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A Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier:
NCT01990534
First received: November 15, 2013
Last updated: February 21, 2017
Last verified: February 2017
  Purpose
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.

Condition Intervention Phase
Hodgkin Lymphoma
Drug: Brentuximab vedotin
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Takeda:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Baseline up to Cycle 16 (3-week cycle) until disease progression, death or end of treatment (EOT) (Up to 12.2 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:
  • Duration of Response (DOR) [ Time Frame: From first documented response until disease progression (Up to 12.2 months) ]
    DOR is defined as the time in months from the date of first documentation of a CR 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 and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.

  • Progression Free Survival (PFS) [ Time Frame: Baseline up to Cycle 16 (3-week cycle) until disease progression, death or EOT, and then every 3 months up to data cut-off: 23 May 2016 (approximate median follow-up 6.9 months) ]
    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 [ Time Frame: Baseline up to Cycle 16 (3-week cycles) until disease progression, death or EOT (Up to 12.2 months) ]
    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 (CR) [ Time Frame: From first documented response until disease progression (Up to 12.2 months) ]
    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) [ Time Frame: 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 data cut-off: 23 May 2016 (approximate median follow-up 16.6 months) ]
    OS is the time in months from start of study treatment to date of death due to any cause.

  • Percentage of Participants who Received Stem Cell Transplantation (SCT) [ Time Frame: Baseline up to EOT (Up to 12.2 months) ]
  • 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 [ Time Frame: From the first dose through 30 days after the last dose of study medication (Up to 12.2 months) ]
    An Adverse Event (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 Serious Adverse Event (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 [ Time Frame: From the first dose through 30 days after the last dose of study medication (Up to 12.2 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 [ Time Frame: 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 12.2 months) ]
    Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.

  • Serum Concentration of Total Antibodies (Conjugated and Unconjugated) [ Time Frame: 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 12.2 months) ]
    Blood samples were collected and tested for conjugated and unconjugated antibodies.

  • Monomethyl Auristatin E (MMAE) Serum Concentrations [ Time Frame: 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 12.2 months) ]
    Blood samples were collected and tested for MMAE serum concentrations.

  • Number of Participants With Antitherapeutic Antibodies (ATA) [ Time Frame: Day 1 of every 3-week cycle up to 16 cycles and EOT (Up to 12.2 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.


Enrollment: 60
Study Start Date: March 2014
Estimated Study Completion Date: March 2020
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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 may be decreased or delayed or discontinued in participants who develop treatment-associated non-hematologic, hematologic toxicity or peripheral neuropathy to brentuximab vedotin.
Drug: Brentuximab vedotin
Brentuximab vedotin IV infusion
Other Names:
  • SGN-35
  • ADCETRIS

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 enrolled 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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01990534

Locations
Czech Republic
Praha, Prague, Czech Republic
Brno, Czech Republic
Germany
Heidelberg, Baden Wuerttemberg, Germany
Koeln, Germany
Malaysia
Georgetown, Penang, Malaysia
Ampang, Selangor, Malaysia
Kuala Lumpur, Malaysia
Poland
Gdansk, Poland
Krakow, Poland
Warszawa, Poland
Spain
Pamplona, Navarra, Spain
Madrid, Spain
Thailand
Bangkoknoi, Bangkok, Thailand
Patumwan, Bangkok, Thailand
Ratchathewi, Bangkok, Thailand
Turkey
Izmir, Bornova, Turkey
Ankara, Turkey
Izmir, Turkey
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01990534     History of Changes
Other Study ID Numbers: C25007  2013-000232-10  U1111-1154-2250  NMRR-13-1246-18099  REec-2014-0619 
Study First Received: November 15, 2013
Last Updated: February 21, 2017

Keywords provided by Takeda:
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

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 24, 2017