This pilot phase I/II trial studies the side effects and the best dose of brentuximab vedotin when given together with combination chemotherapy and to see how well they work in treating patients with stage II-IV human immunodeficiency virus (HIV)-associated Hodgkin lymphoma. Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a chemotherapy drug called vedotin. Brentuximab attaches to CD30-positive cancer cells in a targeted way and delivers vedotin to kill them. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine sulfate, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin together with combination chemotherapy may kill more cancer cells.
PRIMARY OBJECTIVES I. To identify the maximum tolerated dose (MTD) of brentuximab vedotin when combined with the doxorubicin hydrochloride, vinblastine sulfate, and dacarbazine (AVD) chemotherapy regimen in the treatment of HIV-associated stage II-IV Hodgkin lymphoma. (Phase I) II. Establish an estimate of the two-year progression-free survival (PFS) for participants with HIV-associated stage II-IV Hodgkin lymphoma when treated using brentuximab vedotin plus the AVD chemotherapy regimen. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the toxicity of AVD and brentuximab vedotin with highly active antiretroviral therapy (HAART). II. To estimate the partial response (PR) rate, complete response (CR) rate, overall survival (OS), and event free survival (EFS) at 2 and 5 years. III. To evaluate the effect of AVD and brentuximab vedotin on cluster of differentiation (CD)4 and CD8 counts after cycle 1, 4, at the end of therapy, and every 3 months after treatment completion for one year. IV. To investigate the prognostic value of fludeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans at baseline, after cycle 2, and at treatment completion, with respect to 2-year progression free survival. V. To evaluate HAART status at baseline and to correlate this with tumor response to therapy and OS and PFS. VI. To characterize the histologic subtypes in HIV-Hodgkin lymphoma (HL) in the highly active antiretroviral therapy (HAART) era. VII. To assess the neurotoxicity of HAART in combination with AVD and brentuximab vedotin. VIII. To evaluate effect of AVD and brentuximab vedotin on viral load after cycles 1, 4, at the completion of therapy, and every 3 months after treatment completion for one year. IX. To perform pharmacokinetic and immunogenicity studies to determine drug levels during therapy. X. To perform micro ribonucleic acid (miRNA) profile analysis on the HIV-HL tumor specimens and to correlate miRNA expression with OS, PFS, tumor response to therapy, histologic subtype of HIV-HL, and HIV disease characteristics. XI. To perform tissue microarray analysis on HIV-HL tumor specimens and to correlate the markers studied with OS, PFS, and tumor response to therapy. XII. To identify Epstein-Barr virus (EBV)-associated tumor derived deoxyribonucleic acid (DNA) in the plasma of study participants and to correlate these levels during therapy with disease response and OS. (Phase II) XIII. To identify cytokines in the plasma of participants during therapy that can be used as tumor and prognostic markers. (Phase II) XIV. To assess latent and expressed HIV reservoirs before, during, and post chemotherapy. To understand how cytotoxic chemotherapeutic agents affect HIV expression. OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study. Patients receive doxorubicin hydrochloride intravenously (IV), vinblastine sulfate IV, and dacarbazine IV on days 1 and 15. Patients also receive brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
UC San Diego Moores Cancer Center
La Jolla, California, United States
UCLA Center for Clinical AIDS Research and Education
Los Angeles, California, United States
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Maximal Tolerated Dose of Brentuximab Vedotin (Phase I)
Defined as the dose level at which =\< 1 of 6 subjects experience dose limiting toxicity.
Time frame: 28 days
2-year Progression-free Survival (PFS) (Phase II)
2-year PFS is determined based on the Kaplan-Meier estimates and corresponding 95% confidence intervals based on standard errors using Greenwood's formula.
Time frame: 2 years
Frequency of Adverse Events
Number of Participants who had one or more adverse events
Time frame: Up to 5 years
Partial Response Rate
Number of participants who achieved a partial response per RECIST v1.0 criteria
Time frame: 2 years
Partial Response Rate
Number of participants who achieved a partial response per RECIST v1.0 criteria
Time frame: 5 years
Complete Response Rate
Number of participants who experienced a complete response per RECIST v1.0 criteria
Time frame: 2 years
Complete Response Rate
Number of participants who achieved a complete response per RECIST v1.0 criteria
Time frame: 5 years
2-year Overall Survival
Proportion of study participants who are alive at 2 years estimated using the Kaplan-Meier survival function
Time frame: 2 years
Overall Survival
Proportion of participants who are alive at 5 years using a Kaplan-Meier estimate
Time frame: 5 years
Event-free Survival
Proportion of participants who are alive and progression-free at 2 years
Time frame: 2 years
Event-free Survival
Binomial probabilities and their 95% confidence intervals will be used to estimate the response rates (i.e., partial response rate, complete response rate, overall response rate) and event free survival at 2 and 5 years of AVD and brentuximab vedotin for a treatment of patients with stage III/IV HIV-associated Hodgkin lymphoma.
Time frame: 5 years
CD4 Counts
CD4 counts (absolute) at visit 4 (cycle 5)
Time frame: 5 months
CD8 Counts
Absolute CD8 counts at cycle 5
Time frame: 5 months
Viral Load
HIV viral load (detectable)
Time frame: 5 months
Prognostic Value of Fludeoxyglucose F-18 (FDG)-Positron Emission Tomography (PET) in Patient With HIV and Hodgkin Lymphoma (HL) With Respect to 2 Year Progression Free Survival
Log-rank analysis will be used to investigate the prognostic value of FDG-PET scans at baseline, after 2 courses and post-therapy in patients with HIV and HL with respect to progression free survival.
Time frame: Baseline up to 2 years
Prognostic Value of FDG-PET in Patient With HIV and HL With Respect to 2 Year Progression Free Survival
Log-rank analysis will be used to investigate the prognostic value of FDG-PET scans at baseline, after 2 courses and post-therapy in patients with HIV and HL with respect to progression free survival.
Time frame: Baseline up to 2 years
HAART Status
Log-rank analysis will be used to evaluate HAART status at baseline for difference in outcome in terms of progression free survival at 2 years.
Time frame: Baseline up to 2 years
HAART Status
Log-rank analysis will be used to evaluate HAART status at baseline for difference in outcome in terms of overall survival at 2 years.
Time frame: Baseline up to 2 years
Characterization of Histologic Subtypes in HIV-HL in the HAART Era
Participants with mixed cellularity histologic subtype in HIV-HL in the HAART era
Time frame: Baseline
Incidence of Neurotoxicity
Number of participants who experience neurotoxicity at cycle 5 (visit 4)
Time frame: 5 months
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