Induction Chemo w/ABVD Followed by Brentuximab Vedotin Consolidation in Newly Diagnosed, Non-Bulky Stage I/II Hodgkin Lymphoma

This study is currently recruiting participants.
Verified February 2014 by UNC Lineberger Comprehensive Cancer Center
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01578967
First received: April 13, 2012
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

The standard chemotherapy for Hodgkin lymphoma is called ABVD which is a combination of 4 chemotherapy drugs (doxorubicin, bleomycin, vinblastine, and dacarbazine). The number of cycles of ABVD chemotherapy Hodgkin lymphoma patients receive is about 4-6 cycles. In addition to the ABVD chemotherapy, patients with Hodgkin lymphoma will routinely receive radiation therapy. The use of chemotherapy and radiation may cause long term treatment related side effects such as heart problems and other cancers. Researchers are trying to find if combining ABVD chemotherapy with new drugs and reducing the number of ABVD chemotherapy cycles given is just as effective as the standard Hodgkin treatment.

Brentuximab vedotin is approved by the United States Food and Drug administration (FDA) for the treatment of Hodgkin lymphoma that has come back (relapsed). For this research study, the use of brentuximab vedotin in newly diagnosed Hodgkin lymphoma is considered investigational. Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it. Antibodies are proteins that are part of your immune system. They can stick to and attack specific targets on cells. The antibody part of the brentuximab vedotin sticks to a target called CD30. CD30 is an important molecule on some cancer cells and some normal cells of the immune system.

The purpose of this research study is to see the effects of treatment with fewer cycles of the combination chemotherapy, ABVD, followed by the study drug brentuximab vedotin has on study participants and Hodgkins lymphoma.


Condition Intervention
Hodgkin Lymphoma, Adult
Drug: Brentuximab vedotin
Drug: ABVD

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: LCCC 1115: A Pilot Feasibility Trial of Induction Chemotherapy With ABVD Followed by Brentuximab Vedotin (SGN-35) Consolidation in Patients With Previously Untreated Non-Bulky Stage I or II Hodgkin Lymphoma (HL)

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Feasibility [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Percentage of patients who convert to PET negative disease post consolidation.


Secondary Outcome Measures:
  • Response Rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas

  • Progression Free Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Defined as the time from ABVD treatment start until disease progression or death from any cause.

  • Time to Progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Defined as the time from ABVD treatment initiation until the time of disease progression or death due to progressive disease.

  • Toxicity [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Toxicity assessed via the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4


Estimated Enrollment: 15
Study Start Date: April 2012
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
ABVD followed by Brentuximab vedotin
Single arm trial
Drug: Brentuximab vedotin
IV, 1.8mg/kg, every 3 weeks for 6 cycles.
Other Names:
  • SGN-35
  • Adcetris
Drug: ABVD

Doxorubicin - 25mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles.

Bleomycin - 10u/m2 IV, Day 1 and 15, every 28 days, 2-6 cycles Vinblastine - 6mg/m2 IV over 3-5 minutes, Day 1 and 15, every 28 days, 2-6 cycles.

Dacarbazine - 375mg/m2 IV over 30 minutes, Day 1 and 15, every 28 days, 2-6 cycles.

Other Name: ABVD

Detailed Description:

This study is designed as a single arm pilot feasibility trial using an induction of 2-6 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy followed by 6 cycles of brentuximab vedotin (SGN-35) consolidation for previously untreated patients with stage I and II non-bulky Hodgkin Lymphoma (HL).

Feasibility will be determined by the percentage of patients who have no clinical evidence of HL, and achieve PET negative disease post brentuximab consolidation. We anticipate approximately 20 patients will be eligible across participating centers (including UNC, Mayo Clinic, and the UNC Cancer Network (UNCCN)) over a 2 year period. A future phase II study evaluating progression free survival (PFS) after ABVD followed by brentuximab vedotin will be considered feasible if ≥ 13 of 15 patients enrolled in this pilot trial become PET negative after brentuximab vedotin consolidation.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously untreated stage I or II non-bulky Hodgkin lymphoma

    • No mediastinal mass >0.33 maximum intrathoracic diameter on chest x-ray (see Appendix B)
    • No adenopathy ≥7.5 cm in its largest diameter
  • Measurable disease as assessed by 2 dimensional measurement by CT (>2cm or 1.5 cm if 0.5 cm slices are used, as in spiral CT scan)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Age ≥18 years and ≤60 years of age
  • Life expectancy of at least 3 months
  • Adequate bone marrow function (without transfusion support within one week of screening) as demonstrated by:

    • Hemoglobin ≥ 8 g/dL
    • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
    • Platelet count ≥ 75,000/mm3
  • Adequate hepatic and renal function as demonstrated by:

    • Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
    • Total serum bilirubin ≤1.5 x ULN
    • Serum creatinine ≤ 2.0 mg/dL
  • Negative serum β-hCG pregnancy test within 72 hours of day 1 of treatment with ABVD in women of child-bearing potential
  • Females of childbearing potential, and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of brentuximab vedotin. Effective contraception is defined as any medically recommended method (or combination of methods) as per standard of care, including abstinence. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
  • Signed an institutional review board (IRB)-approved informed consent document for this protocol

Prior to Day 1 of brentuximab vedotin, patients must again meet the following inclusion criteria:

  • Adequate bone marrow function (without transfusion support within one week of D1 of brentuximab vedotin) as demonstrated by:

    • Hemoglobin ≥ 8 g/dL
    • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
    • Platelet count ≥ 75,000/mm3
  • Adequate hepatic and renal function as demonstrated by:

    • Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
    • Total serum bilirubin ≤1.5 x ULN
    • Serum creatinine ≤ 2.0 mg/dL
  • Achieved at least a PR (and not progressed) after ABVD therapy

Exclusion Criteria:

  • Prior therapies for treatment of HL including involved field radiation therapy or any prior treatment for any malignancy with anthracyclines.
  • Bulky disease (defined as a mass measuring > 7.5 cm or one-third the maximal diameter of the thoracic cavity)
  • Known CNS involvement
  • Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators
  • Known history of human immunodeficiency virus (HIV), hepatitis B and hepatitis C (testing is not necessary if patient does not have history of these diseases, and no risk factors for acquisition of these viruses)
  • Cardiac disease with left ventricular ejection fraction of less than 45%
  • Known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD
  • Medical or other condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective
  • Other active malignancies with the exception of:

    • Non-melanoma skin cancer
    • Cervical carcinoma in situ without evidence of disease
    • Prostatic intraepithelial neoplasia without evidence of prostate cancer
  • Pregnant or lactating women

Prior to Day 1 of brentuximab vedotin, please verify the patient does not meet the criteria below:

  • Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01578967

Contacts
Contact: Clinical Protocol Office 919-966-4432

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Stephen Ansell, MD         
United States, North Carolina
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Donna Rowe, RN    919-966-7359    donna_rowe@med.unc.edu   
Principal Investigator: Steven Park, MD         
Rex Cancer Center Recruiting
Raleigh, North Carolina, United States, 27607
Principal Investigator: Oludamilola Olajide, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37240
Principal Investigator: Nishitha Reddy, MD         
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Seattle Genetics, Inc.
Investigators
Principal Investigator: Steven Park, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01578967     History of Changes
Other Study ID Numbers: LCCC 1115
Study First Received: April 13, 2012
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Hodgkin's lymphoma
Hodgkin lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014