| Eligibility |
Inclusion Criteria:
1. Relapsed refractory central nervous system lymphoma, pathology confirmed B cell
lymphoma either by biopsy or by CSF review. Patient must previously have had at least
one line of systemic therapy for CNS lymphoma.
2. Age 18 years or older
3. Eastern Cooperative Oncology Group (ECOG) Performance Status =2
4. Patients must have adequate renal and hepatic function
- Total bilirubin =1.5 x upper limit of normal (ULN). For patients with Gilbert's
disease, total bilirubin up to =3 x ULN is allowed provided normal direct
bilirubin.
- Serum creatinine =1.5 x ULN
- ALT and AST =3 x ULN
5. Females of childbearing potential must have a negative serum or urine beta human
chorionic gonadotrophin (ß-hCG) pregnancy test result within 24 hours prior to the
first dose of treatment and must agree to use a highly effective contraception method
during the study and for 23 weeks following the last dose of the study drugs. Females
of non- childbearing potential are those who are postmenopausal greater than 1 year or
who have had a bilateral tubal ligation or hysterectomy. Males who have partners of
childbearing potential must agree to use an effective contraceptive method during the
study and for 31 weeks following the last dose of study drugs. Men must agree not to
donate sperm during and for 3 months after the last dose of study drug. Women who are
pregnant or breastfeeding are ineligible for this study.
6. Patients or their legally authorized representative must provide written informed
consent.
7. Hematology values must be within the following limits:
1. Absolute neutrophil count (ANC) 1000/mm3 independent of growth factor support
2. Platelets 100,000/mm3 or 50,000/mm3 if bone marrow involvement independent of
transfusion support in either situation
8. Creatinine clearance (CrCl) > 30 ml/min
Exclusion Criteria:
1. History of another primary invasive malignancy that has not been definitively treated
or in remission for at least 2 years. Patients with non-melanoma skin cancers or with
carcinomas in situ are eligible regardless of the time from diagnosis (including
concomitant diagnoses). If patients have another malignancy that was treated within
the last 2 years, such patients may be enrolled if the likelihood of requiring
systemic therapy for this other malignancy within 2 years is less than 10%, as
determined by an expert in that particular malignancy at MD Anderson Cancer Center and
after consultation with the Principal Investigator
2. Any major surgery or wound that has not healed, radiotherapy, cytotoxic chemotherapy,
biologic therapy, immunotherapy, immunomodulatory drugs, experimental therapy within 4
weeks prior to the first dose of the study drugs.
3. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias,
congestive heart failure, 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.
4. History of stroke or cerebral hemorrhage within 6 months of enrollment.
5. Patients who have uncontrolled hypertension (defined as sustained systolic blood
pressure = 160 mmHg or diastolic = 100 mmHg)
6. Prior history of BTK inhibitor or PD1 inhibitor prior to start of trial.
7. Active, uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring
steroid therapy.
8. Patients with autoimmune diseases are excluded: Patients with a history of
Inflammatory Bowel Disease (including Crohn's disease and ulcerative colitis) are
excluded from this study as are patients with a history of autoimmune disease (e.g.,
rheumatoid arthritis, systemic progressive sclerosis, systemic lupus erythematosus,
Wegener's granulomatosis).
9. Patients with previous allogeneic stem cell transplant (SCT) within 6 months or with
active acute or chronic graft-versus host disease are excluded. Patients must be off
immunosuppression for GVHD for at least 30 days before cycle 1 day 1.
10. Patients with organ allografts (such as renal transplant) are excluded.
11. History of biopsy proven interstitial lung disease or pneumonitis which has impacted
PFT in a clinically significant manner.
12. Patients who are on high dose steroids (>10mg daily of prednisone or equivalent) or
immune suppression medications. Note: Patients on high-dose steroids (doses >10mg/day
of prednisone or equivalent) or immune suppression medications are eligible provided
these drugs are discontinued at least 3 days prior to starting on the study drugs.
13. Patients with uncontrolled active infection (viral, bacterial, and fungal) are not
eligible.
14. Active current hepatitis B or C infection/reactivation as measured by DNA/RNA
quantification, or known seropositivity for HIV.
15. Patient is pregnant or breast-feeding.
16. Malabsorption syndrome or other condition that precludes enteral route of
administration.
17. Concomitant use of warfarin or other Vitamin K antagonists.
18. Requires chronic treatment with a strong cytochrome P450 (CYP) 3A inhibitor (see
Appendix 3).
19. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that in the opinion of the investigator may increase the risk associated
with study participation or investigational product administration or may interfere
with the interpretation of study results and/or would make the patient inappropriate
for enrollment into this study.
20. Vaccinated with live, attenuated vaccines within 4 weeks of enrollment.
21. 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 undue
risk.
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