A Pilot Trial of AVD and Brentuximab Vedotin (SGN-35) in the Treatment of Stage II-IV HIV-Associated Hodgkin Lymphoma
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 for patients with
HIV-associated stage II-IV Hodgkin lymphoma when treated using brentuximab vedotin plus the
AVD chemotherapy regimen. (Phase II)
I. To evaluate the toxicity of AVD and brentuximab vedotin with highly active antiretroviral
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 CD4 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 progression-free survival (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 cycle 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
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 serum of study patients and to correlate these levels during therapy with
disease response and OS.(Phase II) XIII. To identify cytokines in the serum of patients
during therapy that can be used as tumor and prognostic markers.(Phase II)
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1 and 15.
Patients also receive doxorubicin hydrochloride IV, vinblastine sulfate IV, and dacarbazine
IV on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of
disease progression or unacceptable toxicity.
Patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximal tolerated doses of brentuximab vedotin when combined with the AVD chemotherapy regimen in HIV patients with advanced stage Hodgkin lymphoma (Phase I)
AIDS Associated Malignancies Clinical Trials Consortium
United States: Food and Drug Administration
|Pennsylvania Oncology Hematology Associates||Philadelphia, Pennsylvania 19107|