Trial Information

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

OBJECTIVES:

Primary

- To determine the progression-free survival (PFS) at 36 months from enrollment of
patients with bulky stage I or II Hodgkin lymphoma treated with ABVD alone or followed
by escalated BEACOPP and involved-field radiation therapy.

Secondary

- To evaluate the complete response rate in patients diagnosed with bulky stage I and II
Hodgkin lymphoma following PET-response-adapted chemotherapy with or without
radiotherapy.

- To determine the predictive value of semiquantitative evaluation of fludeoxyglucose
(FDG) uptake using various semiquantitative approaches at baseline, after 2 courses of
ABVD, and after completion of therapy.

- To determine the predictive value of volumetric vs 2-dimensional (2-D) measurement
changes on CT scan between baseline and after 2 courses, at the end of chemotherapy
(PET negative patients only), and after radiotherapy (PET positive patients only), and
compare with PET parameters.

- To determine if changes in both qualitative and semiquantitative FDG-PET
findings/changes between baseline and after course 2, at the end of chemotherapy (PET
negative patients only), and after radiotherapy (PET positive patients only) with
combination analyses incorporating changes obtained from dedicated CT scans, correlates
with response and PFS.

- To compare the predictive value of both qualitative and semiquantitative FDG-PET
changes, 2-D and volumetric CT changes, and combinatorial analyses (PET + dedicated CT
data) with molecular parameters and conventional parameters, including International
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 elevation of serial serum sCD30, IL10, CCL17,
or CCL22 correlate with relapse/progression or PET scan results.

- To confirm independently useful tissue biomarkers (bcl-2, MAL, FOXP3, GzB) for risk
stratification in patients with bulky stage I or II Hodgkin lymphoma treated with this
regimen.

OUTLINE: This is a multicenter study.

- ABVD chemotherapy: All patients receive doxorubicin hydrochloride IV over 3-5 minutes,
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 then undergo a PET/CT scan
and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis.
Patients who are PET-positive proceed to escalated BEACOPP chemotherapy. Patients who
are PET-negative receive 4 additional courses of ABVD chemotherapy in the absence of
disease progression or unacceptable toxicity.

- Escalated BEACOPP chemotherapy: Patients receive doxorubicin hydrochloride IV over 3-5
minutes and cyclophosphamide IV over 60 minutes on day 1; etoposide IV over 60 minutes
on days 1, 2, and 3; oral procarbazine hydrochloride once daily on days 1-7; oral
prednisone 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. Patients undergo another PET/CT scan and CT scan of the neck (if
it was positive at baseline), chest, abdomen, and pelvis. Patients then undergo
involved-field radiation therapy 5 days per week for 3½ weeks (for a total of 30.6 Gy).

Within 3-8 weeks after completion of chemotherapy, patients undergo an additional PET/CT
scan (utilizing fludeoxyglucose F 18) and CT scan of the neck (if it was positive at
baseline), chest, abdomen, and pelvis. Patients who are PET-negative proceed to follow up.
Patients who are PET-positive undergo a 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 a biopsy is neither clinically appropriate nor medically feasible
proceed to follow up. Patients who defer the biopsy undergo scanning 3 months later and then
undergo biopsy as above.

Blood and serum samples may be collected periodically for biomarker and IHC analysis.

After completion of study treatment, patients are followed up every 3 months for 1 year,
every 6 months for 2 years, and then annually for 7 years.