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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01578967
First Posted: April 17, 2012
Last Update Posted: December 1, 2017
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.
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
April 13, 2012
April 17, 2012
September 11, 2017
October 12, 2017
December 1, 2017
April 2012
October 2016   (Final data collection date for primary outcome measure)
Percentage of Patients With Positron Emission Tomography (PET) Negative Disease [ Time Frame: 12 months ]

Percentage of patients who convert to PET negative disease post consolidation. This is defined by PET with Deauville <=2.

The Deauville 5-point scoring system is a five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG Positron emission tomography:

Score 1: No uptake above the background Score 2: Uptake ≤ mediastinum Score 3: Uptake > mediastinum but ≤ liver Score 4: Uptake moderately increased compared to the liver at any site Score 5: Uptake markedly increased compared to the liver at any site Score X: New areas of uptake unlikely to be related to lymphoma

Feasibility [ Time Frame: 12 months ]
Percentage of patients who convert to PET negative disease post consolidation.
Complete list of historical versions of study NCT01578967 on ClinicalTrials.gov Archive Site
  • Number of Participant Who Achieved a Complete Response [ Time Frame: 12 months ]
    Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas. Complete Response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
  • Conversion Rate to Complete Response. Number of Participants Who Had a Partial Response Post ABVD Who Converted to a Complete Response. [ Time Frame: 12 months ]
    Conversion rate to Complete Response after brentuximab vedotin in patients with partial response at the end of ABVD therapy. Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas. Complete Response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. These nodes or masses should be selected according to all of the following: they should be clearly measurable in at least 2 perpendicular dimensions; if possible they should be from disparate regions of the body; and they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.
  • Progression Free Survival [ Time Frame: 5 years ]
    Defined as the time from ABVD treatment start until disease progression or death from any cause.
  • Time to Progression [ Time Frame: 5 years ]
    Defined as the time from ABVD treatment initiation until the time of disease progression or death due to progressive disease.
  • Number of Adverse Events Attributed to Brentuximab Vedotin With a Grade 3 or Higher [ Time Frame: 12 months ]
    Number of adverse events attributed to Brentuximab Vedotin with a grade 3 or higher. Toxicity assessed via the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4. The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.The higher the grade the more severe the adverse event.
  • Response Rate [ Time Frame: 5 years ]
    Response criteria based on the International Workshop to standardize response criteria for malignant lymphomas
  • Progression Free Survival [ Time Frame: 5 years ]
    Defined as the time from ABVD treatment start until disease progression or death from any cause.
  • Time to Progression [ Time Frame: 5 years ]
    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 ]
    Toxicity assessed via the NCI CTCAE v. 4
Exploratory Objective Whether the Cytokine Profile Changes After Treatment [ Time Frame: 12 months ]
To determine whether the cytokine profile changes after treatment, and to correlate serum levels of cytokines with the overall response after ABVD followed by brentuximab vedotin consolidation
Not Provided
 
Induction Chemo w/ABVD Followed by Brentuximab Vedotin Consolidation in Newly Diagnosed, Non-Bulky Stage I/II Hodgkin Lymphoma
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)

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 cluster of differentiation antigen 30 (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.

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 positron emission tomograph (PET) negative disease post brentuximab consolidation. We anticipate approximately 40 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.

Interventional
Not Provided
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hodgkin Lymphoma, Adult
  • 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.

ABVD followed by Brentuximab vedotin
Single arm trial
Interventions:
  • Drug: Brentuximab vedotin
  • Drug: ABVD
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
41
August 10, 2021
October 2016   (Final data collection date for primary outcome measure)

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 human chorionic gonadotropin (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 partial response (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 central nervous system (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
Sexes Eligible for Study: All
18 Years to 60 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01578967
LCCC 1115
Yes
Not Provided
Not Provided
UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
Seattle Genetics, Inc.
Principal Investigator: Thomas Shea, MD UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
October 2017

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