NCT01476410

Brief Summary

This phase II trial studies how well giving brentuximab vedotin together with combination chemotherapy works in treating older patients with previously untreated stage II-IV Hodgkin lymphoma (HL). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine (AVD), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin, doxorubicin hydrochloride, vinblastine, and dacarbazine together may kill more cancer cells.

Trial Health

43
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Enrollment
48

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Nov 2011

Longer than P75 for phase_2

Geographic Reach
1 country

7 active sites

Status
unknown

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

October 18, 2011

Completed
14 days until next milestone

Study Start

First participant enrolled

November 1, 2011

Completed
21 days until next milestone

First Posted

Study publicly available on registry

November 22, 2011

Completed
9.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2021

Completed
Last Updated

February 17, 2020

Status Verified

February 1, 2020

Enrollment Period

9.5 years

First QC Date

October 18, 2011

Last Update Submit

February 14, 2020

Conditions

Adult Lymphocyte Depletion Hodgkin LymphomaAdult Lymphocyte Predominant Hodgkin LymphomaAdult Mixed Cellularity Hodgkin LymphomaAdult Nodular Sclerosis Hodgkin LymphomaStage II Adult Hodgkin LymphomaStage III Adult Hodgkin LymphomaStage IV Adult Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

  • Overall response rate after chemotherapy

    The primary objective of this study is to assess the overall response rate among older patients with HL receiving sequential brentuximab vedotin therapy with AVD chemotherapy

    2 years

Secondary Outcomes (2)

  • Overall response rate

    Baseline, every 3 weeks during the first 2 cycles, every 2 weeks during next 6 cycles, every 4 weeks furing the last 4 cycles, and then every 3 months for up to 3 years from entering the study

  • Overall response rate based on best response (CR and PR) and the tumor local control rate (CR, PR, and stable disease [SD])

    Baseline, every 3 weeks during the first 2 cycles, every 2 weeks during next 6 cycles, every 4 weeks furing the last 4 cycles, and then every 3 months for up to 3 years from entering the study

Study Arms (1)

Treatment (antibody-drug conjugate and combination chemo)

EXPERIMENTAL

LEAD-IN: Patients receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. AVD CHEMOTHERAPY: Patients then receive doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving CR receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Drug: brentuximab vedotinDrug: doxorubicin hydrochlorideDrug: vinblastineDrug: dacarbazineProcedure: quality-of-life assessmentGenetic: DNA analysisGenetic: RNA analysisRadiation: fludeoxyglucose F 18Procedure: positron emission tomographyOther: laboratory biomarker analysisOther: immunohistochemistry staining methodGenetic: polymorphism analysis

Interventions

brentuximab vedotinDRUG

Given IV

Also known as: anti-CD30 ADC SGN-35, anti-CD30 antibody-drug conjugate SGN-35, antibody-drug conjugate SGN-35, SGN-35
Treatment (antibody-drug conjugate and combination chemo)
doxorubicin hydrochlorideDRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Treatment (antibody-drug conjugate and combination chemo)
vinblastineDRUG

Given IV

Also known as: Velban, Velsar, VLB
Treatment (antibody-drug conjugate and combination chemo)
dacarbazineDRUG

Given IV

Also known as: DIC, DTIC, DTIC-Dome
Treatment (antibody-drug conjugate and combination chemo)
quality-of-life assessmentPROCEDURE

Ancillary studies

Also known as: quality of life assessment
Treatment (antibody-drug conjugate and combination chemo)
DNA analysisGENETIC

Optional correlative studies

Treatment (antibody-drug conjugate and combination chemo)
RNA analysisGENETIC

Optional correlative studies

Treatment (antibody-drug conjugate and combination chemo)
fludeoxyglucose F 18RADIATION

Correlative studies

Also known as: 18FDG, FDG
Treatment (antibody-drug conjugate and combination chemo)
positron emission tomographyPROCEDURE

Correlative studies

Also known as: FDG-PET, PET, PET scan, tomography, emission computed
Treatment (antibody-drug conjugate and combination chemo)
laboratory biomarker analysisOTHER

Optional correlative studies

Treatment (antibody-drug conjugate and combination chemo)
immunohistochemistry staining methodOTHER

Optional correlative studies

Also known as: immunohistochemistry
Treatment (antibody-drug conjugate and combination chemo)
polymorphism analysisGENETIC

Optional correlative studies

Treatment (antibody-drug conjugate and combination chemo)

Eligibility Criteria

Age60 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Previously untreated classical Hodgkin lymphoma (i.e., nodular sclerosis, mixed cellularity, lymphocyte depleted, lymphocyte-rich, and not otherwise specified \[NOS\]); nodular lymphocyte predominant Hodgkin lymphoma is not eligible
  • Stage II, III, and IV disease by Ann Arbor classification
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Patients must have bi-dimensional measurable disease documented in the lymphoma baseline tumor assessment form within 30 days prior to registration (at least 1.5 cm); patients with non-measurable disease in addition to measurable disease must have been assessed within 60 days prior to registration
  • Patients must have a bone marrow biopsy (bilateral preferred, unilateral acceptable) within 60 days prior to registration
  • Patients must have a multi gated acquisition scan (MUGA) or echocardiogram within 60 days prior to study registration and the ejection fraction must be \>= 45%
  • Absolute neutrophil count (ANC) \> 1000/mm\^3
  • Platelet count \> 75,000/mm\^3
  • Creatinine \< 2.5 mg/dl
  • Bilirubin \< 3.0 mg/dl
  • Patients with documented marrow involvement by lymphoma at the time of registration are not required to meet the above hematologic parameters
  • Patients must not have received prior chemotherapy or radiation therapy for the treatment of Hodgkin lymphoma
  • Both females and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
  • Patients must sign the informed consent form before registration

You may not qualify if:

  • Previous treatment with brentuximab vedotin or any other prior anti-CD30-based antibody therapy
  • History of another primary malignancy that has not been in remission for at least 3 years; (the following are exempt from the 3-year limit: early stage \[stage I or II\] breast cancer treated with surgery and radiation +/- hormones \[without adjuvant chemotherapy\], non-melanoma skin cancer, fully excised melanoma in situ \[stage 0\], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou test \[PAP smear\])
  • Known cerebral/meningeal disease
  • Any active systemic viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 1 week prior to first dose
  • Patients with hepatitis B surface antigen (HBsAg) positive hepatitis B virus (HBV) infection; patients with prior history of hepatitis B infection, but immune, with only Immunoglobulin G (IgG) hepatitis core antibody + (HBcAb +) must receive anti-viral prophylaxis (e.g., lamivudine 100mg orally \[po\] daily) for at least 1 week prior to cycle 1 and throughout induction and continuation therapy and for at least 6 months after the last brentuximab vedotin dose; in addition, consultation with a hepatologist is recommended
  • Patients with a known hypersensitivity to any excipient contained in the drug formulation
  • Patients with dementia or an altered mental state that would preclude the understanding and rendering of informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

NorthwesternU

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7835, United States

Location

Memorial Sloan- Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • Evens AM, Advani RH, Helenowski IB, Fanale M, Smith SM, Jovanovic BD, Bociek GR, Klein AK, Winter JN, Gordon LI, Hamlin PA. Multicenter Phase II Study of Sequential Brentuximab Vedotin and Doxorubicin, Vinblastine, and Dacarbazine Chemotherapy for Older Patients With Untreated Classical Hodgkin Lymphoma. J Clin Oncol. 2018 Oct 20;36(30):3015-3022. doi: 10.1200/JCO.2018.79.0139. Epub 2018 Sep 4.

    PMID: 30179569DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Brentuximab VedotinDoxorubicinVinblastineDacarbazineFluorodeoxyglucose F18Magnetic Resonance Spectroscopy2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazoleImmunohistochemistryAmplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

OligopeptidesPeptidesAmino Acids, Peptides, and ProteinsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulinsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesTriazenesImidazolesAzolesHeterocyclic Compounds, 1-RingDeoxyglucoseDeoxy SugarsSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative TechniquesHistocytochemistryCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisHistological TechniquesImmunologic TechniquesDNA FingerprintingGenetic TechniquesPolymerase Chain ReactionNucleic Acid Amplification Techniques

Study Officials

  • Leo Gordon, MD

    Northwestern University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 18, 2011

First Posted

November 22, 2011

Study Start

November 1, 2011

Primary Completion

May 1, 2021

Study Completion

May 1, 2021

Last Updated

February 17, 2020

Record last verified: 2020-02

Locations

US(7)