Lopinavir and Ritonavir in Improving Immune Response to Vaccines in Patients With Complete Remission Following A Bone Marrow Transplant for Hodgkin Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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Lopinavir/Ritonavir as an Immunomodulator to Enhance Vaccine Responsiveness

Conditions
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Hodgkin Lymphoma, Stage I Adult Hodgkin Lymphoma, Stage II Adult Hodgkin Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage IV Adult Hodgkin Lymphoma

Intervention / Treatment
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* Drug: lopinavir
* Drug: ritonavir
* Genetic: polymerase chain reaction
* Other: flow cytometry
* Other: enzyme-linked immunosorbent assay
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral lopinavir and ritonavir twice daily for 28 days in the absence of disease progression or unacceptable toxicity. | Drug: lopinavir<br>* Given orally<br>* Other names: ABT-378/r;Drug: ritonavir<br>* Given orally<br>* Other names: RIT;Genetic: polymerase chain reaction<br>* Correlative studies<br>* Other names: PCR;Other: flow cytometry<br>* Correlative studies<br>Other: enzyme-linked immunosorbent assay<br>* Correlative studies<br>* Other names: ELISA;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| No Intervention: Arm II<br>Patients receive no therapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of TREC positive recent thymic emigrants, and naive CD4+ and CD8+ T cell numbers between treatment groups |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of post-vaccination anti-rabies antibody titers between treatment groups |  | 90 days | 
| Comparison of post-vaccination cytokine levels, including IL1, IL2, IL4, IL6, IL7, IL8, IL10, IL12, INFgamma, TNFalpha, between treatment groups |  | 90 days | 
| Comparison of post-vaccination anti-rabies ELISPOT reaction between treatment groups |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult Hodgkin lymphoma