Clinical trial NCT01578967: Induction Chemo w/ABVD Followed by Brentuximab Vedotin Consolidation in Newly Diagnosed, Non-Bulky Stage I/II Hodgkin Lymphoma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hodgkin Lymphoma, Adult
Keywords: Hodgkin's lymphoma
Hodgkin lymphoma
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Seagen Inc.
First posted: 2012-04-17
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Eligibility 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 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

Primary outcomes:
measure: Percentage of Patients With Positron Emission Tomography (PET) Negative Disease
timeFrame: 12 months
Secondary outcomes:
measure: Number of Participant Who Achieved a Complete Response
timeFrame: 12 months
measure: Conversion Rate to Complete Response. Number of Participants Who Had a Partial Response Post ABVD Who Converted to a Complete Response.
timeFrame: 12 months
measure: 3 Year Progression Free Survival Rate
timeFrame: 3 years
measure: 3 Year Time to Progression Rate
timeFrame: 3 years
measure: Number of Adverse Events Attributed to Brentuximab Vedotin With a Grade 3 or Higher
timeFrame: 12 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Istitute, Carolinas Health Care system
state: North Carolina
city: Raleigh
country: United States
facility: Rex Cancer Center
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Thomas Shea, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Park SI, Shea TC, Olajide O, Reddy NM, Budde LE, Ghosh N, Deal AM, Noe JF, Ansell SM. ABVD followed by BV consolidation in risk-stratified patients with limited-stage Hodgkin lymphoma. Blood Adv. 2020 Jun 9;4(11):2548-2555. doi: 10.1182/bloodadvances.2020001871.