NCT01771107

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
41

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Mar 2013

Longer than P75 for phase_1

Geographic Reach
2 countries

28 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 16, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 18, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

March 8, 2013

Completed
8.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 15, 2021

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

March 3, 2023

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 21, 2024

Completed
Last Updated

August 15, 2025

Status Verified

August 1, 2025

Enrollment Period

8.6 years

First QC Date

January 16, 2013

Results QC Date

October 26, 2022

Last Update Submit

August 1, 2025

Conditions

Outcome Measures

Primary Outcomes (2)

  • Maximal Tolerated Dose of Brentuximab Vedotin (Phase I)

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

    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.

    2 years

Secondary Outcomes (18)

  • Frequency of Adverse Events

    Up to 5 years

  • Partial Response Rate

    2 years

  • Partial Response Rate

    5 years

  • Complete Response Rate

    2 years

  • Complete Response Rate

    5 years

  • +13 more secondary outcomes

Study Arms (1)

Treatment (brentuximab and combination chemotherapy)

EXPERIMENTAL

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.

Drug: Brentuximab VedotinDrug: DacarbazineDrug: Doxorubicin HydrochlorideOther: Pharmacological StudyDrug: Vinblastine

Interventions

Given IV

Also known as: ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN 35, SGN-35, SGN35
Treatment (brentuximab and combination chemotherapy)

Given IV

Also known as: 4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine, Dacarbazina, Dacarbazina Almirall, Dacarbazine - DTIC, Dacatic, Dakarbazin, Deticene, Detimedac, DIC, Dimethyl (triazeno) imidazolecarboxamide, Dimethyl Triazeno Imidazol Carboxamide, Dimethyl Triazeno Imidazole Carboxamide, dimethyl-triazeno-imidazole carboxamide, Dimethyl-triazeno-imidazole-carboximide, DTIC, DTIC-Dome, Fauldetic, Imidazole Carboxamide, Imidazole Carboxamide Dimethyltriazeno, WR-139007
Treatment (brentuximab and combination chemotherapy)

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex
Treatment (brentuximab and combination chemotherapy)

Correlative studies

Treatment (brentuximab and combination chemotherapy)

Given IV

Also known as: Vincaleucoblastine, VLB
Treatment (brentuximab and combination chemotherapy)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • HIV positive; documentation of HIV-1 infection by means of any one of the following:
  • Documentation of HIV diagnosis in the medical record by a licensed health care provider;
  • Documentation of receipt of antiretroviral therapy (ART) by a licensed health care provider;
  • HIV-1 RNA detection by a licensed HIV-1 RNA assay demonstrating \> 1000 RNA copies/mL;
  • Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 western blot confirmation or HIV rapid multispot antibody differentiation assay
  • NOTE: A "licensed" assay refers to a United States (US) Food and Drug Administration (FDA)-approved assay, which is required for all investigational new drug (IND) studies
  • 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, emergency radiation, 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
  • Total bilirubin must be \< 1.5 x the upper limit of normal, unless the elevation of bilirubin is thought to be secondary to Gilbert's syndrome or combined antiretroviral therapy (cART); 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 same criteria for hyperbilirubinemia should be applied; however 1 prior cycle of cyclophosphamide is permitted in attempt to make the participant eligible; patients should not be excluded from study participation unless dosing cannot be safely established
  • Female participants must have a negative pregnancy test within 1 week of enrollment and all participants must agree to use two reliable methods of contraception simultaneously if conception is possible during the study and for 6 months after stopping treatment; 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 participant will then be removed from protocol therapy; participants who father a child while participating in the study will be permitted to continue with the protocol; the participant, however, is required to notify the investigator if he fathers a child
  • +14 more criteria

You may not qualify if:

  • Patients with prior anthracycline therapy will be excluded
  • Female participants who are pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum beta (b)-human chorionic gonadotropin (b-hCG) or urine 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, or second malignancy requiring active treatment
  • Prior malignancy within 2 years before 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); participants with prior malignancies must have completed all therapy at least 2 years before enrollment with no evidence of disease since therapy completion
  • 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
  • Cirrhosis secondary to any cause will be excluded

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (28)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Center for Clinical AIDS Research and Education

Los Angeles, California, 90035, United States

Location

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Louisiana State University Health Science Center

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

Washington University - Jewish

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

Location

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Centre Hospitalier Universitaire (CHU) de Toulouse

Cedex, 31059, France

Location

Hopital Antoine Beclere

Clamart, 92140, France

Location

Henri Mondor University-Hospital Center

Créteil, 94000, France

Location

Hopital l'Archet-CHU de Nice

Nice, 06202, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Hospital Saint-Antoine

Paris, 75012, France

Location

Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69310, France

Location

Chu Purpan

Toulouse, 31059, France

Location

Related Publications (2)

  • Rubinstein PG, Moore PC, Bimali M, Lee JY, Rudek MA, Chadburn A, Ratner L, Henry DH, Cesarman E, DeMarco CE, Costagliola D, Taoufik Y, Ramos JC, Sharon E, Reid EG, Ambinder RF, Mitsuyasu R, Mounier N, Besson C, Noy A; AIDS Malignancy Consortium; Lymphoma Study Association. Brentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial. Lancet Haematol. 2023 Aug;10(8):e624-e632. doi: 10.1016/S2352-3026(23)00157-6.

  • Rubinstein PG, Moore PC, Rudek MA, Henry DH, Ramos JC, Ratner L, Reid E, Sharon E, Noy A; AIDS Malignancy Consortium (AMC). Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma. AIDS. 2018 Mar 13;32(5):605-611. doi: 10.1097/QAD.0000000000001729.

MeSH Terms

Conditions

HIV Infections

Interventions

Brentuximab VedotinDacarbazineDoxorubicinVinblastine

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

OligopeptidesPeptidesAmino Acids, Peptides, and ProteinsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulinsTriazenesOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizines

Results Point of Contact

Title
Kimberly Mosby-Griffin
Organization
Emmes Company

Study Officials

  • Paul G Rubinstein

    AIDS Malignancy Consortium

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 16, 2013

First Posted

January 18, 2013

Study Start

March 8, 2013

Primary Completion

October 15, 2021

Study Completion

March 21, 2024

Last Updated

August 15, 2025

Results First Posted

March 3, 2023

Record last verified: 2025-08

Locations