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

NCT01492088 | Completed Phase 1 Results FDA Drug

• 5 other identifiers: C250022011-001240-29U1111-1158-2613133300410A0384NL38209.078.11
• Study Type: interventional
• Target: 36
• Locations: 8 countries
• Sites: 18

Brief Summary

The purpose of this study is to assess the safety and pharmacokinetics, and determine the pediatric maximum tolerated dose and/or or recommended phase 2 dose of brentuximab vedotin.

Conditions

Relapsed or Refractory Hodgkin Lymphoma; Relapsed or Refractory Anaplastic Large-cell Lymphoma

Keywords

Pediatric; Lymphoma; Hodgkin; Anaplastic Large-cell; Relapsed; Refractory; Drug therapy

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1)

  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) 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.

  From the first dose through 30 days after the last dose of study medication (Up to 15 months)

• Number of Participants With Abnormal Clinical Laboratory Values Reported as AEs (Phase 1)

  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.

  From the first dose through 30 days after the last dose of study medication (Up to 15 months)

• Number of Participants With Clinically Significant Vital Signs Values Reported as AEs (Phase 1)

  Vital signs measurements included supine (after 3-5 minutes in this position) and standing (after 3-5 minutes in this position) measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.

  From the first dose through 30 days after the last dose of study medication (Up to 15 months)

• Antibody-drug Conjugate (ADC) Serum Concentrations (Phase 1)

  Blood samples were collected and tested for serum concentrations of brentuximab vedotin antibody-drug conjugate.

  Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

• Serum Concentration of Total Antibodies (Conjugated and Unconjugated) (Phase 1)

  Blood samples were collected and tested for conjugated and unconjugated antibodies.

  Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

• Monomethyl Auristatin E (MMAE) Plasma Concentrations (Phase 1)

  Blood samples were collected and tested for MMAE plasma concentrations.

  Cycle 1 and 8 pre-dose and 5 minutes, 24, 48, 96 and 312 hours post-dose; Cycle 2 pre-dose, 5 minutes and 24, 48 and 96 hours post-dose; Cycle 3 to 16 pre-dose and 5 minutes post-dose

• Overall Response Rate (ORR) (Phase 1 and 2)

  Overall 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.

  Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or end of treatment (EOT) (Up to 15 months)

Secondary Outcomes (14)

• Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing ATA (nATA) (Phase 1 and 2)

  Baseline up to EOT (Up to 15 months)

• Overall Response Rate (ORR) (Phase 1)

  Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)

• Time to Progression (TTP) (Phase 1 and 2)

  Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death (Up to 27 months)

• Time to Response (Phase 1 and 2)

  Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT (Up to 15 months)

• Duration of Response (DOR) (Phase 1 and 2)

  Cycles 2, 4, 7, 10, 13 and 16 (21-day cycles) until disease progression, death or EOT and then every 12 weeks for 12 months after EOT, until disease progression, or death or end of study (Up to 72 months)

Study Arms (2)

Brentuximab vedotin: Phase 1

EXPERIMENTAL

Brentuximab vedotin 1.4 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there was evidence of disease progression or unacceptable toxicity. Dose was escalated up to 1.8 mg/kg using a 3 + 3 dose escalation design to determine a maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) depending upon the dose limiting toxicity (DLT).

Drug: Brentuximab vedotin

Brentuximab vedotin: Phase 2

EXPERIMENTAL

Brentuximab vedotin 1.8 mg/kg, 30-minute IV infusion, Day 1 of every 21-day cycle, until there is evidence of disease progression or unacceptable toxicity (Up to 16 cycles). Treatment with brentuximab vedotin beyond 16 cycles was permitted at the joint discretion of the sponsor and the investigator for those participants experiencing continued clinical benefit.

Drug: Brentuximab vedotin

Interventions

Brentuximab vedotin DRUG

Brentuximab vedotin IV infusion

Also known as: SGN-35, ADCETRIS

Brentuximab vedotin: Phase 1; Brentuximab vedotin: Phase 2

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female participants aged 2 to \<18 years (5 to \<18 years for Hodgkin lymphoma \[HL\])
• Diagnosis of systemic anaplastic large-cell lymphoma (sALCL), or HL for which standard, curative, life-prolonging, or palliative treatment does not exist or is no longer effective
• Participants with sALCL must have documented anaplastic lymphoma kinase (ALK) status and must be beyond first remission or refractory to front-line chemotherapy
• Participants 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
• Participants 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 Participants must use 2 effective methods of contraception prior to and through 6 months after the last dose of the study drug

You may not qualify if:

• 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 participant
• 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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (18)

Unknown Facility

Aurora, Colorado, United States

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Kansas City, Missouri, United States

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New York, New York, United States

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Houston, Texas, United States

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Bordeaux, France

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Lyon, France

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Paris, France

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Berlin, Germany

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Frankfurt, Germany

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Giessen, Germany

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Halle, Germany

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Münster, Germany

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Padua, Italy

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Roma, Italy

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Mexico City, Mexico

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Rotterdam, Netherlands

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Barcelona, Spain

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Unknown Facility

London, United Kingdom

Location

Related Publications (3)

• Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.

  PMID: 17242396 RESULT

• Suri A, Mould DR, Song G, Kinley J, Venkatakrishnan K. Population Pharmacokinetics of Brentuximab Vedotin in Adult and Pediatric Patients With Relapsed/Refractory Hematologic Malignancies: Model-Informed Hypothesis Generation for Pediatric Dosing Regimens. J Clin Pharmacol. 2020 Dec;60(12):1585-1597. doi: 10.1002/jcph.1682. Epub 2020 Jun 28.

  PMID: 32596842 DERIVED

• Locatelli F, Mauz-Koerholz C, Neville K, Llort A, Beishuizen A, Daw S, Pillon M, Aladjidi N, Klingebiel T, Landman-Parker J, Medina-Sanson A, August K, Sachs J, Hoffman K, Kinley J, Song S, Song G, Zhang S, Suri A, Gore L. Brentuximab vedotin for paediatric relapsed or refractory Hodgkin's lymphoma and anaplastic large-cell lymphoma: a multicentre, open-label, phase 1/2 study. Lancet Haematol. 2018 Oct;5(10):e450-e461. doi: 10.1016/S2352-3026(18)30153-4.

  PMID: 30290902 DERIVED

MeSH Terms

Conditions

Recurrence; Hodgkin Disease; Lymphoma, Large-Cell, Anaplastic; Lymphoma

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2011
• First Posted: December 14, 2011
• Study Start: April 16, 2012
• Primary Completion: October 12, 2016
• Study Completion: April 12, 2018
• Last Updated: May 30, 2024
• Results First Posted: May 15, 2017

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

FR (3); GB (1); ES (1); US (4); ME (1); NL (1); DE (5); IT (2)