A Trial of Extracorporeal Photopheresis, Pentostatin, and Total Body Irradiation in Patients Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation for the Treatment of Malignancies
Condition: Hematologic Malignancies
MeSH terms: Neoplasms; Hematologic Neoplasms
Intervention: extracorporeal photopheresis; Pentostatin; Total Body Irradiation; Pentostatin; Total Body Irradiation
Intervention description: Extracorporeal photopheresis (ECP) is the ex vivo exposure of the leukocyte rich fraction to ultraviolet light in the presence of 8-methoxypsoralen.; pentostatin 8mg/m2 over 48 hours by continuous infusion; 600cGy TBI in 3 200cGy TBI fractions; pentostatin 8mg/m2 over 48 hours by continuous infusion; 600cGy TBI in 3 200cGy TBI fractions
Intervention MeSH terms: Pentostatin; Methoxsalen
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Allogeneic Stem Cell Transplant

Summary:

      This is a study to explore the use of a reduced intensity transplant conditioning regimen. A
      conditioning regimen is the treatment that is given to prepare a body for the new bone marrow
      that will be received from a donor. Reduced intensity conditioning uses lower doses of
      chemotherapy than conventional conditioning regimens. The use of lower doses of drugs and
      radiation cause fewer side effects. Reduced intensity regimens have been offered to older
      patients or patients at increased risk for transplant-related side effects and have been
      shown to be safe and effective. Reduced intensity conditioning regimens are now considered
      for many patients who are undergoing transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must give informed consent to receive study treatment.

          -  Availability of a suitable 5/6 (Class I mismatch) or 6/6 HLA-matched related or 10 or
             10 matched unrelated donor.

          -  Adequate cardiac function with an ejection fraction ≥ 35% by echocardiography or
             nuclear cardiography within three months of transplantation

          -  Adequate pulmonary function with corrected DLCO ≥ 40% by pulmonary function testing
             within the past three months of transplantation

          -  Adequate renal function with creatinine clearance ≥ 30 ml/min. as calculated by the
             Cockroft and Gault method.

          -  Adequate hepatic function with AST, ALT, alkaline phosphatase, and total bilirubin no
             more than 3 x ULN unless related to neoplastic disease.

          -  Adequate vascular access, either by pheresis flow catheter or peripheral vein
             intravenous catheter, to perform ECP, should the patient be randomized to ECP.

          -  Patients with prior autologous stem cell transplantation are eligible.

          -  Age 18 to 75 years.

          -  Life expectancy of greater than 3 months.

          -  ECOG performance status of 0, 1, or 2.

          -  Platelet counts ≥ 20,000/microliter, with or without transfusion support, at the time
             of ECP, should the patient be randomized to ECP.

          -  Weight ≥ 40 kg.

          -  Systolic blood pressure ≥ 90 mmHg on the day randomization occurs

          -  Negative pregnancy test. The effects of ECP on the developing human fetus at the
             recommended therapeutic dose are unknown. For this reason, women of childbearing
             potential must agree to use adequate contraception (hormonal or barrier method of
             birth control; abstinence) prior to study entry and for the duration of study
             participation. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately.

          -  Able to receive 600 cGy of total body irradiation. If patient previously treated by
             TBI then must be able to receive 400cGY of total body irradiation.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Hypersensitivity or allergy to 8-methoxypsoralen.

          -  Prior allogeneic stem cell transplantation

          -  HLA-DR mismatch or no worse than one antigen-mismatched unrelated donor.

          -  Patients with acute leukemia or acute lymphocytic leukemia with > 5% circulating
             blasts in peripheral blood or > 5% blasts in bone marrow aspirate and biopsy at the
             time of registration

          -  Patients with chemorefractory non-Hodgkin's lymphoma or Hodgkin's disease or multiple
             myeloma

          -  Diagnosis of myelofibrosis

          -  Patients known to be positive for antibodies to HIC or have evidence for active HIC
             viral replication.

          -  Participation in another clinical trial for prevention of GVHD.

          -  Patient is pregnant or lactating.

          -  Lack adequate vascular access for ECP.

          -  Systolic blood pressure < 90 mmHg at the time of randomization, should the patient be
             randomized to ECP.

          -  Evidence of active, ongoing infection.

          -  Unwilling to comply with all study procedures.

          -  Unable or unwilling to give signed informed consent.