Bortezomib, Ifosfamide, and Vinorelbine Tartrate in Treating Young Patients With Hodgkin's Lymphoma That is Recurrent or Did Not Respond to Previous Therapy
Condition: Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Childhood Lymphocyte Depletion Hodgkin Lymphoma; Childhood Lymphocyte Predominant Hodgkin Lymphoma; Childhood Mixed Cellularity Hodgkin Lymphoma; Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma; Childhood Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Childhood Hodgkin Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease; Recurrence; Sclerosis
Intervention: ifosfamide; bortezomib; vinorelbine tartrate; filgrastim
Intervention description: Given IV; Given IV; Given IV; Given IV or SC
Intervention MeSH terms: Bortezomib; Vinorelbine; Ifosfamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Maximum age: 29 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and efficacy of bortezomib with ifosfamide and
      vinorelbine in children and young adults with Hodgkin's lymphoma that was recurrent or did
      not respond to previous therapy. Bortezomib is an inhibitor of protein degradation.
      Bortezomib degrades short-lived regulatory proteins in the cell, and has been reported to
      increase the tumor cells. Bortezomib may increase the effectiveness of ifosfamide and
      vinorelbine (two standard drugs given to children with Hodgkin Lymphoma that has come back
      after initial treatment) by making cancer cells more sensitive to effectiveness of standard
      chemotherapy by preventing anti-death responses in these drugs. Giving bortezomib together
      with ifosfamide and vinorelbine tartrate should kill more cancer cells than are killed with
      ifosfamide and vinorelbine alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed Hodgkin's lymphoma at time of relapse or disease progression,
             meeting all of the following criteria:

               -  Stage I-IV disease

               -  No morphologically unclassifiable disease

          -  Meets 1 of the following criteria:

               -  Mixed cellularity

               -  Lymphocytic depletion (LD)

               -  LD, diffuse fibrosis

               -  LD, reticular

               -  Lymphocyte predominance (LP)

               -  LP, diffuse

               -  LP, nodular

               -  Nodular sclerosis (NS)

               -  NS, cellular phase

               -  NS, lymphocytic predominance

               -  NS, mixed cellularity

               -  NS, LD

               -  Not otherwise specified

          -  Primary refractory disease OR disease in first relapse, except for the following:

               -  Patients who achieved a complete response after treatment on protocol
                  COG-AHOD0431 who experience a biopsy-proven recurrence after doxorubicin
                  hydrochloride, vincristine, prednisone, and cyclophosphamide without
                  involved-field radiotherapy

               -  Patients on the observation-only arm of protocol COG-AHOD0431

          -  Any measurable, focal mass lesion of a visceral organ (e.g., liver, spleen, or kidney)

          -  Patients with metastatic disease to bone marrow and granulocytopenia, anemia, and/or
             thrombocytopenia are allowed provided both of the following criteria are met:

               -  Platelet count ≥ 20,000/mm³ (platelet transfusion allowed)

               -  Hemoglobin ≥ 8 g/dL (packed red blood cell transfusion allowed)

          -  Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lanksy
             PS 60-100% (for patients =< 16 years of age)

          -  Life expectancy >= 2 months

          -  Absolute neutrophil count >= 1,000/mm^3

          -  Platelet count >= 75,000/mm^3 (transfusion independent) (for patients with no bone
             marrow involvement)

          -  Creatinine =< 1.5 times upper limit of normal (ULN)

          -  Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2

          -  AST and ALT =< 2.5 times ULN

          -  Bilirubin =< 1.5 times ULN

          -  Shortening fraction >= 27% by echocardiogram OR LVEF >= 50% by gated radionuclide
             study

          -  Patients with a seizure disorder are eligible if on a nonenzyme-inducing
             anticonvulsant and seizures are well controlled

          -  No CNS toxicity > grade 2

          -  No serious intercurrent illnesses

          -  No known hypersensitivity to E. coli-derived proteins, filgrastim (G-CSF), or any
             component of the study drugs

          -  No peripheral neuropathy > grade 1

          -  No known hypersensitivity to bortezomib, boron, or mannitol

          -  No other concurrent chemotherapy or immunomodulating agents (including steroids)

               -  Concurrent corticosteroids allowed for treatment or prophylaxis of anaphylactic
                  reactions

               -  No dexamethasone or aprepitant as an antiemetic

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Recovered from prior therapy

          -  No prior bortezomib or other proteasome inhibitors

          -  At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas)

          -  More than 14 days since prior investigational drugs

          -  No concurrent enzyme inducing anticonvulsants that alter p450 metabolism, including
             phenytoin, carbamazepine, phenobarbital, or other anticonvulsants

               -  Benzodiazepine or gabapentin allowed