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Clinical Trials Search at Vanderbilt-Ingram Cancer Center

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

This phase II trial studies how well ibrutinib works in treating patients after a donor stem cell transplant for lymphoma that is not responding to treatment or has come back. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Leukemia, Lymphoma
Phase II
Adults
Mol. targeted/Immunotherapy/Biologics
Ibrutinib
Jagasia, Madan
National
Dana-Farber Cancer Institute, M.D. Anderson Cancer Center, Houston, Stanford University, University of Alabama/Birmingham, University of Kansas Cancer Center, Vanderbilt University
09-30-2016
Treatment
VICCBMT1651
NCT02869633

Eligibility

18 Years
BOTH
NO
Inclusion Criteria:

PRE-STEM CELL TRANSPLANT (SCT)

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 = 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 = 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 = 2 lines of therapy; prior ibrutinib therapy is permitted ** Hodgkin disease (HD) *** Disease burden: lymph node size = 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]) =
Total bilirubin =
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: 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

Use of Coumadin (warfarin) or other vitamin-K antagonists for anticoagulation; non-Coumadin anticoagulation is permitted

Known central nervous system (CNS) involvement

Active uncontrolled bacterial or invasive fungal infections

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

Planned use of post-HCT cyclophosphamide for GVHD prophylaxis

Anticipated planned donor lymphocyte infusion in the first 3 months post-SCT

T deplete HCT

Umbilical cord HCT

History of stroke or intracranial hemorrhage within 6 months of enrollment

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

Known human immunodeficiency syndrome (HIV)

Active hepatitis B or C virus

Child-Pugh class C

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

Active uncontrolled stage 3-4 acute gastrointestinal (GI) GVHD prior to administration of ibrutinib

Active uncontrolled stage 4 acute liver GVHD prior to administration of ibrutinib

Evidence of progressive disease as compared to pre-HCT (persistence of disease is permitted)

Prednisone equivalent of > 2m/kg for treatment of GVHD prior to administration of ibrutinib

Use of second line systemic therapy for treatment of acute GVHD prior to administration of ibrutinib

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

Major surgery or a wound that has not fully healed within 4 weeks of starting ibrutinib

Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon)

Requires chronic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors

Vaccinated with live, attenuated vaccines within 4 weeks of starting ibrutinib

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