Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma

St. Jude Children's Research Hospital

Status and phase

Active, not recruiting

Phase 2

Conditions

Stage III Childhood Hodgkin Lymphoma

Stage II Childhood Hodgkin Lymphoma

Stage IV Childhood Hodgkin Lymphoma

Treatments

Other: quality of life assessment

Drug: Dacarbazine(R)

Drug: etoposide

Drug: cyclophosphamide

Radiation: radiation therapy

Drug: prednisone

Drug: brentuximab vedotin

Drug: filgrastim

Drug: doxorubicin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01920932

NCI-2013-01123 (Registry Identifier)

HLHR13

Details and patient eligibility

About

This pilot phase II trial studies how well giving brentuximab vedotin, combination chemotherapy, and radiation therapy works in treating younger patients with stage IIB, IIIB or IV Hodgkin lymphoma. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Drugs used in chemotherapy, such as etoposide, prednisone, doxorubicin hydrochloride, cyclophosphamide, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving brentuximab vedotin with combination chemotherapy may kill more cancer cells and reduce the need for radiation therapy.

Full description

PRIMARY OBJECTIVES:

To evaluate the safety of brentuximab vedotin, etoposide, prednisone and doxorubicin hydrochloride (AEPA)/cyclophosphamide, brentuximab vedotin, prednisone and dacarbazine (CAPDac), as well as the efficacy (early complete response) after 2 cycles of AEPA chemotherapy in high risk patients with Hodgkin lymphoma (HL).
To compare the event-free survival in high risk HL patients treated with AEPA/CAPDac to the historical control unfavorable risk 2 arm (UR2) of the St. Jude HOD99 study.

SECONDARY OBJECTIVES:

To estimate the number of patients with adequate response according to the definitions in the Euro-Net C1 after 2 cycles of AEPA.
To evaluate the safety of Adcetris (brentuximab vedotin) in the AEPA/CAPDac regimen in children with high risk HL.
To describe acute hematologic, neuropathic, and infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia and hospitalizations, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
To study the association between local failure and original lymph node region and volume of radiation (patterns of treatment failure).
To assess patient-reported symptoms and health-related quality of life in children with high risk HL compared to those treated on the unfavorable treatment arm of the St. Jude HOD99 study.

OUTLINE:

AEPA REGIMEN: Patients receive brentuximab vedotin on days 1, 8, and 15, etoposide on days 1 to 5, prednisone three times daily (TID) on days 1 to 15, and doxorubicin hydrochloride on days 1 and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

CAPDac REGIMEN: Patients receive cyclophosphamide on days 1 and 8, brentuximab vedotin days 1 and 8, prednisone TID on days 1 to 15, and dacarbazine on days 1 to 3. Treatment repeats every 21-28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Beginning 2-3 weeks after CAPDac chemotherapy, patients with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy undergo radiation therapy daily, 5 days a week for 3-4 weeks.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually for 5 years.

Enrollment

77 patients

Sex

All

Ages

Under 18 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed, previously untreated CD30+ classical Hodgkin Lymphoma (HL). (Participants receiving limited emergent radiation therapy (RT) or steroid therapy - maximum of 7 days - because of cardiopulmonary decompensation or spinal cord compression will be eligible for protocol enrollment).
Age ≤ 18 years at the time of diagnosis (i.e., participants are eligible until their 19th birthday).
Ann Arbor stage IIB, IIIB, IVA, or IVB.
Adequate renal function based on GFR ≥ 70 ml/min/1.73m^2 or serum creatinine adjusted for age and gender.
Adequate hepatic function (total bilirubin < 1.5 x ULN for age, and SGOT/SGPT < 2.5 x ULN for age).
Female participant who is post-menarchal must have a negative urine or serum pregnancy test.
Female or male participant of reproductive potential must agree to use an effective contraceptive method throughout duration of study treatment.

Exclusion criteria

CD30 negative HL.
Has received prior therapy for Hodgkin lymphoma, except as noted above.
Inadequate organ function as described above.
Inability or unwillingness of research participant or legal guardian / representative to give written informed consent.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

77 participants in 1 patient group

Treatment

Experimental group

Description:

Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). Filgrastim may be given as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy will be given. Some participants may volunteer to complete the quality of life assessment.

Treatment: