Trial Information

Phase II Trial of Response-Adapted Therapy Based on Positron Emission Tomography (PET) for Bulky Stage I and II Classical Hodgkin Lymphoma (HL)

OBJECTIVES:

Primary

- To evaluate the progression-free survival (PFS) at 36 months following registration for
patients who are positron emission tomography (PET) negative after 2 courses of
chemotherapy, and receive 4 additional courses of doxorubicin hydrochloride, bleomycin
sulfate, vinblastine, and dacarbazine (ABVD) followed by involved-nodal radiotherapy
[INRT] of 30-30.6 Gy.

Secondary

- To evaluate the PET-negative rate after 2 courses of ABVD chemotherapy in patients with
stage I/II Hodgkin lymphoma with bulky mediastinal disease.

- To evaluate the PFS at 36 months for patients who are PET positive after 2 courses of
chemotherapy and receive 4 courses of escalated bleomycin sulfate, etoposide,
doxorubicin hydrochloride, cyclophosphamide, vincristine sulfate, procarbazine
hydrochloride, and prednisone (BEACOPP) followed by INRT of 30-30.6 Gy.

- To evaluate the complete response (CR) rate and overall survival (OS) for PET-positive
and PET-negative patients after 2 courses of ABVD.

- To identify sites of relapse following combined-modality therapy (CMT) for patients
with large mediastinal adenopathy and correlate with RT fields.

- To assess toxicity on both arms of study.

- To assess reproductive function at baseline and at 3 years after ABVD or escalated
BEACOPP with specific serum markers.

- To bank serum and plasma at baseline and selected time points to assess the prognostic
value of various markers such as, but not limited to, SCD30, IL10, CCL17, CCL22, and
MDC.

- To create tissue microarrays (TMAs) from patient tumor blocks for future biomarker
assessment including, but not limited to, bcl-2, FOXP3, and macrophage content.

- To measure serum TARC levels pre-treatment and post two courses of ABVD and correlate
with PET-CT findings (performed at same time points) and 3 year PFS.

Tertiary

- To assess the predictive value of fludeoxyglucose F 18 (18FDG) uptake, as measured by
semi-quantitative measurements including standard uptake variables (SUVs), with respect
to response at the end of chemotherapy and PFS.

- To compare the predictive value for response and PFS of FDG uptake alone to that of FDG
uptake in combination with CT size change information.

- To compare the predictive value for response and PFS of FDG uptake alone to that of FDG
uptake in combination with available serum and tissue molecular biomarkers.

- To compare the results of the secondary imaging objectives with the corresponding CALGB
50801 results (contingent on reaching agreement with CALGB on the combined analysis of
the two studies).

OUTLINE: This is a multicenter study.

Induction ABVD chemotherapy: Patients receive doxorubicin hydrochloride IV, bleomycin
sulfate IV, 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 in the absence of disease progression
or unacceptable toxicity.

Patients are then assigned to an intervention arm according to fludeoxyglucose F 18 (18 FDG)
positron emission tomography (PET)/computed tomography (CT) results (negative vs positive).

- ABVD (18FDG-PET/CT negative): Patients receive doxorubicin hydrochloride, bleomycin
sulfate, vinblastine, and dacarbazine as in induction chemotherapy. Treatment repeats
every 28 days for 4 courses in the absence of disease progression or unacceptable
toxicity. Within 3-6 weeks after completion of chemotherapy, patients undergo
involved-node radiotherapy (INRT) 5 days a week for approximately 3½ weeks.

- Escalated or standard BEACOPP* (18FDG-PET/CT positive): Patients receive doxorubicin
hydrochloride IV and cyclophosphamide IV over 60 minutes on day 1, etoposide IV over 60
minutes on days 1-3, procarbazine hydrochloride orally (PO) on days 1-7, prednisone PO
on days 1-14, and bleomycin sulfate IV and vincristine sulfate IV on day 8. Treatment
repeats every 21 days for 4 courses in the absence of disease progression or
unacceptable toxicity. Within 3-6 weeks after completion of chemotherapy, patients who
achieve complete response with a negative 18FDG-PET/CT scan undergo INRT 5 days a week
for approximately 3½ weeks.

NOTE: *HIV-positive patients whose 18FDG-PET/CT scans are positive after two courses of
induction ABVD receive 4 courses of standard BEACOPP followed by INRT.

Patients undergo 18FDG-PET scans at baseline, and within 8-10 days after 2 courses of ABVD
induction chemotherapy. Patients also undergo 18FDG-PET/CT** scan within 3-8 weeks after
completion of 4 courses of BEACOPP and 6 courses of ABVD, and 3 months after completion of
INRT.

NOTE: **If PET/CT remains positive, then a biopsy may be performed if medically appropriate
or clinically feasible at the discretion of the treating physician. If biopsy is positive,
patients will be followed for survival and secondary malignancies or new primaries.

Patients may undergo blood sample collection for correlative studies.

After completion of study therapy, patients are followed up every 3 months for 1 year, every
6 months for 2 years, and then annually for up to 10 years.