Clinical trial NCT01990534: A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma
Official title: A Single-arm Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Hodgkin Lymphoma Who Are Not Suitable for Stem Cell Transplantation or Multiagent Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hodgkin Lymphoma
Keywords: Lymphoma
Hodgkin
Relapsed
Refractory
Antigens, CD30
Antibody-Drug Conjugate
Antibodies, Monoclonal
Monomethyl auristatin E
Drug Therapy
Immunotherapy
Hematologic Diseases
Additional Relevant MeSH terms:
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, T-Cell
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2013-11-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

1. 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
2. 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
3. Bidimensional measurable disease
4. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
5. 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.
6. 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.
7. Clinical laboratory values as specified in the study protocol.

Exclusion Criteria:

Participants who meet any of the following exclusion criteria are not to be enrolled in the study:

1. Previous treatment with brentuximab vedotin
2. Previously received an autologous stem cell transplantation (ASCT) or alloSCT
3. Known cerebral/meningeal disease, including signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML), or any history of PML.
4. Female participants who are lactating and breastfeeding or pregnant.
5. Known human immunodeficiency virus (HIV).
6. Known hepatitis B surface antigen positive, or known or suspected active hepatitis C infection.
7. Grade 2 or higher peripheral neuropathy.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Baseline until disease progression, death or end of study (EOS) (Up to 24 months)
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: From first documented complete or partial remission until disease progression (Up to 24 months)
measure: Progression Free Survival (PFS)
timeFrame: Baseline until disease progression, death or end of treatment (EOT), and then every 3 months up to approximately 6 years
measure: Complete Remission Rate
timeFrame: Baseline until disease progression, death or EOS (Up to approximately 6 years)
measure: Duration of Complete Remission
timeFrame: From first documented complete remission until disease progression (up to approximately 6 years)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Percentage of Participants Who Received Hematopoietic SCT
timeFrame: Baseline up to EOS (up to approximately 6 years)
measure: 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
timeFrame: From first dose through 30 days after the last dose of study medication (Up to 24 months)
measure: Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs
timeFrame: From the first dose through 30 days after the last dose of study medication (Up to 24 months)
measure: Antibody-drug Conjugate (ADC) Serum Concentrations
timeFrame: 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)
measure: Serum Concentration of Total Antibodies (Conjugated and Unconjugated)
timeFrame: 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)
measure: Monomethyl Auristatin E (MMAE) Serum Concentrations
timeFrame: 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)
measure: Number of Participants With Antitherapeutic Antibodies (ATA)
timeFrame: Day 1 of every 3-week cycle up to 16 cycles and EOT (Up to 24 months)
Other outcomes:
Locations:
city: Praha
country: Czechia
state: Prague
city: Brno
country: Czechia
city: Heidelberg
country: Germany
state: Baden Wuerttemberg
city: Koeln
country: Germany
city: Georgetown
country: Malaysia
state: Penang
city: Ampang
country: Malaysia
state: Selangor
city: Kuala Lumpur
country: Malaysia
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Warszawa
country: Poland
city: Pamplona
country: Spain
state: Navarra
city: Madrid
country: Spain
city: Bangkoknoi
country: Thailand
state: Bangkok
city: Patumwan
country: Thailand
state: Bangkok
city: Ratchathewi
country: Thailand
state: Bangkok
city: Izmir
country: Turkey
state: Bornova
city: Ankara
country: Turkey
city: Izmir
country: Turkey
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: