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Patients receive doxorubicin hydrochloride 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.

Doxorubicin Hydrochloride

Pharmacological Study

Paul G Rubinstein

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.

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

A Pilot Trial of AVD and Brentuximab Vedotin (SGN-35) in the Treatment of Stage II-IV HIV-Associated Hodgkin Lymphoma

Defined as the dose level at which =\< 1 of 6 subjects experience dose limiting toxicity.

2-year PFS is determined based on the Kaplan-Meier estimates and corresponding 95% confidence intervals based on standard errors using Greenwood's formula.

Number of Participants who had one or more adverse events

Number of participants who achieved a partial response per RECIST v1.0 criteria

Number of participants who experienced a complete response per RECIST v1.0 criteria

Number of participants who achieved a complete response per RECIST v1.0 criteria

Proportion of study participants who are alive at 2 years estimated using the Kaplan-Meier survival function

Proportion of participants who are alive at 5 years using a Kaplan-Meier estimate

Proportion of participants who are alive and progression-free at 2 years

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.

CD4 counts (absolute) at visit 4 (cycle 5)

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.

Log-rank analysis will be used to evaluate HAART status at baseline for difference in outcome in terms of overall survival and progression free survival.

Participants with mixed cellularity histologic subtype

Number of participants who experience neurotoxicity at cycle 5 (visit 4)

The Lymphoma Academic Research Organisation

National Cancer Institute (NCI)

Patients receive doxorubicin hydrochloride 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.

Brentuximab Vedotin: Given IV

Dacarbazine: Given IV

Doxorubicin Hydrochloride: Given IV

Pharmacological Study: Correlative studies

Vinblastine: Given IV

Phase I - Brentuximab 1.2 mg/kg

Phase II - Brentuximab 1.2 mg/kg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

France

Region of Enrollment

Kimberly Mosby-Griffin

Treatment (Brentuximab and Combination Chemotherapy)

Participants entered into the phase I portion of the study

Maximal Tolerated Dose of Brentuximab Vedotin (Phase I)

2-year Progression-free Survival (PFS)

Participants who were treated with brentuximab and combination chemotherapy

Frequency of Adverse Events

Partial Response Rate

Complete Response Rate

2-year Overall Survival

Overall Survival

Phase II Brentuximab 1.2 mg/kg

Event-free Survival

Participants with absolute cd4 counts at cycle 5

CD4 Counts

Participants with absolute CD8 counts at cycle 5

CD8 Counts

Viral Load

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

Prognostic Value of FDG-PET in Patient With HIV and HL With Respect to 2 Year Progression Free Survival

HAART Status

Characterization of Histologic Subtypes in HIV-HL in the HAART Era

Participants who had neurotoxicity evaluated at cycle 5

Incidence of Neurotoxicity

Patients receive doxorubicin hydrochloride 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.

Brentuximab Vedotin: Given IV

Spots Global Cancer Trial Database for ann arbor stage iiia hodgkin lymphoma