Brentuximab Vedotin, Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients with Stage IIB or IIIB-IVB Hodgkin Lymphoma

Status: Closed to Accrual

Description

This phase II trial studies the side effects and how well brentuximab vedotin, combination chemotherapy, and radiation therapy work in treating younger patients with stage IIB or IIIB-IVB Hodgkin lymphoma. Monoclonal antibodies, such as brentuximab vedotin, find and attach to the surface of most lymphoma cells and may cause the cells to die. 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, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill cancer cells and shrink cancer. Giving brentuximab vedotin with combination chemotherapy and radiation therapy may kill more cancer cells and may also reduce the late side effects caused by chemotherapy or radiation therapy.

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed, previously untreated CD30+ classical 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)
  • Ann Arbor stage IIB, IIIB, IVA, or IVB
  • Glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or serum creatinine adjusted for age and gender as follows: * Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for males and 0.6 mg/dL for females * Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for males and 0.8 mg/dL for females * Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for males and 1 mg/dL for females * Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for males and 1.2 mg/dL for females * Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females * Age >= 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females
  • Total bilirubin < 1.5 x upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (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
  • Inadequate organ function as described
  • Inability or unwillingness of research participant or legal guardian/representative to give written informed consent

Locations & Contacts

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. 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).

II. To compare the event-free survival in high risk HL patients treated with AEPA/CAPDac to the historical control HOD99 unfavorable risk 2 arm (UR2).

SECONDARY OBJECTIVES:

I. To estimate the number of patients with adequate response according to the definitions in the European-Network (Euro-Net) C1 after 2 cycles of AEPA.

II. To evaluate the safety of Adcetris (brentuximab vedotin) in the AEPA/CAPDac regimen in children with high risk HL.

III. 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.

IV. To study the association between local failure and original lymph node region and volume of radiation (patterns of treatment failure).

V. To assess patient-reported symptoms and health-related quality of life in children with high risk HL compared to those treated on the unfavorable HOD99 treatment arm.

EXPLORATORY OBJECTIVES:

I. To compare the ratings of neuropathic toxicity according to the NCI Common Terminology Criteria for Adverse Events, version 4.0 to the Pain Quality Assessment Scale (PQAS).

II. To describe the pharmacokinetics of Adcetris when used as part of AEPA/CAPDac for pediatric HL patients. (Completed as of 09-11-2014)

III. To describe the immunogenicity of Adcetris and the relationship between early response and presence of anti-chimeric anti-body.

IV. To explore the association between cluster of differentiation (CD)30 density in Reed Sternberg cells in paraffin embedded tumor tissue and early response and event-free survival.

V. To explore the association between soluble CD30 (in serum/plasma) and early response, event-free survival.

VI. To identify pharmacogenetic predictors for treatment-related outcomes in the context of AEPA/CAPDac.

VII. Compare dosimetrically, the ability of proton-based radiation therapy (PBRT) to spare adjacent normal tissues compared to photon-based radiation therapy.

OUTLINE:

AEPA REGIMEN: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, prednisone orally (PO) three times daily (TID) on days 1-15, and doxorubicin hydrochloride IV over 1-6 hours 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 IV over 60 minutes on days 1 and 8, brentuximab vedotin IV over 30 minutes on days 1 and 8, prednisone PO TID on days 1-15, and dacarbazine IV over 15-30 minutes on days 1-3. Treatment repeats every 21 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.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
St. Jude Children's Research Hospital

Principal Investigator
Monika Metzger

Trial IDs

Primary ID HLHR13
Secondary IDs NCI-2013-01123
Clinicaltrials.gov ID NCT01920932