Response-Based Therapy Assessed By PET Scan in Treating Patients With Bulky Stage I and Stage II Classical Hodgkin Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      This research is being done in order to improve treatment outcomes in patients diagnosed with
      bulky, early stage Hodgkin lymphoma and to reduce the side effects that are associated with
      use of radiation used in current treatments. The chemotherapy treatment in this study
      consists of a combination of four drugs approved by the Food and Drug Administration (FDA):
      doxorubicin, bleomycin, vinblastine, and dacarbazine. This regimen (called ABVD) has been
      found to be effective in treating patients with Hodgkin lymphoma and is considered the
      standard of treatment used with radiation therapy in patients with bulky early stage Hodgkin
      lymphoma. As part of the evaluation of the effectiveness of the chemotherapy treatment, PET
      scans will be obtained during the course of therapy. The usefulness of this PET scan will be
      evaluated to determine whether radiation may be left out in the treatment of disease if the
      PET scan shows that the patient has responded to chemotherapy alone. The plan is to identify
      a group of patients using early PET scans in order to change to a chemotherapy treatment
      called BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine,
      procarbazine and prednisone). It is one of the most highly effective chemotherapy regimens
      for Hodgkin lymphoma, but is associated with more side effects than ABVD. Although it has
      become standard of care in Europe, its use has been more limited in the U.S. because of
      concerns about toxicity.
    

Detailed description: 
      This is single-arm phase II clinical trial of response-adapted therapy based on PET for bulky
      stage I and stage II Hodgkin lymphoma. A maximum of 123 patients will be entered to the
      study. The primary outcome of this study is progression-free survival (PFS), defined as the
      time from study entry to disease progression or death.

      Primary Objective:

      To determine the progression-free survival (PFS) at 36 months from enrollment for patients
      with bulky stage I and II Hodgkin lymphoma. All patients will begin treatment with ABVD.
      Patients who are PET negative after 2 cycles of chemotherapy will receive 6 cycles of ABVD
      without radiotherapy. Patients who are PET positive after 2 cycles of ABVD will then receive
      4 cycles of escalated BEACOPP followed by IFRT. A comparison will be made of the 36-month PFS
      between patients who are PET positive and those who are PET negative following 2 cycles of
      ABVD.

      Secondary Objectives:

        1. To evaluate the complete response (CR) rate of patients diagnosed with bulky stage I and
           II Hodgkin lymphoma following PET response-adapted chemotherapy with or without
           radiation therapy.

        2. To determine the predictive value of FDG uptake using various semiquantitative
           approaches, at baseline, after 2 cycles of ABVD and at completion of therapy.

        3. To determine the predictive value of volumetric vs. 2 dimensional (2-D) measurement
           changes on CT between baseline and after 2 cycles, at the end of chemotherapy (PET
           negative patients only) and after RT (PET positive patients only) and compare with PET
           parameters.

        4. To determine if changes in both qualitative and semiquantitative FDG-PET findings
           between baseline and after cycle 2, at end of chemotherapy (PET negative patients only)
           and after RT (PET positive patients only) with combination analyses with incorporating
           changes obtained from dedicated CT scans, correlate with response and PFS.

        5. 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 IPS.

        6. To assess whether elevated baseline serum soluble CD30 (sCD30), IL10, CCL17, and CCL22
           correlate with clinical response and PFS.

        7. To assess whether persistent or recurrent elevation of serial serum sCD30, IL10, CCL17,
           or CCL22 correlate with relapse/progression or PET scan results.

        8. To confirm independently useful tissue biomarkers (bcl-2, MAL, FOXP3, CD68, GzB) for
           risk stratification in patients with bulky stage I and II Hodgkin lymphoma treated with
           this regimen.

        9. To compare mediastinal bulk on standing PA and lateral chest x-ray (> 0.33 maximum chest
           diameter) with chest CT (mass > 10 cm).

      After completion of study treatment, patients are followed up every 3 months for 1 year,
      every 6 months for 2-3 years, and then once a year for a maximum of ten years from the time
      of entry on the study.
    

Intervention name(s): ABVD; BEACOPP; radiation therapy
Intervention type(s): Drug; Drug; Radiation
Intervention description(s): doxorubicin 25 mg/m^2 IV bleomycin 10 units/m^2 IV vinblastine 6 mg/m^2 IV dacarbazine 375 mg/m^2 IV; bleomycin 10 units/m^2 IV on Day 8 etoposide 200 mg/m^2 IV on Days 1, 2 and 3 doxorubicin 35 mg/m^2 IV on Day 1 cyclophosphamide 1250 mg/m^2 IV on Day 1 vincristine 1.4 mg/m^2 IV on Day 8 procarbazine 100 mg/m^2 orally on Days 1-7 prednisone 40 mg/m^2 orally on Days 1-14
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I adult Hodgkin lymphoma; stage II adult Hodgkin lymphoma; adult favorable prognosis Hodgkin lymphoma; adult lymphocyte depletion Hodgkin lymphoma; adult lymphocyte predominant Hodgkin lymphoma; adult mixed cellularity Hodgkin lymphoma; adult nodular sclerosis Hodgkin lymphoma; adult unfavorable prognosis Hodgkin lymphoma