAD with or without auto SCT
- Bendamustine + rituximab with or without auto SCT
- Patients are allowed to receive combinations of the above regimens.
- 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 meet all other hematological requirements as outlined in the protocol.
- 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 be age ≥ 18 years.
- Patients must exhibit an ECOG performance status ≤ 2.
- Patients must demonstrate adequate organ and marrow function (as defined in the protocol) documented within 14 days of registration:
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 (as these contain certain ingredients that inhibit CYP3A4/5 enzymes) 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.
1. Patients who have received ≥ 7 days of prior ibrutinib or any prior treatment with another BTK inhibitor are not eligible.
2. Patients receiving ongoing treatment with any other investigational agents are not eligible.
3. Patients receiving live/attenuated vaccinations within 4 weeks prior to registration are not eligible.
4. Patients with a known CNS involvement of lymphoma are not eligible (CNS staging not required).
5. Patients who have undergone major surgery within 4 weeks prior to registration are not eligible.
6. 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.
7. Patients with a history of stroke or intracranial hemorrhage within 6 months prior to registration are not eligible.
8.Patients who require anticoagulation with warfarin or equivalent vitamin K antagonists are not eligible.
9. Patients who require chronic treatment with strong CYP3A4/5 inhibitors are not eligible.
NOTE: See Appendix I for examples of such medications. 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.
10. Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib are not eligible.
11.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.
12. 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.
13. Patients with a known HIV infection are not eligible (HIV testing not required).
14. Patients with a known JC virus infection and/or progressive multifocal leukoencephalopathy (PML) are not eligible.
15. Patients with clinically active hepatitis A, B, or C infections are not eligible.
Note: Patients with a history of hepatitis may be eligible if they have a normal titer. Such cases should be approved by the study PI.
16. Female patients who are pregnant and/or lactating are not eligible.