lopinavir and ritonavir in improving immune response to vaccines in patients with complete remission following a bone marrow transplant for hodgkin lymphoma

Conditions: Hodgkin Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma

Summary: rationale: hiv protease inhibitors, including lopinavir/ritonavir have intrinsic anti-apoptotic properties in addition to their anti-viral effect on hiv. this anti-apoptotic effect may boost the immune system to help the body create a better immune response to vaccines. purpose: this randomized clinical trial studies giving lopinavir and ritonavir together in improving immune response to vaccines in patients with complete remission following a bone marrow transplant for hodgkin lymphoma.

primary objectives: i. compare trec positive recent thymic emigrants, and naive cd4+ and cd8+ t cell numbers between treatment groups. secondary objectives: i. compare post-vaccination anti-rabies antibody titers between treatment groups. ii. compare post-vaccination cytokine levels, including il1, il2, il4, il6, il7, il8, il10, il12, infgamma, tnfalpha, between treatment groups. iii. compare post-vaccination anti-rabies elispot reaction between treatment groups. outline: patients are randomized to 1 of 2 treatment arms. arm i: patients receive oral lopinavir and oral ritonavir twice daily for 28 days in the absence of disease progression or unacceptable toxicity. arm ii: patients receive no therapy. all patients then receive a neo-antigen rabies vaccine.

Eligibility criteria:
inclusion criteria: * adult subjects who are in complete remission at day +100 after a bone marrow transplant for hodgkins lymphoma * normal ast or alt, serum creatinine and 12-lead electrocardiogram within the previous 6 months * females of childbearing potential must have negative beta-hcg (urine or plasma) within the last month and agree to effective contraception during the course of the study * willingness and ability to give informed consent * willingness and ability to take pills twice a day for 28 days exclusion criteria: * known hiv positive * screening alt or ast greater than 3x upper limit of normal * baseline qtc greater than 500 msec * current treatment with immunosuppressive agent (systemic glucocorticoid, cyclosporine, mycophenolate, azathioprine, sirolimus, rituximab, infliximab, adalimumab) * current treatment with any of the following: cisapride, ergot derivatives, amiodarone, quinidine, terfenadine, astemizole, rifampin/rifabutin, carbamazepine, phenobarbital, sildenafil, st. john's wort, azithromycin, carbamazepine, hiv anti-virals, methadone, pimozide, phenytoin, sedative hypnotics (midazolam, triazolam), hmg-coa reductase inhibitors (lovastatin, simvastatin, atorvastatin) * active malignancy requiring chemotherapy or radiation * baseline creatinine of \> 2.0 * active infection requiring systemic anti-infective agent (excluding prophylactic antibiotics) * hypersensitivity to processed bovine gelatin, chicken protein, neomycin, amphotericin b or chlortetracycline * subject must not be on medications that interact with the metabolism of protease inhibitors

Keywords: recurrent adult hodgkin lymphoma