Know Cancer

forgot password

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

Phase 1/Phase 2
18 Years
Open (Enrolling)
HIV Infection, HIV-associated Hodgkin Lymphoma, Stage II Adult Hodgkin Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage IV Adult Hodgkin Lymphoma

Thank you

Trial Information

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
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 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.

Inclusion Criteria:

- HIV-1 infection, as documented by any federally approved, licensed HIV rapid test
performed in conjunction with screening (or enzyme-linked immunosorbent assay [ELISA]
test kit and confirmed by Western blot or other approved test); a measurable HIV
viral load alone is not sufficient for documentation of the diagnosis of HIV;
alternatively, this documentation may include a record that another physician has
documented that the participant has HIV infection based on prior ELISA and western
blot, or other approved diagnostic tests

- Histologic diagnosis of CD30-positive classical HL as defined by the 2008 World
Health Organization (WHO) Classification of Hematological diseases; nodular
lymphocyte predominant Hodgkin Lymphoma is not eligible

- Stage II, III or IV disease as defined by the Ann Arbor Staging System

- Participants must have previously untreated HIV-classical HL (cHL), with the
exception of up to 14 consecutive days of steroids or 1 prior cycle of
cyclophosphamide to reduce tumor burden and improve hyperbilirubinemia in the setting
of lymphoma related liver involvement

- Normal baseline cardiac ejection fraction >= 50%

- Serum creatinine of =< 1.5 mg/dL; if creatinine > 1.5 mg/dL, creatinine clearance
must be >= 60 mL/minute

- Absolute neutrophil count (ANC) >= 1000/uL

- Platelets >= 75,000/uL unless related to bone marrow involvement by HIV-cHL

- A direct bilirubin level of =< 2.0 mg/dL; if, however, the elevated bilirubin is felt
to be secondary to antiretroviral therapy, the total bilirubin must be =< 3.5 mg/dL,
provided that the direct bilirubin is normal and the aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) =< 3 x the upper limit of normal; also, if the
elevated bilirubin is thought to be secondary to cHL the patients should not be
excluded from study participation

- Female subjects must have a negative pregnancy test within 2 weeks of enrollment and
all subjects must agree to use two reliable methods of contraception simultaneously
if conception is possible during the study; should a woman subject become pregnant or
suspect she is pregnant while the subject is participating in this study, she should
inform her treating physician immediately; the patient will then be removed from
protocol therapy; subjects who father a child while participating in the study will
be permitted to continue with the protocol; the subject, however, is required to
notify the investigator if he fathers a child

- Ability to understand and the willingness to sign a written informed consent document

- Karnofsky performance status > 30% (given the aggressiveness of this disease and the
often severely debilitated nature of the patients at initial presentation)

- Measurable or non-measurable (evaluable) tumor parameter(s); non-measurable tumor
parameters will be defined as not having bi-dimensional measurements (i.e., gastric
or marrow involvement) but can be followed for response by other diagnostic tests
such as gallium, positron emission tomography (PET) imaging and/or bone marrow biopsy

- Patients already receiving erythropoietin or granulocyte colony stimulating factor
(GCSF) for treatment of HIV-related cytopenia are eligible

- CD4 count >= 50 cells/ul

- Subjects are required to be on antiretroviral regimens that are in accordance with
the current International acquired immune deficiency syndrome (AIDS) Society
guidelines concurrently with chemotherapy; the specific agents are at the discretion
of the Investigator and the use of investigational agents currently available on an
expanded access basis is allowed; use of experimental antiretroviral agents or those
containing zidovudine (including Combivir and Trizivir) or ritonavir (including
Kaletra), cobicistat or similar potent cytochrome P450 (CYP)3 inhibitors are
prohibited; in order to be eligible, patients taking zidovudine or ritonavir, or
cobicistat or other CYP3 inhibitors must change to a different regimen 7 days prior
to therapy initiation; changes to HAART during the study may be made if medically
necessary (toxicity, failure of regimen, etc.); subjects must be on HAART at least 12
weeks prior to therapy

- Patients will be required to obtain a pulmonary function test, despite the exclusion
of bleomycin from protocol regimen; the subject's diffusing capacity of the lung for
carbon monoxide (DLCO) adjusted for hemoglobin must be greater than 70% predicted to
enter the study and to continue with brentuximab vedotin

- Negative for Hepatitis B, or receiving anti-Hepatitis B therapy; all subjects will be
required to be screened for Hepatitis B; per Infectious Disease Society of America
(IDSA) and American Association for the Study of Liver Diseases (AASLD) guidelines,
those subjects that show no immunity, defined by the lack of Hepatitis B surface
antigen antibody, and shows evidence of chronic infection (i.e. HBcore+, HBsAB-) will
be required to be on anti-Hepatitis B therapy, during the study, in order to be
eligible; the therapy will be at the discretion of the infection disease specialist
or investigator

Exclusion Criteria:

- Patients with prior anthracycline therapy will be excluded

- Female subjects who are pregnant or breast-feeding; confirmation that the subject is
not pregnant must be established by a negative serum b-human chorionic gonadotropin
(b-hCG) pregnancy test result obtained during screening; pregnancy testing is not
required for post-menopausal or surgically sterilized women

- Medical illness unrelated to HL, which in the opinion of the study physician will
preclude administration of chemotherapy safely; this includes patients with
uncontrolled infection (including opportunistic), chronic renal failure, myocardial
infarction (MI) within the past 6 months, unstable angina, or cardiac arrhythmias
other than chronic atrial fibrillation

- Prior malignancy within 5 years of enrollment other than curatively treated cutaneous
basal cell or squamous cell carcinoma, carcinoma in situ of the cervix, anal
intraepithelial neoplasia, or cutaneous Kaposi's sarcoma (KS)

- Grade 2 or greater peripheral neuropathy

- Evidence of progressive multifocal leukoencephalopathy (PML) identified on the
pretreatment magnetic resonance imaging (MRI)

- Central nervous system disease

- Patients with history of John Cunningham (JC) Virus identified in the cerebrospinal
fluid (CSF) or previous history of PML will be excluded from the study

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximal tolerated doses of brentuximab vedotin when combined with the AVD chemotherapy regimen in HIV patients with advanced stage Hodgkin lymphoma (Phase I)

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Paul Rubinstein

Investigator Role:

Principal Investigator

Investigator Affiliation:

AIDS Associated Malignancies Clinical Trials Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

March 2013

Completion Date:

Related Keywords:

  • HIV Infection
  • HIV-associated Hodgkin Lymphoma
  • Stage II Adult Hodgkin Lymphoma
  • Stage III Adult Hodgkin Lymphoma
  • Stage IV Adult Hodgkin Lymphoma
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Hodgkin Disease
  • Lymphoma



Pennsylvania Oncology Hematology Associates Philadelphia, Pennsylvania  19107