Pentostatin in Treating Patients With Refractory Chronic Graft-Versus-Host Disease
Condition: Graft Versus Host Disease
MeSH terms: Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
Intervention: pentostatin
Intervention description: 4 mg/sq m IV infusion over 20-30 min q 2 weeks
Intervention MeSH terms: Pentostatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      RATIONALE: Pentostatin may be effective in treating chronic graft-versus-host disease by
      stopping the immune system from rejecting donor stem cells or donor white blood cells.

      PURPOSE: This phase II trial is studying how well pentostatin works in treating patients with
      chronic graft-versus-host disease that is refractory (not responsive) to treatment with
      steroids.
    

Eligibility criteria:

        1. Histologic documentation of chronic GvHD following allogeneic HCT or donor lymphocyte
             infusion.

          2. Patients may have progressive, quiescent, or de novo onset chronic GvHD.

          3. Patients with extensive stage chronic GvHD requiring systemic immunosuppressive
             therapy are eligible. Patients with limited stage disease are excluded. Extensive
             stage is defined according to Seattle criteria (9) as either:

               -  Generalized skin involvement or

               -  Limited skin involvement or hepatic involvement with any one of the following:

                    -  Liver histology showing chronic progressive hepatitis, bridging necrosis or
                       cirrhosis

                    -  Eye involvement (Schirmer's test with < 5 mm wetting)

                    -  Involvement of minor salivary glands or oral mucosa

                    -  Involvement of any other organ

          4. Patients must have failed treatment with, or experience progression after, prior
             corticosteroids for extensive stage chronic GvHD, as defined below.

             4.1 Patients will be considered to have failed corticosteroids if they have any one of
             the following criteria:

               -  Progressive disease or less than a minor response in any organ system despite 2
                  weeks on corticosteroid treatment at least 1 mg/kg methylprednisolone or
                  equivalent.

               -  Failure to achieve at least a minor response after at least 4 weeks of treatment
                  with a dose of ≥ 0.5 mg/kg methylprednisolone or equivalent.

               -  Achievement of less than a partial response at 8 weeks of corticosteroid
                  treatment despite use of a dose ≥ 0.5 mg/kg methylprednisolone or equivalent.

               -  Requirement of ≥ 0.5 mg/kg methylprednisolone or equivalent to maintain a partial
                  response or better at 12 weeks of corticosteroid treatment.

               -  Requirement of > 10 mg/kg methylprednisolone or equivalent to maintain a partial
                  response or better at 18 weeks of corticosteroid treatment.

             4.2 Patients with progression of extensive stage chronic GvHD after a prior history of
             treatment with at least 18 weeks of corticosteroids, now requiring the reintroduction
             of corticosteroids (> 10 mg/day methylprednisolone or equivalent) or an additional
             agent (including photopheresis, PUVA) for treatment.

          5. Patients with established chronic GvHD not improving or progressing on other
             immunosuppressive agents are also eligible if steroid refractoriness has been
             established previously.

          6. Age ≥ 18 years

          7. Performance Status 0-3

          8. Patients on mechanical ventilation are excluded.

          9. No active infection. Patients with active infection requiring antibiotic therapy are
             not eligible until infection is controlled.

         10. No HIV infection. Patients with HIV infection are excluded because of safety concerns
             in this patient population.

         11. Non-pregnant and non-nursing. Women and men of reproductive potential should agree to
             use an appropriate method of birth control throughout their participation in this
             study due to the teratogenic potential of the therapy utilized in this trial (although
             it is unlikely that successful pregnancy will occur in patients with chronic GvHD).
             Appropriate methods of birth control include oral contraceptives, implantable hormonal
             contraceptives (Norplant®), or double barrier method (diaphragm plus condom).

         12. Required Initial Laboratory Values:

               -  Calc. Creatinine Clearance ≥ 30 mL/min/1.73 m^2

               -  ANC > 1000/μL

               -  Platelets > 50,000/μL without transfusion