Clinical trial NCT01165645: Lopinavir and Ritonavir in Improving Immune Response to Vaccines in Patients With Complete Remission Following A Bone Marrow Transplant for Hodgkin Lymphoma
Official title: Lopinavir/Ritonavir as an Immunomodulator to Enhance Vaccine Responsiveness
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Hodgkin Lymphoma
Stage I Adult Hodgkin Lymphoma
Stage II Adult Hodgkin Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage IV Adult Hodgkin Lymphoma
Keywords: recurrent adult Hodgkin lymphoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2010-07-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
measure: Comparison of TREC positive recent thymic emigrants, and naive CD4+ and CD8+ T cell numbers between treatment groups
timeFrame: 90 days
Secondary outcomes:
measure: Comparison of post-vaccination anti-rabies antibody titers between treatment groups
timeFrame: 90 days
measure: Comparison of post-vaccination cytokine levels, including IL1, IL2, IL4, IL6, IL7, IL8, IL10, IL12, INFgamma, TNFalpha, between treatment groups
timeFrame: 90 days
measure: Comparison of post-vaccination anti-rabies ELISPOT reaction between treatment groups
timeFrame: 90 days
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Stacey Rizza, M.D.
role: STUDY_CHAIR
References: