A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma
- Registration Number
- NCT01990534
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- Brief Summary
This phase 4, single-arm, open-label, multicenter study is designed to evaluate the efficacy and safety of brentuximab vedotin as a single agent in adult participants with histologically confirmed CD30+ relapsed or refractory classical Hodgkin Lymphoma who have not received a prior stem cell transplantation (SCT) and are considered to be not suitable for SCT or multiagent chemotherapy at the time of study entry.
- Detailed Description
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat people who have relapsed or refractory Hodgkin Lymphoma. This study will look at the overall response of people who took brentuximab vedotin.
The study will enroll 60 patients. Participants received:
• Brentuximab vedotin 1.8 mg/kg
This multicenter trial is being conducted worldwide. The overall time to participate in this study is approximately 6 to 7 years. Participants will make multiple visits to the clinic, and will be contacted by telephone every 3 months for 18 months after the end of treatment (EOT) for follow-up assessment of overall survival and then every 6 months until death, study closure, or 5 years after enrollment of the last participant.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Each participant must meet all of the following inclusion criteria to be enrolled in the study:
-
Male or female participants 18 years or older, with relapsed or refractory classical Hodgkin lymphoma (HL), who have previously received at least 1 prior systemic chemotherapeutic regimen
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Not suitable for stem cell transplantation (SCT) or multiagent chemotherapy, according to 1 of the following criteria:
- Disease progression within 90 days of the earliest date of complete remission (CR) or complete remission unconfirmed (CRu) after the end of treatment with multiagent chemotherapeutic regimens and/or radiotherapy
- Progressive disease during frontline multiagent chemotherapy
- Disease relapse after treatment with at least 2 chemotherapeutic regimens, including any salvage treatments
-
Bidimensional measurable disease
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An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
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Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception at the same time, or agree to practice true abstinence.
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Male participants who agree to practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug or agree to practice true abstinence.
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Clinical laboratory values as specified in the study protocol.
Participants who meet any of the following exclusion criteria are not to be enrolled in the study:
- Previous treatment with brentuximab vedotin
- Previously received an autologous stem cell transplantation (ASCT) or alloSCT
- Known cerebral/meningeal disease, including signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML), or any history of PML.
- Female participants who are lactating and breastfeeding or pregnant.
- Known human immunodeficiency virus (HIV).
- Known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection.
- Grade 2 or higher peripheral neuropathy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Brentuximab Vedotin 1.8 mg/kg Brentuximab Vedotin Brentuximab vedotin 1.8 mg/kg, 30-minute intravenous (IV) infusion, Day 1 in every 3-week cycle, until there is evidence of disease progression or unacceptable toxicity occurs (Up to 16 cycles). The dose could be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Baseline until disease progression, death or end of study (EOS) (Up to 24 months) Objective response rate is defined as the percentage of participants with complete remission (CR) or partial remission (PR) as assessed by an independent review facility (IRF) using International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) From first documented complete or partial remission until disease progression (Up to 24 months) DOR is defined as the time in months from the date of first documentation of a CR or PR response to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites. PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir.
Progression Free Survival (PFS) Baseline until disease progression, death or end of treatment (EOT), and then every 3 months up to approximately 6 years PFS is defined as time in months from start of study treatment to first documentation of objective tumor progression per IRF assessment or up to death due to any cause, whichever occurs first.
Complete Remission Rate Baseline until disease progression, death or EOS (Up to approximately 6 years) Complete remission rate is defined as percentage of participants with CR per IRF response assessment based on IWG criteria are reported. CR is defined as the disappearance of all evidence of disease.
Duration of Complete Remission From first documented complete remission until disease progression (up to approximately 6 years) Duration of CR is defined as the time from the date of first documentation of a CR or to the date of first documentation of tumor progression or progressive disease (PD) per IRF assessment according to IWG criteria. CR is defined as the disappearance of all evidence of disease and PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir.
Overall Survival (OS) Every 3 months for 18 months after EOT, thereafter, every 6 months until the sooner of death, study closure, or 5 years after enrollment of the last participant (up to approximately 6 years) OS is the time in months from start of study treatment to date of death due to any cause.
Percentage of Participants Who Received Hematopoietic SCT Baseline up to EOS (up to approximately 6 years) Number of Participants With Adverse Events (AEs), Drug-Related AEs, Grade 3 or Higher AEs, Serious Adverse Events (SAEs), Drug-Related SAEs and Grade 3 or Higher SAEs From first dose through 30 days after the last dose of study medication (Up to 24 months) An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE a serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. AEs Grade 3 and higher are severe.
Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs From the first dose through 30 days after the last dose of study medication (Up to 24 months) Abnormal clinical laboratory values (serum chemistry and hematology) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
Antibody-drug Conjugate (ADC) Serum Concentrations Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months) Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.
Serum Concentration of Total Antibodies (Conjugated and Unconjugated) Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months) Blood samples were collected and tested for conjugated and unconjugated antibodies.
Monomethyl Auristatin E (MMAE) Serum Concentrations Cycle 1 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 2 pre-dose and 10 minutes post-dose; Cycle 3 pre-dose and 10 minutes, 24 hours and 336 hours post-dose; Cycle 4 to 16 pre-dose and 10 minutes post-dose; EOT (Up to 24 months) Blood samples were collected and tested for MMAE serum concentrations.
Number of Participants With Antitherapeutic Antibodies (ATA) Day 1 of every 3-week cycle up to 16 cycles and EOT (Up to 24 months) Blood samples were collected to assess the immunogenicity of brentuximab vedotin (ATA development) using a laboratory test. Confirmed ATA-positive response was categorized as transient (defined as 1 or 2 post-Baseline confirmed ATA-positive responses) and persistent (defined as more than 2 post-Baseline confirmed ATA positive responses) and neutralizing ATA (nATA) status. The confirmed ATA-positive samples were assessed for ATA titer and delineated into having high or low titers.