Advanced Classical Hodgkin Lymphoma MedDRA version: 20.0 Level: HLGT Classification code 10025319 Term: Lymphomas Hodgkin's disease System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: Adcetris®
Product Name: Adcetris ®
Product Code: SGN-35
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Brentuximab vedotin
CAS Number: 914088-09
Sponsors
Millennium Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients 18 years or older. 2. Treatment-naïve, HL patients with Ann Arbor Stage III or IV disease (refer to Section 15.1). 3. Histologically confirmed classical HL according to the current World Health Organisation Classification (nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted, or classical Hodgkin lymphoma, NOS [not otherwise specified]). 4. ECOG performance status = 2 (refer to Section 15.2). 5. Patients must have had bidimensional measurable disease as documented by radiographic technique (spiral CT preferred) per the International Working Group Revised Criteria for Response Assessment for Malignant Lymphoma (Cheson 2007).(25) 6. Female patients who: • Were postmenopausal for at least 1 year before the screening visit, OR • Were surgically sterile, OR • If they were of childbearing potential, agreed to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or • Agreed to practice true abstinence, when this was in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal were not acceptable methods of contraception.) Male patients, even if surgically sterilized (ie, status postvasectomy), who: • Agreed to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, OR • Agreed to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal were not acceptable methods of contraception.) 7. Voluntary written consent was required before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. 8. Suitable venous access for the study-required blood sampling, including PK sampling. 9. Clinical laboratory values as specified within 7 days before the first dose of study drug: • Absolute neutrophil count = 1,500/µL unless there is known HL marrow involvement • Platelet count = 75,000/µL unless there was known HL marrow involvement • Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 334
Exclusion criteria
Exclusion criteria: 1. Nodular lymphocyte predominant Hodgkin lymphoma 2. Female patients who were both lactating and breastfeeding or who had a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug 3. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol 4. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML 5. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications 6. Any sensory or motor peripheral neuropathy 7. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose 8. Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy (eg, immunoglobulin replacement, other monoclonal antibody therapies) within 12 weeks of first study drug dose 9. Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD 10. Known human immunodeficiency virus (HIV) positive 11. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection 12. Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and had any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type were not excluded if they had undergone complete resection. 13. Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug: • A left-ventricular ejection fraction < 50% • Myocardial infarction within 2 years of randomization • New York Heart Association (NYHA) Class III or IV heart failure (see Section 15.4). • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the modified progression-free survival (mPFS) obtained with brentuximab vedotin (ADCETRIS®) plus AVD (doxorubicin [Adriamycin], vinblastine, and dacarbazine; abbreviated A+AVD) versus that obtained with ABVD (doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine) for the frontline treatment of advanced classical Hodgkin lymphoma (HL);Secondary Objective: Overall survival rate To determine if A+AVD improves overall survival (OS) versus that obtained with ABVD;Primary end point(s): Modified progression-free survival (PFS) per independent review facility (IRF) ;Timepoint(s) of evaluation of this end point: •Screening •After Cycle 2: On C2D25 (± 1 day). This corresponds to 10 days (± 1 day) after the 4th dose (after C2D15) of study drug administration • At End of Treatment Visit, following last dose of frontline therapy (usually Cycle 6): 30 ± 7 days following last dose of frontline therapy. In addition, patients who switch therapy prior to completion of frontline therapy must have a scan performed prior to the first dose of alternative treatment. •During the follow-up period: every 3 months for 36 months and then every 6 months thereafter. The period of assessment will differ between patients. Analysis of the primary endpoint was completed in June 2017. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival ;Timepoint(s) of evaluation of this end point: • Screening • Days 1 & 15 of each treatment cycle (safety endpoints) • Day 1 of each treatment cycle and Days 8 & 15 of Cycles 1 & 3 (PK endpoints) • Day 1 of treatment cycles 1, 2 & 6 (antibodies endpoint) • After Cycle 2: On C2D25 (± 1 day). This corresponds to 10 days (± 1 day) after the 4th dose (after C2D15) of study drug administration • At End of Treatment Visit, following last dose of frontline therapy (usually Cycle 6): 30 +/- 7 days following last dose of frontline therapy. In addition, patients who switch therapy prior to completion of frontline therapy must have a scan performed prior to the first dose of alternative treatment. • During the follow-up period: every 3 months for 36 months and then every 6 months thereafter. | — |
Countries
Australia, Belgium, Brazil, Canada, China, Czech Republic, Denmark, France, Hong Kong, Hungary, Italy, Korea, Republic of, Norway, Poland, South Africa, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactDrug Information Call Centre
Millennium, Drug Information Call Centre
Outcome results
None listed