Study of Brentuximab Vedotin (SGN-35) in Pediatric Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01492088
First received: December 12, 2011
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

This is a phase 1/2, open-label, single-agent, multi-center, dose-escalation study of brentuximab vedotin in pediatric patients with relapsed or refractory systemic anaplastic large-cell lymphoma or Hodgkin lymphoma


Condition Intervention Phase
Hodgkin Lymphoma
Anaplastic Large-cell Lymphoma
Drug: brentuximab vedotin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Brentuximab Vedotin in Pediatric Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Number of Adverse events, serious adverse events, assessments of clinical and laboratory values, and vital sign measurements (phase 1) [ Time Frame: From the time informed consent is signed through 30 days after the last dose of study drug, approximately 12 months ] [ Designated as safety issue: Yes ]
    To assess the safety profile and determine the pediatric maximum tolerated dose and/or recommended phase 2 dose of brentuximab vedotin

  • Plasma concentrations of brentuximab vedotin, total therapeutic antibody, and monomethyl auristatin E (MMAE) (phase 1) [ Time Frame: All (21 day) Cycles: Day 1; Cycle 1: Days 2, 3, 5, 14; Cycle 2: Days 2 (phase 1 only), 3, 5; Cycle 8: Days 2, 3, 5, 14 ] [ Designated as safety issue: No ]
    Pharmacokinetics of brentuximab vedotin

  • Overall response rate (CR, PR) as determined by an IRF using PET, CT, MRI and, clinical assessment according to IWG revised response criteria (phase 2) [ Time Frame: PET: At Screening, Cycles 2 and 7. No additional scans needed after Cycle 7 unless clinically indicated. CT scans and MRI: Screening, Cycle 2, 4, 7, 10, 13, 16 and end of treatment and every 12 weeks thereafter for 12 months ] [ Designated as safety issue: No ]
    Complete response + partial response


Secondary Outcome Measures:
  • Anti-therapeutic antibody (ATA) titer and neutralizing ATA titer (phase 1 & phase 2) [ Time Frame: At screening, predose Day 1 at Cycle 2 and Cycle 4, and at end of treatment ] [ Designated as safety issue: No ]
    Immunogenicity of brentuximab vedotin

  • Overall response rate (CR, PR) as determined by an IRF using PET, CT, MRI and, clinical assessment according to IWG revised response criteria (phase 1) [ Time Frame: PET: At Screening, Cycles 2 and 7. No additional scans needed after Cycle 7 unless clinically indicated. CT scans and MRI: Screening, Cycle 2, 4, 7, 10, 13, 16 and end of treatment and every 12 weeks therafter for 12 months ] [ Designated as safety issue: No ]
    Complete response + partial response

  • Time to progression (phase 1 & phase 2) [ Time Frame: From the first dose of study treatment to the date of first documented progressive disease ] [ Designated as safety issue: No ]
  • Time to response (phase 1 & phase 2) [ Time Frame: From the first dose of study treatment to the date of first documentation of a complete or partial response ] [ Designated as safety issue: No ]
  • Duration of response (phase 1 & phase 2) [ Time Frame: From the date of first documentation of a response to the date of progressive disease ] [ Designated as safety issue: No ]
  • Event-free survival (phase 1 & phase 2) [ Time Frame: From first dose until treatment failure ] [ Designated as safety issue: No ]
  • Progression-free survival (phase 1 & phase 2) [ Time Frame: From the first dose of study treatment to disease progression or death ] [ Designated as safety issue: No ]
  • Overall survival (phase1 and phase 2) [ Time Frame: From the first dose of study treatment to date of death ] [ Designated as safety issue: No ]
  • Number of Adverse events, serious adverse events, assessments of clinical and laboratory values, and vital sign measurements (phase 2) [ Time Frame: From the time informed consent is signed through 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]
  • Plasma concentrations of brentuximab vedotin, total therapeutic antibody, and monomethyl auristatin E (MMAE) (phase 2) [ Time Frame: All Cycles: Day 1; Cycle 1: Days 2, 3, 5, 14; Cycle 2: Days 3, 5; Cycle 8: Days 2, 3, 5, 14 ] [ Designated as safety issue: No ]
    Pharmacokinetics of brentuximab vedotin


Estimated Enrollment: 42
Study Start Date: April 2012
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
brentuximab vedotin
Drug: brentuximab vedotin
Brentuximab vedotin will be administered by intravenous (IV) infusion once every 21 days. Each 21-day treatment cycle is composed of 1 day study drug treatment, followed by a monitoring period of 20 days. Patients may receive brentuximab vedotin for up to 16 cycles. Treatment with brentuximab vedotin beyond 16 cycles may be allowed for responding patients after discussion between the investigator and medical monitor. Following the final dose of brentuximab vedotin patients will be monitored for safety for a minimum of 30 days. Patients will be followed for progression-free survival (PFS) and overall survival (OS) every 12 weeks for 12 months after the end of treatment (EOT) visit. Thereafter, assessment for OS will continue every 6 months until the sooner of death or study closure or a maximum of 2 years after enrollment of the last patient.
Other Names:
  • SGN-35
  • ADCETRIS

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients aged 2 to <18 years (5 to <18 years for Hodgkin lymphoma (HL))
  • Diagnosis of systemic anaplastic large-cell lymphoma, or Hodgkin lymphoma for which standard, curative, life-prolonging, or palliative treatment does not exist or is no longer effective
  • Patients with systemic anaplastic large-cell lymphoma (sALCL) must have documented anaplastic lymphoma kinase (ALK) status and must be beyond first remission or refractory to front-line chemotherapy
  • Patients diagnosed with any relapsed or refractory CD30+ hematologic malignancy (e.g., primary mediastinal B-cell lymphoma) may be included in phase 1 of the study
  • Patients with HL must be in their second of later relapse, have failed systemic chemotherapy either as induction therapy for advanced stage disease or salvage therapy, and were ineligible for, refused, or previously received a stem cell transplant
  • Performance score ≥ 60 from Lansky Play Performance Scale if < 16 years
  • Negative pregnancy test
  • Fertile patients must use 2 effective methods of contraception prior to and through 6 months after the last dose of the study drug

Exclusion Criteria:

  • Current diagnosis of primary cutaneous ALCL (those with systemic ALCL are eligible)
  • Received an allogeneic stem cell transplant <3 months prior to the first dose of study medication, or presence of polymerase chain reaction (PCR)-detectable cytomegalovirus (CMV) in any post-allogeneic transplant patient
  • Receiving immunosuppressive therapy
  • Receiving systemic therapy for chronic graft-versus-host disease (topical therapy is allowed)
  • Previous treatment with any anti-CD30 antibody
  • Therapeutic monoclonal antibody use within the longer of 6 weeks or 5 plasma half-lives
  • Systemic cardiac disease that would, in the opinion of the investigator or medical monitor, interfere with assessment of efficacy or safety of the drug
  • History of another primary malignancy not in remission for at least 3 years (the following are exempt from the 3-year limit: nonmelanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear)
  • Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML
  • History of cirrhosis
  • Active systemic viral, bacterial, or fungal infection requiring antimicrobial, antiviral therapy or antifungal therapy within 2 weeks prior to the first dose of study drug (routine antimicrobial prophylaxis is acceptable)
  • Concurrent therapy with other anti-neoplastic or experimental agents
  • Systemic corticosteroid therapy <7 days prior to first dose of the study medication
  • Any serious underlying medical condition that, in the opinion of the investigator or medical monitor, would impair their ability to receive or tolerate the planned treatment
  • Known hypersensitivity to recombinant proteins, murine proteins, or any excipient contained in the drug formulation
  • Received nitrogen mustard agents, melphalan, or BCNU therapy within 6 weeks prior to the first study dose
  • Prior autologous hematopoietic stem cell infusion <4 weeks prior to first study dose
  • Grade 2 or greater unresolved toxicity from prior antineoplastic therapy
  • Grade 2 or greater peripheral neuropathy
  • Female patients who are both lactating and breastfeeding, or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug
  • Received local palliative radiation therapy <14 days prior to the first dose of study medication
  • Received radiation therapy to more than 25% of the bone marrow-containing spaces < 84 days prior to first dose of study medication
  • Received a strong or listed moderate inhibitor of CYP3A4 <2 weeks prior to first study dose
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  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: NCT01492088

Contacts
Contact: For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center 1-877-674-3784 medical@mlnm.com

Locations
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
United States, Missouri
Children's Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108
United States, New York
Memorial Sloan - Kettering Cancer Center Recruiting
New York, New York, United States, 10021
United States, Texas
The University of Texas, MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
France
Centre Leon Berard (CLB) Recruiting
Lyon, Cedex 8, France, 69373
Hopital des Enfants Unité d'Onco-Hematologie Pediatrique Recruiting
Bordeaux Cedex, France, 33076
Hopital D'Enfants Armand-Trousseau Recruiting
Paris Cedex 12, France
Germany
Charité Campus Virchow Klinikum Klinik für Pädiatrie m.S. Onkologie/Hämatologie Recruiting
Berlin, Germany
Klinikum der J.W. Goethe Universitaet Zentrum fuer Kinder und Jugend Medizin, Klinik II/III Recruiting
Frankfurt, Germany, 60590
Universitaetsklinikum Giessen und Marburg GmbH Standort Giessen Abt. Haematologie u. Onkologie Recruiting
Giessen, Germany, 35385
Universitätsklinikum Halle Klinik und Poliklinik für Kinder- und Jugendmedizin Recruiting
Halle, Germany
Uniklinikum Muenster Paediatrische Haematologie und Onkologie Recruiting
Muenster, Germany, 48149
Italy
Clinica di Oncoematologia Pediatrica, Azienda Ospedaliera-Universita di Padova Recruiting
Padova, Italy
Dipartimento di Onco-Ematologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù Recruiting
Rome, Italy
Netherlands
Erasmus Medisch Centrum - Sophia Children Hospital in Rotterdam Recruiting
Rotterdam, Netherlands, 3015GJ
Spain
Hospital Universitario Vall d'Hebron Recruiting
Barcelona, Spain, 08035
United Kingdom
University College London Hospitals NHS Trust Recruiting
London, United Kingdom, NW12PG
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01492088     History of Changes
Other Study ID Numbers: C25002, 2011-001240-29, U1111-1158-2613
Study First Received: December 12, 2011
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:
Pediatric
Lymphoma
Hodgkin
Anaplastic Large-cell
Relapsed
Refractory

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014