A Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Pediatric Participants With Advanced Stage Newly Diagnosed Hodgkin Lymphoma

NCT02979522 | Active Not Recruiting Phase 1 Results FDA Drug

• 4 other identifiers: C250042015-004112-38U1111-1171-09842023-506415-18-00
• Study Type: interventional
• Target: 59
• Locations: 4 countries
• Sites: 14

Brief Summary

The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as confirm the recommended dose of brentuximab vedotin (ADCETRIS) in combination with a multiagent chemotherapy regimen, doxorubicin (Adriamycin), vinblastine, and dacarbazine, in pediatric participants with advanced stage newly diagnosed classical CD30+ Hodgkin Lymphoma (HL).

Conditions

Hodgkin Disease

Keywords

Drug therapy, pediatric Hodgkin disease, frontline Hodgkin disease, advanced stage Hodgkin disease, pediatric lymphoma

Outcome Measures

Primary Outcomes (8)

• Phase 1: Recommended Dose of Brentuximab Vedotin in Combination With Doxorubicin, Vinblastine, and Dacarbazine in a Pediatric Population

  The recommended dose was determined after considering all safety data in phase 1 and assessing for dose limiting toxicities (DLTs) which are defined as the dose range at which less than or equal to (\<=) 1 of 6 evaluable participants experience DLT within the defined observation period (Cycle 1 + 28 days). This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.

  From the first dose (Cycle 1) up to Day 56 (Cycle length=28 days)

• Phase 1: Percentage of Participants Who Experienced Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy

  AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This outcome measure is planned to be assessed only for participants treated in Phase 1 arm.

  From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)

• Phase 1: Percentage of Participants Who Experienced Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy

  AE means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, Is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, Is a congenital anomaly/birth defect, Is a medically important event.

  From first dose in Cycle 1 Day 1 until 30 days after the last dose of study drug in Cycle 6 Day 15 (up to Cycle 7 Day 15) (Cycle length=28 days)

• Phase 2: Percentage of Participants Who Achieved a Complete Remission (CR) Per Independent Review Facility (IRF) Assessment Per International Working Group (IWG) Criteria at End of Treatment (EOT) Visit

  CR was defined as the disappearance of all evidence of disease as assessed by IRF as per IWG Criteria. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in the statistical analysis plan (SAP) , data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.

  At end of treatment (EOT) visit 30 days after the last dose of study drug (at Month 7)

• Phase 2: Percentage of Participants Whose Disease Was Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy Per IRF Assessment

  The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. PET negative after Cycle 2 was defined as an IRF Deauville score of (1 or 2 or 3). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.

  From first dose of study drug up to Cycle 2 Day 25 (Each Cycle length=28 days)

• Phase 2: Percentage of Participants Who Achieved a Partial Remission (PR) Per IRF Assessment Per IWG Criteria at EOT Visit

  PR was defined as regression of measurable disease and no new sites as assessed by IRF as per IWG criteria. Percentage of participants in the response-evaluable population who achieved a partial response based on the IRF assessment at the EOT visit based on the IWG criteria are reported. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.

  At EOT visit 30 days after the last dose of study drug (at Month 7)

• Phase 2: Percentage of Participants Who Achieved an Overall Response Rate (ORR) Per IRF Assessment Per IWG Criteria at EOT Visit

  Overall response rate was defined as the percentage of participants with CR or PR as assessed by IRF using IWG criteria. CR was defined as the disappearance of all evidence of disease and PR was defined as regression of measurable disease and no new diseases. The confidence interval was based on exact binomial distribution (Clopper-Pearson method). This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.

  At EOT visit 30 days after the last dose of study drug (at Month 7)

• Phase 2: Percentage of Participants Who Were Able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose

  This outcome measure was planned to be assessed for all participants treated at the recommended dose in Phase 2. As prespecified in SAP, data for Phase 2 was summarized and reported in two arms: Phase 2 and Phase 1 + Phase 2.

  From first dose of study drug up to Cycle 6 (Each Cycle length=28 days)

Secondary Outcomes (49)

• Phase 1: Mean Maximum Observed Serum Concentration (Cmax) of Brentuximab Vedotin Total Conjugated and Therapeutic Antibody (TAb)

  Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

• Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Monomethyl Auristatin E (MMAE)

  Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

• Phase 1: Mean Area Under the Serum Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of Brentuximab Vedotin and TAb

  Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

• Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) of MMAE

  Days 1 and 15 of Cycles 1 and 3 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

• Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin and TAb in Serum

  Cycle 1-6: Days 1 and 15 pre-infusion and up to 30 minutes after the end of infusion (Cycle length=28 days)

Study Arms (2)

Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD

EXPERIMENTAL

Brentuximab vedotin 48 mg/m\^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.

Drug: Brentuximab vedotin; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine

Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD

EXPERIMENTAL

Brentuximab vedotin 48 mg/m\^2 (A), intravenous infusion, once on Days 1 and 15 of each 28-day cycle approximately 1 hour after administration of doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (AVD), intravenous infusion, once on Days 1 and 15 of each 28-day cycle for up to 6 cycles.

Drug: Brentuximab vedotin; Drug: Doxorubicin; Drug: Vinblastine; Drug: Dacarbazine

Interventions

Brentuximab vedotin DRUG

Brentuximab vedotin infusion

Also known as: Adcetris

Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD; Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD

Doxorubicin DRUG

Doxorubicin infusion

Also known as: Adriamycin

Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD; Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD

Vinblastine DRUG

Vinblastine infusion

Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD; Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD

Dacarbazine DRUG

Dacarbazine infusion

Phase 1: Brentuximab Vedotin 48 mg/m^2 + AVD; Phase 2: Brentuximab Vedotin 48 mg/m^2 + AVD

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Histologically confirmed CD30+ classical HL.
• Advanced stage, newly diagnosed HL (Stage III and Stage IV disease).
• Treatment-naive HL.
• Have performance scores of greater than or equal to (\>=) 50 for Lansky Play-performance or Karnofsky Performance Status.
• Have bidimensional measurable disease as documented by radiographic technique per International Working Group (IWG) criteria.
• Have adequate blood counts, renal and liver function as defined in the protocol.

You may not qualify if:

• Nodular lymphocyte predominant HL.
• Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML.
• Any sensory or motor peripheral neuropathy.
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medications.
• Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks before the first study protocol therapy.
• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of AVD.
• Known human immunodeficiency virus positive.
• Known hepatitis B surface antigen positive or known or suspected active hepatitis C infection, as determined by hepatitis B DNA or hepatitis C RNA, respectively, in blood.
• Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Use of any strong or listed moderate cytochrome P450 (CYP) 3A4 inhibitors less than (\<) 2 weeks before the first dose of protocol therapy (please refer to the Study Manual for an example list of prohibited CYP3A4 inhibitors).
• Any of the following cardiovascular conditions or values within 6 months before the first dose of protocol therapy:
• Shortening fraction of \<27 percent (%) by echocardiogram or, if echocardiogram not feasible, ejection fraction of \<50% by radionuclide angiogram (RNA or MUGA \[multiple-gated acquisition scan\]).
• New York Heart Association Class III or IV heart failure.
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

Sponsors & Collaborators

• Takeda: lead

Study Sites (14)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Hospital Sao Rafael S/A

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Jardim das Americas

Paranã, 81520-060, Brazil

Location

INCA - Instituto Nacional de Cancer

Rio de Janeiro, 20230-230, Brazil

Location

GRAACC - Grupo de Apoio ao Adolescente e a Crianca com Cancer

São Paulo, 04023-062, Brazil

Location

ICr - Instituto da Crianca - HCFMUSP

São Paulo, 05403-000, Brazil

Location

Hospital Santa Marcelina

São Paulo, 08270-070, Brazil

Location

Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer

Florence, 50139, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Ospedale Pediatrico Bambino Gesu,UOC Onco-ematologia

Roma, 165, Italy

Location

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

NHO Nagoya Medical Center

Nagoya, Aichi-ken, 460-0001, Japan

Location

St. Marianna University School of Medicine Hospital

Kawasaki-shi, Kanagawa, 216-8511, Japan

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Brentuximab Vedotin; Doxorubicin; Vinblastine; Dacarbazine

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2016
• First Posted: December 1, 2016
• Study Start: September 6, 2017
• Primary Completion: May 5, 2020
• Study Completion (Estimated): September 24, 2029
• Last Updated: November 10, 2025
• Results First Posted: June 1, 2021

Record last verified: 2025-11

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

BR (6); IT (4); US (2); JP (2)