Ibrutinib in Treating Patients with Refractory or Relapsed Lymphoma after Donor Stem Cell Transplant

Inclusion Criteria

• PRE-STEM CELL TRANSPLANT (SCT)
• Adult (>=18 Years [y]) Patients undergoing their first T-cell replete allogenic (allo)-HCT for chronic lymphocytic leukemia (CLL), Hodgkin Lymphoma (HL), or the following subtypes of non-Hodgkin lymphoma: mantle cell lymphoma (MCL) and follicular center cell lymphoma (FL)
• Meeting institutional criteria for allo-HCT; ejection fraction by echocardiogram or multi-gated acquisition scan (MUGA) > 40%, pulmonary function test with adjusted diffusion capacity of the lung for carbon monoxide (DLCO) >= 60%
• Matched (8/8) or mismatched (7/8) related, unrelated HCT
• Stem cell source: bone marrow, peripheral blood stem cell
• Disease criteria: * Cohort A: ** CLL *** Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm AND *** 17 p deletion (detected by any assay) (>= 20% of cells involved if assay is conventional cytogenetics or fluorescence in situ hybridization [FISH]) or NOTCH mutation at any time point during disease course; patient should have received at least 1 line of therapy; prior ibrutinib therapy is permitted OR *** Relapsed/refractory CLL >= 2 lines of therapy; prior ibrutinib therapy is permitted ** MCL *** Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm *** Relapsed/refractory MCL >= 1 line of therapy; prior ibrutinib therapy is permitted; prior autologous HCT is permitted *** MCL blastoid variant in first complete response (CR1) or high risk MCL being considered for allo HCT in CR1 * Cohort B: ** FL *** Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm AND *** Relapsed/refractory FL >= 2 lines of therapy; prior ibrutinib therapy is permitted ** Hodgkin disease (HD) *** Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm AND *** Relapsed/refractory HD >= 2 lines of therapy
• Preparative regimen: both reduced intensity and ablative regimens are permitted; each center will pre-specify the regimen they intend to use during the conduct of the study
• Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; men must agree to not donate sperm during and after the study; for females, these restrictions apply for 1 month after the last dose of study drug; for males, these restrictions apply for 3 months after the last dose of study drug
• Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening; women who are pregnant or breastfeeding are ineligible for this study
• Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
• Karnofsky performance status (KPS) >= 60% (prior to administration of ibrutinib [day 60 to day 90 post HCT])
• Engraftment of neutrophils (absolute neutrophil count [ANC] >= 1.0 X 10^9/L) for 3 days without granulocyte colony-stimulating factor (g-csf) support (prior to administration of ibrutinib [day 60 to day 90 post HCT])
• Platelets >= 100,000/mm^3 or >= 50,000/mm^3 if bone marrow involvement independent of transfusion support in either situation (prior to administration of ibrutinib [day 60 to day 90 post HCT])
• Glomerular filtration rate (GFR) >= 30 ml/min (prior to administration of ibrutinib [day 60 to day 90 post HCT])
• Liver function tests (LFTs) (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) =< 3 X upper limit of normal (ULN) (prior to administration of ibrutinib [day 60 to day 90 post HCT])
• Total bilirubin =< 1.5 mg/dL X ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin (prior to administration of ibrutinib [day 60 to day 90 post HCT])
• Predominant donor chimerisms of >= 51% as measured by CD3 and CD33 (or other myeloid marker) (prior to administration of ibrutinib [day 60 to day 90 post HCT])
• DONOR CRITERIA: Human leukocyte antigen (HLA) >= 7/8 related or unrelated donors

Exclusion Criteria

• PRE-SCT: Progression of CLL or MCL or FL or HD at time of transplant
• PRE-SCT: Use of Coumadin (warfarin) or other vitamin-K antagonists for anticoagulation; non-Coumadin anticoagulation is permitted
• PRE-SCT: Known central nervous system (CNS) involvement
• PRE-SCT: Active uncontrolled bacterial or invasive fungal infections
• PRE-SCT: History of malignancy other than the underlying disease unless treated with a curative intent and/or no evidence of disease for at least 3 years (y) OR expected to be cured with SCT
• PRE-SCT: Planned use of post-HCT cyclophosphamide for GVHD prophylaxis
• PRE-SCT: Anticipated planned donor lymphocyte infusion in the first 3 months post-SCT
• PRE-SCT: T deplete HCT
• PRE-SCT: Umbilical cord HCT
• PRE-SCT: History of stroke or intracranial hemorrhage within 6 months of enrollment
• PRE-SCT: Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• PRE-SCT: Known human immunodeficiency syndrome (HIV)
• PRE-SCT: Active hepatitis B or C virus
• PRE-SCT: Child-Pugh class C
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT)
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): In the critical care unit, or use of mechanical ventilation or use of renal replacement therapy at any time post HCT and prior to administration of ibrutinib
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Active uncontrolled stage 3-4 acute gastrointestinal (GI) GVHD prior to administration of ibrutinib
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Active uncontrolled stage 4 acute liver GVHD prior to administration of ibrutinib
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Evidence of progressive disease as compared to pre-HCT (persistence of disease is permitted)
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Anticipated planned donor lymphocyte infusion in the first 3 months post-SCT
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Active uncontrolled bacterial or invasive fungal infections
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Prednisone equivalent of > 2m/kg for treatment of GVHD prior to administration of ibrutinib
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Use of second line systemic therapy for treatment of acute GVHD prior to administration of ibrutinib
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): 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 including the presence of chronic/active hepatitis B virus (HBV) and hepatitis C virus (HBC) infections and Child-Pugh class C
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Major surgery or a wound that has not fully healed within 4 weeks of starting ibrutinib
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon)
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Requires chronic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors
• PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT): Vaccinated with live, attenuated vaccines within 4 weeks of starting ibrutinib