Clinical trial NCT02109224 (phase 1, status: terminated)
Conditions: adult b acute lymphoblastic leukemia, chronic lymphocytic leukemia, cutaneous b-cell non-hodgkin lymphoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, hiv infection, intraocular lymphoma, multicentric angiofollicular lymphoid hyperplasia, nodal marginal zone lymphoma, recurrent adult acute lymphoblastic leukemia, recurrent adult burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade iii lymphomatoid granulomatosis, recurrent adult immunoblastic lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, refractory plasma cell myeloma, small intestinal lymphoma, splenic marginal zone lymphoma, testicular lymphoma, waldenstrom macroglobulinemia
ICD codes: C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53, C91.11, C91.12, C91.10, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, Z21, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, M26.01, M26.03, K38.0, M26.71, M26.72, N85.00, N85.01, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, A87.2, K52.832, D72.111, C91.11, C91.12, C91.10, D46.4, D46.1, D46.A, D46.0, D46.20, D46.21, D46.22, D46.4, D46.1, D46.A, D46.0, D46.20, D46.21, D46.22, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, C88.0
Drugs: ibrutinib
SMILES: NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1
Reason stopped: 
    inadequate accrual rate
  
Eligibility criteria:

        Inclusion Criteria:

          -  Known HIV infection and histologically confirmed B-cell non-Hodgkin lymphoma or B-cell
             lymphoproliferative disease as follows, as defined by the World Health Organization
             classification:

               -  Active B-cell non-Hodgkin lymphoma (cluster of differentiation [CD]20 positive or
                  negative), chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma
                  (SLL), or multiple myeloma that has relapsed, progressed, or been refractory to
                  at least one regimen

               -  Note: Patients with CLL, SLL, or mantle cell lymphoma (MCL) may only be enrolled
                  in Stratum C

          -  At least 14 days between ibrutinib initiation and last cancer therapy; any number of
             prior cancer therapies is permitted; patients otherwise fit for blood or marrow
             transplantation (BMT) should receive second-line chemotherapy before considering
             enrollment

          -  Serologic documentation of HIV infection at any time prior to study entry, as
             evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive Western
             blot, or any other federally approved licensed HIV test; alternatively, this
             documentation may include a record that another physician has documented that the
             participant has HIV infection based on prior ELISA and Western blot, or other approved
             diagnostic tests

          -  Participants must be on a stable antiretroviral regimen per current International
             Acquired Immunodeficiency Syndrome (AIDS) Society guidelines as follows, with no
             intention of changing the regimen within 8 weeks after ibrutinib initiation:

               -  Choice of regimen: The specific antiretroviral agents are at physician
                  discretion, and the use of investigational agents currently available on an
                  expanded-access basis is allowed; use of experimental antiretroviral agents or
                  those containing zidovudine (including Combivir and Trizivir) is prohibited

               -  Patients with mantle cell lymphoma, CLL, or SLL must be on non-cytochrome P450,
                  family 3, subfamily A, polypeptide 4 (CYPA3A4) modulating antiretroviral agents
                  (Stratum C) to be eligible for this study

               -  Patients may be switched to non-conflicting regimens in order to participate

               -  Stability of regimen: With the exception of patients on zidovudine-based ART, any
                  changes in antiretroviral regimen must be made at least 4 weeks prior to
                  ibrutinib initiation; patients taking zidovudine-based ART must change to a
                  non-zidovudine-based regimen at least 2 weeks prior to ibrutinib initiation;
                  changes to ART therapy during the study may be made if medically necessary (e.g.
                  toxicity, treatment failure)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Karnofsky >=
             60%)

          -  Life expectancy >= 2 months

          -  Absolute CD4+ lymphocyte count: >= 75 cells/uL

          -  Absolute neutrophil count >= 750 cells/uL

          -  Platelets >= 50,000 cells/uL, or >= 30,000/uL if bone marrow is involved by malignancy

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x
             institutional upper limit of normal (ULN), or =< 5.0 x ULN if attributable to
             malignancy

          -  Total bilirubin =< 2.0 x ULN, unless elevated bilirubin is attributable to Gilbert's
             syndrome or to HIV medications (e.g., indinavir, tenofovir, atazanavir)

          -  Creatinine clearance (CrCl) >= 40 mL/min (modified Cockcroft-Gault)

          -  All subjects must be screened for hepatitis B and C infection; subjects must either
             have no history of hepatitis B or C, or must meet the following criteria in order to e
             eligible:

               -  Hepatitis B: Subjects infected with hepatitis B must receive anti-hepatitis B
                  therapy; per Infectious Diseases Society of America (IDSA) and American
                  Association for the Study of Liver Diseases (AASLD) guidelines, subjects that
                  show no immunity, defined by the lack of hepatitis B surface antibody, and show
                  evidence of chronic infection (i.e. hepatitis B surface antigen positive
                  [HBsAg+], hepatitis B core antibody positive [HB core AB +], hepatitis B surface
                  antibody negative [HBsAB-]) must be on anti-hepatitis B therapy throughout the
                  study in order to be eligible; the exact hepatitis B therapy is at the discretion
                  of the infection disease specialist or investigator; all patients diagnosed with
                  hepatitis B must also meet the liver function test criteria listed above and have
                  no evidence of cirrhosis; however, all patients who present with acute hepatitis
                  B, or who show normal transaminases but are HBsAg+ and immunoglobulin M positive
                  (IgM+) for hepatitis B core antigen, are ineligible

               -  Hepatitis C: Subjects, who are hepatitis C antibody positive, with or without a
                  positive hepatitis C ribonucleic acid (RNA) level, must meet the liver function
                  test criteria listed above and have no evidence of cirrhosis; patients diagnosed
                  with hepatitis C less than 6 months before enrollment will be considered to have
                  acute hepatitis C and will be ineligible unless the hepatitis C viral load is
                  undetectable

          -  Must in the opinion of the investigator be capable of complying with this protocol

          -  Patients may not begin protocol therapy within 7 days of major surgery or within 3
             days of minor surgery

          -  Willingness of sexually active subjects to use adequate contraception; both men and
             women of child-bearing potential treated or enrolled on this study must agree to use
             adequate contraception (hormonal or barrier method of birth control; abstinence)
             before study entry, for the duration of study participation, and 4 months after
             completion of ibrutinib; men who only have sex with other men do not need to use
             contraception specifically for this study; (should a woman become pregnant or suspect
             she is pregnant while she or her partner is participating in this study, she should
             inform her treating physician immediately)

          -  Ability to understand and willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Prior exposure to ibrutinib

          -  Receipt of any investigational agents within 14 days before the first dose of
             ibrutinib

          -  Failure to recover to baseline or Common Terminology Criteria for Adverse Events
             (CTCAE) =< grade 2 from clinically significant toxicities due to prior cancer
             therapies or to any investigational agents

          -  Active central nervous system involvement by malignancy; central nervous system
             disease that has been treated into remission is permitted; a chart note of the
             clinician's impression of lack of central nervous system (CNS) involvement is
             acceptable

          -  Patients who require concomitant treatment with CYP3A4/5 strong inhibitors or inducers
             OTHER than antiretroviral therapies for HIV

               -  As part of the enrollment/informed consent procedures, the patient will be
                  counseled on the risk of interactions with other agents, and what to do if new
                  medications need to be prescribed or if the patient is considering a new
                  over-the-counter product

               -  A prednisone equivalent of < 20 mg daily is permitted in patients requiring
                  chronic use; larger doses must be discontinued >= 7 days prior to ibrutinib
                  initiation and are prohibited during study treatment

          -  Anticoagulation with warfarin or equivalent vitamin K antagonists within 28 days prior
             to starting ibrutinib and throughout the study

          -  Significant or uncontrolled intercurrent condition including, but not limited to:

               -  Infection other than HIV, hepatitis B, or hepatitis C that is symptomatic or
                  requires systemic treatment

               -  Opportunistic infection within 60 days prior to enrollment

               -  Currently active clinically significant cardiovascular disease such as
                  uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac
                  disease as defined by the New York Heart Association Functional Classification,
                  or history of myocardial infection within 6 months prior to enrollment

               -  History of stroke or intracranial hemorrhage within 6 months prior to enrollment

               -  History of class B or class C cirrhosis, per the modified Child-Pugh
                  classification

               -  Psychiatric illness that would limit compliance

          -  Inability to swallow capsules whole, or disease significantly affecting
             gastrointestinal function and/or inhibiting small intestine absorption, such as
             malabsorption syndrome, small bowel resection, or poorly controlled inflammatory bowel
             disease affecting the small intestine

          -  History of prior malignancy, with the exception of the following:

               -  Malignancy treated with curative intent and with no evidence of active disease
                  present for more than 3 years prior to screening and felt to be at low risk for
                  recurrence by treating physician

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

               -  Adequately treated cervical carcinoma in situ without current evidence of disease

               -  Skin-limited Kaposi sarcoma that has not required systemic treatment within 6
                  months prior to study enrollment

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ibrutinib

          -  Pregnancy or breastfeeding; a pregnancy test must be performed within 7 days prior to
             ibrutinib initiation in women of childbearing potential; pregnant women are excluded;
             breastfeeding must be discontinued