Combination Chemotherapy and Radiation Therapy in Treating Patients Who Are Undergoing an Autologous Stem Cell Transplant for Relapsed or Refractory Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: 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 and radiation
      therapy with an autologous stem cell transplant, using peripheral stem cells or bone marrow
      from the patient, may allow more chemotherapy to be given so that more cancer cells are
      killed. Giving combination chemotherapy together with radiation therapy before an autologous
      stem cell transplant may be an effective treatment for Hodgkin's lymphoma.

      PURPOSE: This phase II trial is studying how well combination chemotherapy and radiation
      therapy work in treating patients who are undergoing an autologous stem cell transplant for
      relapsed or refractory Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine whether event-free survival of patients with low to high-intermediate risk,
           relapsed or refractory Hodgkin's lymphoma can be improved when treated with
           cytoreductive combination chemotherapy followed by radiotherapy, high-dose combination
           chemotherapy, and autologous stem cell transplantation.

      Secondary

        -  Determine the toxic effects of this regimen in these patients.

      OUTLINE: Patients are stratified according to risk factors (low or low-intermediate risk [0-1
      risk factor] vs high-intermediate risk [2 risk factors]).

        -  ICE-based cytoreductive chemotherapy: Patients are assigned to 1 of 2 treatment groups.

             -  Group I (patients with low or low-intermediate risk disease): Patients receive ICE
                comprising ifosfamide IV and carboplatin IV once on day 2 and etoposide IV over 1
                hour once daily on days 1-3. Patients then receive ifosfamide IV twice on day 15,
                carboplatin IV once on day 17 and etoposide IV over 1 hour twice daily on days
                15-17.

             -  Group II (patients with high-intermediate risk disease): Patients receive
                ifosfamide IV twice on days 1 and 17, carboplatin IV once on days 3 and 19, and
                etoposide IV over 1 hour twice daily on days 1-3 and 17-19.

      In both groups, patients undergo stem cell collection after either the first or second OR
      first and second courses of ICE.

        -  Stem cell mobilization and collection: Patients receive filgrastim (G-CSF)
           subcutaneously (SC) beginning on day 5 and continuing until stem cell collection is
           completed. Patients undergo a maximum of 5 daily apheresis sessions. Patients who
           mobilize fewer than the required minimal number of stem cells repeat apheresis with
           high-dose G-CSF alone or undergo bone marrow harvest. Patients then proceed to
           radiotherapy, high-dose chemotherapy (HDC), and autologous stem cell transplant (ASCT)
           OR noncross-resistant chemotherapy based on response to ICE-based cytoreductive
           chemotherapy.

        -  Restaging studies: Patients undergo restaging studies with CT scan and positron emission
           tomography (PET). Patients who are chemosensitive with a normal PET scan proceed to
           radiotherapy, HDC, and ASCT. Patients who progress on ICE, or who respond but have an
           abnormal PET scan, proceed to noncross-resistant chemotherapy comprising gemcitabine
           hydrochloride, vinorelbine, and doxorubicin HCl liposome (GND).

        -  GND chemotherapy: Patients receive gemcitabine hydrochloride IV, vinorelbine IV, and
           doxorubicin HCl liposome IV on days 1, 15, 29, and 43. Patients then proceed to
           radiotherapy, HDC, and ASCT in the absence of disease progression.

        -  Radiotherapy: Within 2 weeks after completion of the ICE or GND regimen, patients who
           have no history of prior radiotherapy receive radiotherapy according to stratification
           by disease extent (isolated lymph nodes vs ≥ 2 contiguous nodal-based masses with or
           without extensive small-volume lymphadenopathy vs extensive small-volume
           lymphadenopathy). These patients undergo either involved-field radiotherapy (IFRT) twice
           daily over 1-2 weeks, total lymphoid irradiation (TLI) twice daily over 1 week, or both
           concurrently.

        -  HDCT: Patients who undergo TLI only OR IFRT and TLI receive high-dose cyclophosphamide
           IV twice daily and etoposide IV once daily on days -5 and -2. Patients who undergo IFRT
           only OR do not undergo radiotherapy receive high-dose cyclophosphamide IV twice daily
           and etoposide IV once daily on days -6 and -3 and carmustine IV once on day -2.

        -  ASCT: Patients undergo ASCT or reinfusion of bone marrow, if harvested, on day -1 or 0.
           Patients then receive G-CSF beginning on day 5 and continuing until blood counts
           recover.

      After completion of study treatment, patients are followed periodically for 15 months.
    

Intervention name(s): carboplatin; etoposide; ifosfamide
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Given IV; Given IV; Given IV
Intervention MeSH terms: Carboplatin; Etoposide; Ifosfamide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult lymphocyte depletion Hodgkin lymphoma; adult mixed cellularity Hodgkin lymphoma; adult nodular sclerosis Hodgkin lymphoma; recurrent adult Hodgkin lymphoma