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

Not Applicable

Withdrawn

• Conditions: Hodgkin Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma
• Interventions: Drug: lopinavir; Drug: ritonavir; Genetic: polymerase chain reaction; Other: flow cytometry; Other: enzyme-linked immunosorbent assay; Other: laboratory biomarker analysis

• Registration Number: NCT01165645
• Lead Sponsor: Mayo Clinic

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.

Study Timeline

• Study First Submitted: 2010-07-14
• Study First Submitted QC: 2010-07-19
• Study First Posted: 2010-07-20
• Study Start: 2010-11
• Primary Completion: 2011-05
• Study Completion: 2011-12-14
• Status Verified: 2015-10
• Last Update Submitted: 2022-11-28
• Last Update Posted: 2022-12-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	polymerase chain reaction	Patients receive oral lopinavir and ritonavir twice daily for 28 days in the absence of disease progression or unacceptable toxicity.
Arm I	laboratory biomarker analysis	Patients receive oral lopinavir and ritonavir twice daily for 28 days in the absence of disease progression or unacceptable toxicity.
Arm I	enzyme-linked immunosorbent assay	Patients receive oral lopinavir and ritonavir twice daily for 28 days in the absence of disease progression or unacceptable toxicity.
Arm I	flow cytometry	Patients receive oral lopinavir and ritonavir twice daily for 28 days in the absence of disease progression or unacceptable toxicity.
Arm I	lopinavir	Patients receive oral lopinavir and ritonavir twice daily for 28 days in the absence of disease progression or unacceptable toxicity.
Arm I	ritonavir	Patients receive oral lopinavir and ritonavir twice daily for 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Comparison of TREC positive recent thymic emigrants, and naive CD4+ and CD8+ T cell numbers between treatment groups	90 days

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States