Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Brentuximab Vedotin and Combination Chemotherapy in Treating Older Patients With Previously Untreated Stage II-IV Hodgkin Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01476410
Recruitment Status : Active, not recruiting
First Posted : November 22, 2011
Last Update Posted : February 17, 2020
Sponsor:
Collaborators:
Robert H. Lurie Cancer Center
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Northwestern University

Tracking Information
First Submitted Date  ICMJE October 18, 2011
First Posted Date  ICMJE November 22, 2011
Last Update Posted Date February 17, 2020
Study Start Date  ICMJE November 2011
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2011)
Overall response rate after chemotherapy [ Time Frame: 2 years ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2011)
  • Overall response rate [ Time Frame: 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 progression-free survival (PFS), time to treatment failure (TTF), freedom from progression (FFP), and overall survival (OS) rates following SGN-35/AVD sequential therapy.
  • Overall response rate based on best response (CR and PR) and the tumor local control rate (CR, PR, and stable disease [SD]) [ Time Frame: 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 ]
    Estimates of response rate based on best response (CR and PR) and the tumor local control rate (CR, PR, and stable disease [SD])
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Brentuximab Vedotin and Combination Chemotherapy in Treating Older Patients With Previously Untreated Stage II-IV Hodgkin Lymphoma
Official Title  ICMJE A Phase II Trial of Sequential SGN-35 Therapy With Adriamycin, Vinblastine, and Dacarbazine (S-AVD) for Older Patients With Untreated Hodgkin Lymphoma
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.
Detailed Description

LEAD IN: Patients receive brentuximab vedotin intravenously (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.

After completion of study treatment, patients are followed up at 30 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Lymphocyte Depletion Hodgkin Lymphoma
  • Adult Lymphocyte Predominant Hodgkin Lymphoma
  • Adult Mixed Cellularity Hodgkin Lymphoma
  • Adult Nodular Sclerosis Hodgkin Lymphoma
  • Stage II Adult Hodgkin Lymphoma
  • Stage III Adult Hodgkin Lymphoma
  • Stage IV Adult Hodgkin Lymphoma
Intervention  ICMJE
  • Drug: brentuximab vedotin
    Given IV
    Other Names:
    • anti-CD30 ADC SGN-35
    • anti-CD30 antibody-drug conjugate SGN-35
    • antibody-drug conjugate SGN-35
    • SGN-35
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: vinblastine
    Given IV
    Other Names:
    • Velban
    • Velsar
    • VLB
  • Drug: dacarbazine
    Given IV
    Other Names:
    • DIC
    • DTIC
    • DTIC-Dome
  • Procedure: quality-of-life assessment
    Ancillary studies
    Other Name: quality of life assessment
  • Genetic: DNA analysis
    Optional correlative studies
  • Genetic: RNA analysis
    Optional correlative studies
  • Radiation: fludeoxyglucose F 18
    Correlative studies
    Other Names:
    • 18FDG
    • FDG
  • Procedure: positron emission tomography
    Correlative studies
    Other Names:
    • FDG-PET
    • PET
    • PET scan
    • tomography, emission computed
  • Other: laboratory biomarker analysis
    Optional correlative studies
  • Other: immunohistochemistry staining method
    Optional correlative studies
    Other Name: immunohistochemistry
  • Genetic: polymorphism analysis
    Optional correlative studies
Study Arms  ICMJE Experimental: Treatment (antibody-drug conjugate and combination chemo)

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.

Interventions:
  • Drug: brentuximab vedotin
  • Drug: doxorubicin hydrochloride
  • Drug: vinblastine
  • Drug: dacarbazine
  • Procedure: quality-of-life assessment
  • Genetic: DNA analysis
  • Genetic: RNA analysis
  • Radiation: fludeoxyglucose F 18
  • Procedure: positron emission tomography
  • Other: laboratory biomarker analysis
  • Other: immunohistochemistry staining method
  • Genetic: polymorphism analysis
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 17, 2011)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01476410
Other Study ID Numbers  ICMJE NU 11H01
NCI-2011-00684 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
STU00046908 ( Other Identifier: Northwestern University IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE
  • Robert H. Lurie Cancer Center
  • Seattle Genetics, Inc.
Investigators  ICMJE
Principal Investigator: Leo Gordon, MD Northwestern University
PRS Account Northwestern University
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP