Last updated on June 2018

Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage II-IV HIV-Associated Hodgkin Lymphoma


Brief description of study

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. Monoclonal antibodies, such as brentuximab vedotin, may block cancer growth in different ways by targeting certain cells. 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.

Detailed Study Description

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 courses 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.

Clinical Study Identifier: NCT01771107

Contact Investigators or Research Sites near you

Start Over

William Wachsman

UC San Diego Moores Cancer Center
La Jolla, CA United States
  Connect »

Ronald T. Mitsuyasu

UCLA Center for Clinical AIDS Research and Education
Los Angeles, CA United States
  Connect »

Juan C. Ramos

University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, FL United States
  Connect »

Paul G. Rubinstein

John H Stroger Jr Hospital of Cook County
Chicago, IL United States
  Connect »

Thomas M. Reske

Louisiana State University Health Science Center
New Orleans, LA United States
  Connect »

Yvette L. Kasamon

Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, MD United States
  Connect »

Timothy P. Cooley

Boston Medical Center
Boston, MA United States
  Connect »

Ayad Hamdan

Beth Israel Deaconess Medical Center
Boston, MA United States
  Connect »

Paul G. Rubinstein

Siteman Cancer Center at Washington University
Saint Louis, MO United States
  Connect »

Paul G. Rubinstein

Washington University - Jewish
Saint Louis, MO United States
  Connect »

Lee Ratner

Washington University School of Medicine
Saint Louis, MO United States
  Connect »

Stefan K. Barta

Montefiore Medical Center-Einstein Campus
Bronx, NY United States
  Connect »

David H. Henry

Pennsylvania Oncology Hematology Associates
Philadelphia, PA United States
  Connect »

Stefan K. Barta

Fox Chase Cancer Center
Philadelphia, PA United States
  Connect »

David M. Aboulafia

Virginia Mason Medical Center
Seattle, WA United States
  Connect »

Manoj P. Menon

Harborview Medical Center
Seattle, WA United States
  Connect »

Manoj P. Menon

Fred Hutchinson Cancer Research Center
Seattle, WA United States
  Connect »

Pierre Delobel

Centre Hospitalier Universitaire (CHU) de Toulouse
Cedex, France
  Connect »

Francois Boue

Hopital Antoine Beclere
Clamart, France
  Connect »

Corinne Haioun

Henri Mondor University-Hospital Center
Creteil, France
  Connect »

Nicolas Mounier

Hopital l'Archet-CHU de Nice
Nice, France
  Connect »

Eric Oksenhendler

Hopital Saint Louis
Paris, France
  Connect »

Paul Coppo

Hospital Saint-Antoine
Paris, France
  Connect »

Gilles Salles

Centre Hospitalier Lyon-Sud
Pierre Benite, France
  Connect »

Pierre Delobel

Chu Purpan
Toulouse, France
  Connect »

Ariela Noy

Memorial Sloan Kettering Cancer Center
New York, NY United States
  Connect »

Scott D. Christensen

University of California Davis Comprehensive Cancer Center
Sacramento, CA United States
  Connect »