Chemotherapy Based on Positron Emission Tomography Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies how well chemotherapy based on positron emission tomography (PET)
      scan works in treating patients with stage I or stage II Hodgkin lymphoma. Drugs used in
      chemotherapy work in different ways to stop the growth of cancer cells, either by killing the
      cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy)
      may kill more cancer cells. Radiation therapy uses high energy x-rays to kill cancer cells.
      Giving combination chemotherapy together with radiation therapy may kill more cancer cells
      and allow doctors to save the part of the body where the cancer started. Comparing results of
      diagnostic procedures, such as PET scan, done before, during, and after chemotherapy may help
      doctors predict a patient's response to treatment and help plan the best treatment.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the progression-free survival (PFS) from enrollment for patients with
      non-bulky stage I and II Hodgkin lymphoma.

      II. To compare the PFS of patients who are PET positive versus PET negative following 2
      cycles of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD).

      SECONDARY OBJECTIVES:

      I. To evaluate the complete response (CR) rate of patients diagnosed with non-bulky stage I
      and II Hodgkin lymphoma following PET response-adapted chemotherapy with or without radiation
      therapy.

      II. To determine the predictive value of fludeoxyglucose (FDG) uptake using various
      semi-quantitative approaches, at baseline, after 2 cycles of AVBD and at completion of
      therapy.

      III. To determine the predictive value of volumetric changes on computed tomography (CT) vs
      2-dimensional (2-D) analyses after 2 cycles and 4 cycles and compare with PET parameters with
      and without combination analyses (PET + dedicated CT data).

      IV. To compare the predictive value of metabolic parameters/changes that are measured both
      visually and semi-quantitatively, International Harmonization Project (IHP) criteria, 2-D and
      volumetric CT changes, molecular parameters, and conventional parameters, including
      International Prognostic Score (IPS).

      V. To assess whether elevated baseline circulating markers of inflammation (including soluble
      cluster of differentiation CD30 [sCD]30, soluble CD 163 [CD163], interleukin-10 (IL10),
      chemokine (C-C motif) ligand 17 (CCL17), and chemokine (C-C motif) ligand 22 [CCL22])
      correlate with clinical response and PFS and PET scan results.

      VI. To assess whether persistent or recurrent elevated serial circulating markers of
      inflammation (including soluble CD30 [sCD30], soluble CD163 [sCD163], IL10, CCL17, or CCL22)
      correlate with relapse/progression or PET scan results.

      VII. To confirm independently useful tissue biomarkers for risk stratification in patients
      with non-bulky stage I and II Hodgkin lymphoma treated with this regimen.

      VIII. To compare mediastinal bulk on standing posterior-anterior (PA) and lateral chest x-ray
      (> 0.33 maximum chest diameter) with chest CT (mass > 10 cm).

      OUTLINE:

      ABVD CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (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, procarbazine orally (PO) on days 1-7, prednisone PO 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.

      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.
    

Intervention name(s): Bleomycin Sulfate; Doxorubicin Hydrochloride; Procarbazine Hydrochloride; Vinblastine Sulfate; Dacarbazine; Cyclophosphamide; Etoposide phosphate; prednisone; Radiation Therapy; Fludeoxyglucose F-18; computed tomography; Positron Emission Tomography
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Radiation; Procedure; Procedure
Intervention description(s): Given IV; Given IV; Given PO; Given IV; Given IV; Given IV; Given IV; Given PO; Undergo radiation therapy; Undergo FDG PET/CT; Undergo FDG PET/CT; Undergo FDG PET/CT
Intervention MeSH terms: Prednisone; Cyclophosphamide; Dacarbazine; Doxorubicin; Liposomal doxorubicin; Etoposide; Bleomycin; Vinblastine; Etoposide phosphate; Procarbazine; Fluorodeoxyglucose F18
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I adult Hodgkin lymphoma; stage II adult Hodgkin lymphoma