Cyclophosphamide, Rituximab, and Either Prednisone or Methylprednisolone in Treating Patients With Lymphoproliferative Disease After Solid Organ Transplantation
Condition: Lymphoproliferative Disorder
MeSH terms: Lymphoproliferative Disorders
Intervention: rituximab; cyclophosphamide; methylprednisolone; prednisone
Intervention description: Cycles 1 and 2 only: Given IV Incremental: First dosage: < 21 years of age: 0.5mg/kg/hr (maximum of 50 mg/hr) for the 1st hour ≥ 21 years of age: 50 mg/hr for the 1st hour. Subsequent dosages: < 21 years of age: 1.0mg/kg/hr (maximum of 50 mg/hr) for the 1st hour ≥ 21 years of age: 100 mg/hr for the 1st hour. Days 1, 8 and 15.; Given IV over 30-60 minutes Dose 600 mg/m2 in 50-250 mL of normal saline (NS) or Dextrose-Water 5%(D5W) (at a maximum concentration of 20 mg/ml) over 30-60 minutes on day 1 of each cycle; Methylprednisolone 0.8 mg/kg IV over 12 hours on days 1,2,3,4 and 5 of each cycle.; Dosage 1 mg/kg orally every 12 hours on days 1,2,3,4 and 5 of each cycle. Oral prednisone may be rounded up to the nearest 2.5 mg as necessary for tablet size
Intervention MeSH terms: Prednisone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Rituximab; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Maximum age: 30 Years
Healthy volunteers: No
Keywords: post-transplant lymphoproliferative disorder

Summary:

      RATIONALE: Drugs used in chemotherapy such as cyclophosphamide, prednisone, and
      methylprednisolone use different ways to stop cancer cells from dividing so they stop growing
      or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them
      or deliver cancer-killing substances to them without harming normal cells. Combining
      cyclophosphamide and either prednisone or methylprednisolone with rituximab may be effective
      in treating lymphoproliferative disease following organ transplantation.

      PURPOSE: Phase II trial to study the effectiveness of combining cyclophosphamide and either
      prednisone or methylprednisolone with rituximab in treating patients who have Epstein-Barr
      virus-positive lymphoproliferative disease following organ transplantation.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed post-transplant lymphoproliferative disease (PTLD)

               -  Presents with 1 of the following:

                    -  Fulminant PTLD (F-PTLD)

                         -  Fever greater than 38°C

                         -  Hypotensive (for age)

                         -  Evidence of multiple organ involvement/failure, including at least 2 of
                            the following:

                              -  Marrow (including pancytopenia without detectable B-cell
                                 proliferation)

                              -  Liver (coagulopathy, transaminitis, and/or hyperbilirubinemia)

                              -  Lungs (interstitial pneumonitis with or without pleural effusions)

                              -  Gastrointestinal tract hemorrhage

                    -  Non-fulminant PTLD (NF-PTLD)

                         -  Does not meet the above F-PTLD criteria

                         -  Considered medically refractory to reduced immune suppression (50% or
                            more reduction of immunosuppression) for at least 1 week

          -  CD20 positive AND Epstein-Barr virus positive

          -  Must have received prior solid organ transplantation

          -  Must have residual disease after biopsy and/or surgery

          -  No PTLD central nervous system (CNS) disease, defined as positive cytology and/or
             radiographic evidence

        PATIENT CHARACTERISTICS:

        Age

          -  Under 31

        Performance status

          -  Not specified

        Life expectancy

          -  NF-PTLD patients:

               -  At least 8 weeks

        Hematopoietic

          -  See Disease Characteristics

        Hepatic

          -  See Disease Characteristics

        Renal

          -  Not specified

        Pulmonary

          -  See Disease Characteristics

        Other

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception

          -  HIV negative

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  More than 1 month since prior rituximab

        Chemotherapy

          -  More than 4 weeks since prior chemotherapy and recovered

        Endocrine therapy

          -  Not specified

        Radiotherapy

          -  Not specified

        Surgery

          -  See Disease Characteristics