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

February 14, 2020 updated by: Northwestern University

A Phase II Trial of Sequential SGN-35 Therapy With Adriamycin, Vinblastine, and Dacarbazine (S-AVD) for Older Patients With Untreated Hodgkin Lymphoma

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.

Study Overview

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

Interventional

Enrollment (Actual)

48

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Stanford, California, United States, 94305
        • Stanford University Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Chicago, Illinois, United States, 60611
        • NorthwesternU
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7835
        • University of Nebraska Medical Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan- Kettering Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

Ancillary studies
Other Names:
  • quality of life assessment
Correlative studies
Other Names:
  • 18FDG
  • FDG
Correlative studies
Other Names:
  • PET
  • FDG-PET
  • PET scan
  • tomography, emission computed
Given IV
Other Names:
  • ADM
  • Adriamycin PFS
  • Adriamycin RDF
  • ADR
  • Adria
Optional correlative studies
Optional correlative studies
Other Names:
  • immunohistochemistry
Given IV
Other Names:
  • DIC
  • DTIC
  • DTIC-Dome
Given IV
Other Names:
  • SGN-35
  • anti-CD30 ADC SGN-35
  • anti-CD30 antibody-drug conjugate SGN-35
  • antibody-drug conjugate SGN-35
Given IV
Other Names:
  • Velban
  • Velsar
  • VLB
Optional correlative studies
Optional correlative studies
Optional correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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])
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])
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Leo Gordon, MD, Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2011

Primary Completion (Anticipated)

May 1, 2021

Study Completion (Anticipated)

May 1, 2021

Study Registration Dates

First Submitted

October 18, 2011

First Submitted That Met QC Criteria

November 17, 2011

First Posted (Estimate)

November 22, 2011

Study Record Updates

Last Update Posted (Actual)

February 17, 2020

Last Update Submitted That Met QC Criteria

February 14, 2020

Last Verified

February 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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