ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02979522
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02979522
Recruitment Status : Recruiting
First Posted : December 1, 2016
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
The purpose of this study is to assess the safety, tolerability, and anti-tumor activity, as well as 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).

Condition or disease Intervention/treatment Phase
Hodgkin Disease Drug: Brentuximab vedotin Drug: Doxorubicin Drug: Vinblastine Drug: Dacarbazine Phase 1 Phase 2

Detailed Description:

The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat pediatric participants who have advanced stage, newly diagnosed, classical CD30+ HL. This study will assess the safety, tolerability, and anti-tumor activity, as well as recommended dose of brentuximab vedotin in combination with a multiagent chemotherapy regimen that is based on a current standard of care (SOC) first-line treatment regimen for newly diagnosed HL.

The study will enroll approximately 55 evaluable participants. The study will be conducted in 2 phases, Phase 1 and Phase 2. Phase 1 study will enroll up to 12 participants to determine the recommended dose. Once the recommended dose is identified additional participants will be enrolled into phase 2 so that the total number of evaluable participants will be approximately 55, including participants treated at recommended dose in Phase 1. Participants will be enrolled in the following 2 dose Cohorts:

• Brentuximab vedotin 48 mg/m^2 or 36 mg/m^2 in combination with doxorubicin, vinblastine, and dacarbazine.

Phase 1 has completed enrollment and Phase 2 is now open for enrollment.

This multi-center trial will be conducted in United States (US), Italy, Brazil, Japan, Taiwan, Singapore, and Hong Kong. The overall time to participate in this study is approximately 55 months, including the follow-up period. Participants will be followed for a maximum of 30 days following the last dose of protocol therapy for a follow-up assessment and will be followed for survival until death or study closure or a maximum of 2 years after enrollment of the last participant.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study of Brentuximab Vedotin + Adriamycin, Vinblastine, and Dacarbazine in Pediatric Patients With Advanced Stage Newly Diagnosed Hodgkin Lymphoma
Actual Study Start Date : September 7, 2017
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : October 29, 2021


Arm Intervention/treatment
Experimental: Brentuximab vedotin 48 mg/m^2
Brentuximab vedotin 48 milligram per square meter (mg/m^2), intravenous infusion, once on Day 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, intravenous infusion, once on Day 1 and 15 of each 28-day cycle for up to 6 cycles. If the first 6 participants complete the dose limiting toxicity (DLT) observation period with 0 or 1 participant experiencing a DLT, 48 mg/m^2 will be established as the recommended dose for phase 2 study. If at any time more than 1 participant out of a maximum 6 DLT-evaluable participants experiences a DLT, brentuximab vedotin dose will be reduced to 36 mg/m^2. If 0 or 1 participant experiences a DLT among the 6 participants treated at 36 mg/m^2, 36 mg/m^2 will be established as recommended dose for phase 2 study. If more than 1 participant experiences a DLT in the first 6 participants treated at 36 mg/m^2, the study will be discontinued.
Drug: Brentuximab vedotin
Brentuximab vedotin infusion
Other Name: Adcetris

Drug: Doxorubicin
Doxorubicin infusion
Other Name: Adriamycin

Drug: Vinblastine
Vinblastine infusion

Drug: Dacarbazine
Dacarbazine infusion




Primary Outcome Measures :
  1. Phase 1: Determination of the Recommended Dose of Brentuximab Vedotin in Combination With doxorubicin, vinblastine, and dacarbazine in a Pediatric Population [ Time Frame: Up to 6 months ]
    The recommended dose of brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine for a pediatric population on the basis of the safety, tolerability, and preliminary pharmacokinetic (PK) and efficacy data (if available).

  2. Phase 1: Percentage of Participants who Experience Adverse Events (AEs) From the First Dose of Protocol Therapy Through 30 days After Administration of the Last Dose of Protocol Therapy [ Time Frame: Up to 7 months ]
    The percentage of participants in the safety population who experience treatment emergent adverse events (TEAEs) for up to 6 months of treatment plus 30 days following the end of study treatment.

  3. Phase 1: Percentage of Participants who Experience Serious Adverse Events (SAEs) From the First Dose of Protocol Therapy Through 30 days After Administration of the Last Dose of Protocol Therapy [ Time Frame: Up to 7 months ]
    The percentage of participants in the safety population who experience treatment-emergent SAEs for up to 6 months of treatment plus 30 days following the end of study treatment.

  4. Phase 2: Percentage of Participants who Achieve a Complete Remission (CR) per Independent Review Facility (IRF) Assessment at end of treatment (EOT) per International Working Group (IWG) Criteria [ Time Frame: Up to 7 months ]
    Percentage of participants in the response-evaluable population who achieve a complete response based on the IRF assessment at the EOT visit based on the international working group (IWG) criteria.

  5. Phase 2: Percentage of Participants Whose Disease is Positron Emission Tomography (PET) Negative After 2 Cycles of Protocol Therapy per IRF Assessment [ Time Frame: Up to 2 months ]
    Percentage of participants in the response-evaluable population whose disease is negative per PET after 2 cycles of protocol therapy per IRF assessment.

  6. Phase 2: Percentage of Participants who Achieve a Partial Remission (PR) per IRF Assessment at EOT per IWG Criteria [ Time Frame: Up to 7 months ]
    Percentage of participants in the response-evaluable population who achieve a partial response based on the IRF assessment at the EOT visit based on the IWG criteria.

  7. Phase 2: Percentage of Participants who Achieve an Overall Response (OR) per IRF Assessment at EOT per IWG Criteria [ Time Frame: Up to 7 months ]
    Percentage of participants in the response evaluable population who achieve an overall response based on the IRF assessment at the EOT visit based on the IWG criteria.

  8. Phase 2: Percentage of Participants who are able to Complete 6 Cycles of Protocol Therapy at the Recommended Dose [ Time Frame: Up to 6 months ]
    Percentage of participants in the response-evaluable population who are able to complete six 28-day cycles of treatment at the recommended dose.


Secondary Outcome Measures :
  1. Phase 1: Mean Maximum Observed Plasma Concentration (Cmax) of Brentuximab Vedotin (Serum), Total (free and conjugated) Therapeutic Antibody (TAb) (Serum), and Monomethyl Auristatin E (MMAE) (Plasma) [ Time Frame: Up to 15 days ]
    Mean maximum concentration from Day 0 to Day 15 for brentuximab vedotin and TAb in serum and MMAE in plasma based on data from the PK population.

  2. Phase 1: Mean Area Under the Plasma Concentration-Time Curve From Day 0 to Day 15 (AUC0-15) [ Time Frame: Up to 15 days ]
    Mean AUC from Day 0 to Day 15 for brentuximab vedotin and TAb in serum and MMAE in plasma based on data from the PK population.

  3. Phase 1: Median Time to Reach Cmax (Tmax) of Brentuximab Vedotin (serum), TAb (serum), and MMAE (plasma) [ Time Frame: Up to 15 days ]
    First time of occurrence of maximum (peak) concentration for a single dose of brentuximab vedotin for participants in the PK population.

  4. Phase 1: Percentage of Participants who Achieve a CR per IRF Assessment at EOT per IWG Criteria [ Time Frame: Up to 7 months ]
    Percentage of participants in the response-evaluable population who achieve a complete response based on the IRF assessment at the EOT visit based on the IWG criteria.

  5. Phase 1: Percentage of Participants who Achieve a PR per IRF Assessment at EOT per IWG Criteria [ Time Frame: Up to 7 months ]
    Percentage of participants in the response-evaluable population who achieve a partial response based on the IRF assessment at the EOT visit based on the IWG criteria.

  6. Phase 1: Percentage of Participants who Achieve an OR per IRF Assessment at EOT per IWG Criteria [ Time Frame: Up to 7 months ]
    Percentage of participants in the response-evaluable population who achieve an overall response based on the IRF assessment at the EOT visit based on the IWG criteria.

  7. Phase 1: Percentage of Participants Whose Disease is PET Negative after 2 Cycles of Protocol Therapy per IRF Assessment [ Time Frame: Up to 2 months ]
    Percentage of participants in the response evaluable population whose disease is negative per PET after 2 cycles of protocol therapy per IRF assessment.

  8. Phase 1: Percentage of Participants Whose Disease is PET Positive After 6 Cycles of Protocol Therapy per IRF Assessment [ Time Frame: Up to 6 months ]
    Percentage of participants in the response-evaluable population whose disease is positive per PET after 6 cycles of protocol therapy per IRF assessment.

  9. Phase 1: Percentage of Participants who are Antitherapeutic Antibody (ATA) Positive, Persistently Positive or Transiently Positive, and Neutralizing Antitherapeutic Antibody (nATA) Positive [ Time Frame: Up to 7 months ]
    Percentage of participants in the safety population who are ATA positive, persistently positive, or transiently positive, and nATA positive.

  10. Phase 2: Progression-free Survival (PFS) [ Time Frame: Up to 24 months ]
  11. Phase 2: Event-free Survival (EFS) [ Time Frame: Up to 24 months ]
  12. Phase 2: Overall Survival (OS) [ Time Frame: Up to 24 months ]
  13. Phase 2: Duration of Response (DOR) [ Time Frame: Up to 24 months ]
  14. Phase 2: Percentage of Participants Receiving Irradiation for HL Following Study Treatment [ Time Frame: Up to 24 months ]
    Percentage of participants receiving irradiation for HL after up to 6 months of study treatment.

  15. Phase 2: Percentage of Participants who Experience AEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [ Time Frame: Up to 7 months ]
    The percentage of participants in the safety population who experience TEAEs for up to 6 months of treatment plus 30 days following the end of study treatment.

  16. Phase 2: Percentage of Participants who Experience SAEs From the First Dose of Protocol Therapy Through 30 Days After Administration of the Last Dose of Protocol Therapy [ Time Frame: Up to 7 months ]
    The percentage of participants in the safety population who experience treatment-emergent SAEs for up to 6 months of treatment plus 30 days following the end of study treatment.

  17. Phase 2: Percentage of Participants who are ATA Positive, Persistently Positive, or Transiently Positive, and nATA Positive [ Time Frame: Up to 7 months ]
    Percentage of participants in the safety population who are ATA positive, persistently positive, or transiently positive, and nATA positive.

  18. Phase 2: Mean Cmax of Brentuximab Vedotin (Serum), TAb (Serum), and MMAE (Plasma) [ Time Frame: Up to 15 days ]
    Mean maximum concentration from Day 0 to Day 15 for brentuximab vedotin and TAb in serum and MMAE in plasma based on data from the PK population.

  19. Phase 2: Mean AUC0-15 of Brentuximab Vedotin (Serum), TAb (Serum), and MMAE (Plasma) [ Time Frame: Up to 15 days ]
    Mean AUC from Day 0 to Day 15 for brentuximab vedotin and TAb in serum and MMAE in plasma based on data from the PK population.

  20. Phase 2: Median Tmax of Brentuximab Vedotin (Serum), TAb (Serum), and MMAE (Plasma) [ Time Frame: Up to 15 days ]
    First time of occurrence of maximum (peak) concentration for a single dose of brentuximab vedotin for participants in the PK population.

  21. Phase 2: Percentage of Participants who Experience Peripheral Neuropathy, Regardless of Seriousness, From the First Dose of Protocol Therapy Through Study Closure [ Time Frame: Up to 24 months ]
    Percentage of participants who experience peripheral neuropathy, regardless of seriousness, from the first dose of protocol therapy through study closure.

  22. Phase 2: Time to Onset and Time to Resolution for all Peripheral Neuropathy Events [ Time Frame: Up to 24 months ]
    Time from first dose of protocol therapy to onset, and time from onset to resolution for all peripheral neuropathy events.

  23. Phase 2: Immune Reconstitution Over Time [ Time Frame: Up to 24 months ]
    Immune reconstitution (peripheral blood CD34+ count; enumeration of the total lymphocyte count and lymphocyte subsets; total immunoglobulin and Immunoglobulin (Ig) G, IgM, IgA levels; levels of antibodies to tetanus, hemophilus influenza type B (HiB), and polio serotypes).

  24. Phase 1: ATA Titer [ Time Frame: Up to 6 months ]
  25. Phase 2: ATA Titer [ Time Frame: Up to 6 months ]
  26. Phase 1: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [ Time Frame: Up to 24 months ]
  27. Phase 1: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [ Time Frame: Up to 24 months ]
  28. Phase 1: Percentage of Participants Achieving CR per IRF Assessment per IWG Criteria in ATA Positive and ATA Negative Participants [ Time Frame: Up to 24 months ]
  29. Phase 1: Incidence and Severity of AEs and SAEs in ATA Positive and ATA Negative Participants [ Time Frame: Up to 24 months ]
  30. Phase 2: Mean Cmax of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [ Time Frame: Up to 24 months ]
  31. Phase 2: Mean AUC 0-15 of Brentuximab Vedotin in ATA Positive and ATA Negative Participants [ Time Frame: Up to 24 months ]
  32. Phase 2: Percentage of Participants Achieving CR per IRF Assessment per IWG Criteria in ATA Positive and ATA Negative Participants [ Time Frame: Up to 24 months ]
  33. Phase 2: Incidence and Severity of AEs and SAEs in ATA Positive and ATA Negative participants [ Time Frame: Up to 24 months ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

  1. Histologically confirmed CD30+ classical HL.
  2. Advanced stage, newly diagnosed HL (Stage III and Stage IV disease).
  3. Treatment-naive HL.
  4. Have performance scores of greater than or equal to (>=) 50 for Lansky Play-performance or Karnofsky Performance Status.

Exclusion Criteria:

  1. Nodular lymphocyte predominant HL.
  2. Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML.
  3. Any sensory or motor peripheral neuropathy.
  4. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02979522


Contacts
Contact: Takeda Study Registration Call Center +1-866-835-2233 GlobalOncologyMedinfo@takeda.com

Locations
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, Ohio
Cincinnati Childrens Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Brazil
Hospital Sao Rafael S/A Recruiting
Salvador, Bahia, Brazil, 41253-190
INCA - Instituto Nacional de Cancer Recruiting
Rio de Janeiro, Rio Do Janeiro, Brazil, 20230-230
Hospital de Clinicas de Porto Alegre Recruiting
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
Hospital de Cancer de Barretos - Fundacao Pio XII Recruiting
Barretos, Sao Paulo, Brazil, 14784-400
Jardim das Americas Recruiting
Parana, Brazil, 81520-060
GRAACC - Grupo de Apoio ao Adolescente e a Crianca com Cancer Recruiting
Sao Paulo, Brazil, 04023-062
ICr - Instituto da Crianca - HCFMUSP Recruiting
Sao Paulo, Brazil, 05403-000
Hospital Santa Marcelina Recruiting
Sao Paulo, Brazil, 08270-070
Hong Kong
The Chinese University of Hong Kong Recruiting
Shatin, Hong Kong, 00000
Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi Recruiting
Bologna, Italy, 40138
Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer Recruiting
Firenze, Italy, 50139
Fondazione IRCCS Policlinico San Matteo Recruiting
Pavia, Italy, 27100
Ospedale Pediatrico Bambino Gesu,UOC Onco-ematologia Recruiting
Roma, Italy, 165
Azienda Ospedaliera Citta della Salute e della Scienza di Torino Recruiting
Torino, Italy, 10126
Japan
NHO Nagoya Medical Center Recruiting
Nagoya-shi, Aichi-Ken, Japan, 460-0001
Kyushu University Hospital Recruiting
Fukuoka-shi, Fukuoka-Ken, Japan, 812-8582
Hokuyukai Sapporo Hokuyu Hospital Recruiting
Sapporo-shi, Hokkaido, Japan, 003-0006
St. Marianna University School of Medicine Hospital Recruiting
Kawasaki-shi, Kanagawa-Ken, Japan, 216-8511
Singapore
National University Cancer Institute Singapore Recruiting
Singapore, Singapore, 119228
Taiwan
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan, 40705
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Director Clinical Science Millennium Pharmaceuticals, Inc.

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02979522     History of Changes
Other Study ID Numbers: C25004
2015-004112-38 ( EudraCT Number )
U1111-1171-0984 ( Registry Identifier: WHO )
First Posted: December 1, 2016    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug therapy, pediatric Hodgkin disease, frontline Hodgkin disease, advanced stage Hodgkin disease, pediatric lymphoma

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Liposomal doxorubicin
Vinblastine
Antibodies, Monoclonal
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators