Trial Information

Phase II Trial of Response-Adapted Chemotherapy Based on Positron Emission Tomography for Non-Bulky Stage I and II Hodgkin Lymphoma

OBJECTIVES:

Primary

- To determine the progression-free survival (PFS) of patients with non-bulky stage I or
II Hodgkin lymphoma treated with ABVD alone or followed by escalated BEACOPP and
involved-field radiation therapy.

- To compare the PFS of patients who are PET positive versus PET negative after 2 courses
of ABVD.

Secondary

- To evaluate the complete response rate in patients treated with these regimens.

- To determine the predictive value of semiquantitative evaluation of FDG/PET uptake
using various approaches at baseline, after 2 courses of AVBD, and at completion of
therapy.

- To determine the predictive value of volumetric changes on CT scan after courses 2 and
4 of ABVD and compare with PET parameters with and without combination analyses
(PET+dedicated CT data).

- To compare the predictive value of metabolic parameters/changes both visual and
quantitative, IHP criteria, volumetric CT changes, molecular parameters, and
conventional parameters, including initial prognostic score.

- To assess whether elevated baseline serum soluble CD30 (sCD30), IL10, CCL17, and CCL22
correlate with clinical response and PFS.

- To assess whether persistent or recurrent elevated serial serum sCD30, IL10, CCL17, or
CCL22 correlate with relapse/progression or PET scan results.

- To confirm independently useful tissue biomarkers for risk stratification in patients
with non-bulky stage I and II Hodgkin lymphoma treated with these regimens.

- To compare mediastinal bulk on standing PA and lateral chest x-ray (> 0.33 maximum
chest diameter) with chest CT (mass > 10 cm).

OUTLINE: This is a multicenter study.

- ABVD chemotherapy: Patients receive doxorubicin hydrochloride IV over 3-5 minutes,
bleomycin sulfate IV over 3-5 minutes, vinblastine IV over 3-5 minutes, and dacarbazine
IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 2 courses.
Patients then undergo PET scan. Patients achieving complete response (CR), partial
response (PR), or stable disease (SD) with a negative PET scan receive 2 additional
courses of ABVD chemotherapy in the absence of disease progression or unacceptable
toxicity. Patients achieving CR, PR, or SD with a positive PET scan proceed to
escalated BEACOPP chemotherapy.

- Escalated BEACOPP* chemotherapy: Patients receive doxorubicin hydrochloride IV over 3-5
minutes and cyclophosphamide IV over 60 minutes on day 1, etoposide IV over 45-60
minutes on days 1-3, oral procarbazine on days 1-7, oral prednisone on days 1-14, and
bleomycin sulfate IV and vincristine IV on day 8. Treatment repeats every 21 days for 2
courses in the absence of disease progression or unacceptable toxicity. Within 4-6
weeks after completion of BEACOPP chemotherapy, patients undergo involved-field
radiotherapy (IFRT) 5 days a week for 3½ weeks.

NOTE: * HIV-positive patients receive standard BEACOPP instead of escalated BEACOPP.

Patients undergo fludeoxyglucose F^18 PET/CT scan at baseline, and within 8-10 days after
completion of chemotherapy. Patients also undergo additional PET/CT scans within 3-4 weeks
after completion of ABVD or within 12 weeks after completion of BEACOPP and IFRT. Patients
with a negative PET scan proceed to follow up. Patients with a positive PET scan undergo
biopsy**. Patients with a negative biopsy proceed to follow up, and patients with a positive
biopsy are treated at the discretion of the investigator.

NOTE: ** Patients for whom biopsy is neither clinically appropriate nor medically feasible
proceed to follow-up. Patients for whom biopsy is neither clinically indicated nor medically
appropriate undergo a repeat PET/CT scan after 3 months. If PET/CT scan remains positive,
patients undergo biopsy as above.

Patients may undergo blood sample collection for biomarker studies.

After completion of study therapy, patients are followed up every 3 months for 1 year, every
6 months for 2-3 years, and then annually for a maximum of 5 years.