AHOD1331

Principal Investigator: Phillip Barnette
Keywords: Pediatrics , Oncology , Hodgkin Lymphoma Department: Pediatric Administration
IRB Number: 00081687 Co Investigator:  
Specialty: Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Jennifer Craig
jennifer.craig@imail.org
8016624715

Brief Summary

1.1 Primary Aim: To assess the event free survival (EFS) of a novel regimen incorporating brentuximab vedotin (Bv; AdcetrisTM) in the chemotherapy backbone of doxorubicin (Adriamycin), vincristine, etoposide, prednisone and cyclophosphamide (Bv-AVEPC) in newly diagnosed high-risk cHL compared to those treated with ABVE-PC.

1.2 Secondary Aims:

1.2.1 To determine whether children/young adults with high-risk cHL treated with Bv-AVEPC have a higher rate of early response (determined by FDG-PET) and a reduction in response-directed radiation therapy (RT) compared to those treated with ABVE-PC.

1.2.2 To compare the rate of neuropathy (> Grade 3) among patients treated on the Bv-AVEPC (experimental arm) to patients treated on the ABVE-PC (standard arm).

1.3 Exploratory Aims:

Childhood International Prognostic Score (CHIPS)

1.3.1 To validate and compare the Childhood Hodgkin International Prognostic Score (CHIPS) to conventional Ann Arbor Stage (Stages II B with bulk, III B, IV A or B) in predicting outcome in high-risk childhood cHL.

Biology

1.3.2 To determine the incidence of preferentially expressed antigen in melanoma (PRAME) and testis-specific antigens in EBV- cHL tumors and the incidence of EBV antigens (EBNA1, LMP1, LMP2) in EBV+ cHL tumors, with the goal of developing strategies to integrate cellular therapy into treatment for newly diagnosed high-risk cHL.

Imaging

1.3.3 To incorporate qualitative visual FDG-PET into response-directed treatment algorithms and explore quantitative FDG-PET and CT definitions of tumor burden and response for incorporation into next generation pediatric cHL risk-stratification schemes, exploring the extension of these algorithms to young adults.

Radiation Therapy

1.3.4 To evaluate the reduction in normal tissue irradiation associated with the current treatment approach compared to the volume of historic IFRT fields.

1.3.5 To evaluate EFS and patterns of relapse following protocol-specified RT utilization and treatment volumes.

Patient Reported Outcomes (PRO) of Peripheral Neuropathy and Health-Related Quality of Life

1.3.6 To characterize the extent of chemotherapy induced peripheral neuropathy (CIPN), as reported by patients and parent proxies, through serial administration of the FACT-GOG-NTX.

1.3.7 To describe the Health-Related Quality of Life (HRQL) consequences of peripheral neuropathy over time by correlating total neuropathy scale scores with the individual items with the CHRIs-Global scale (e.g., physical health, pain, emotional functioning).

1.3.8 To perform a cross validation of the FACT-GOG-NTX with the TNS-PV to determine the performance of both measures with the use of brentuximab vedotin in a limited institutional approach in children and young adults with cHL.

Economic (For US Institutions Only)

1.3.9 To assess the resource use and cost implications of Bv in combination with chemotherapy and radiotherapy (RT) for newly diagnosed high-risk cHL in children and young adults.

Follow-up of Deauville score 3 lesions on FDG-PET imaging (confirmed by central imaging review)
1.3.10 To estimate the risk of relapse among RRL subjects that have at least one lesion that is Deauville 3 at PET 2.


The pharmacokinetics of brentuximab vedotin
1.3.11 To characterize the pharmacokinetics of brentuximab vedotin in children <13 years of age.

 

Inclusion Criteria

INCLUSION CRITERIA

3.2.1 Age

Ages > 2 - < 22 years.

3.2.2 Diagnosis

Patients with newly diagnosed, pathologically confirmed cHL meeting one of the following Ann Arbor stages are eligible:

• Stage IIB with bulk*

• Stage IIIB

• Stage IVA

• Stage IVB

* If study eligibility by staging is uncertain, consultation with IROC RI may be obtained prior to study enrollment.

3.2.3 Organ Function Requirements

3.2.3.1 Adequate Renal Function Defined As:

- Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or

- A serum creatinine based on age/gender as follows:

Age

Maximum Serum

Creatinine (mg/dL)

Male

Female

2 to < 6 years

0.8

0.8

6 to < 10 years

1

1

10 to < 13 years

1.2

1.2

13 to < 16 years

1.5

1.4

≥ 16 years

1.7

1.4

Exclusion Criteria

3.2.4.1 Patients with nodular lymphocyte-predominant HL.

3.2.4.2 Patients with an immunodeficiency that existed prior to diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible.

3.2.4.3 Patients who are pregnant. (Since fetal toxicities and teratogenic effects have been noted for several of the study drugs, a negative pregnancy test is required for female patients of childbearing potential).

3.2.4.4 Lactating females who plan to breastfeed.

3.2.4.5 Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 30 days after the last dose of chemotherapy.

3.2.4.6 Patients known to be positive for HIV are not eligible.

3.2.4.7 Patients who have received any previous chemotherapy or radiation therapy are not eligible.

3.2.4.8 Patients who received systemic corticosteroids within 28 days of enrollment on this protocol, except as specified, are not eligible.

Note: Please see Protocol for the concomitant therapy restrictions for patients during treatment.