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

Takeda

Status and phase

Active, not recruiting

Phase 2

Phase 1

Conditions

Hodgkin Disease

Treatments

Drug: Vinblastine

Drug: Doxorubicin

Drug: Dacarbazine

Drug: Brentuximab vedotin

Study type

Interventional

Funder types

Industry

Identifiers

NCT02979522

2023-506415-18 (Other Identifier)

C25004

U1111-1171-0984 (Registry Identifier)

2015-004112-38 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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 at least 6 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 at least 55, including participants treated at recommended dose in Phase 1. Participants will be enrolled to the following initial dose cohort with an option to explore a reduced dose cohort at 36 mg/m^2 if needed:

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

This multi-center trial will be conducted in the United States, Italy, Brazil and Japan. 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 and disease status every 12 weeks for 12 months, and then every 24 weeks until death or study closure or for up to 2 years from the date of the last participant enrolled.

Enrollment

59 patients

Sex

All

Ages

5 to 17 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

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.

Exclusion criteria

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

59 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Dacarbazine

Drug: Brentuximab vedotin

Drug: Doxorubicin

Drug: Vinblastine

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

Experimental group

Description:

Treatment:

Drug: Dacarbazine

Drug: Brentuximab vedotin

Drug: Doxorubicin