Safety and Efficacy of Pentostatin and Low Dose TBI With Allogenic Peripheral Blood Stem Cell Transplant
Condition: Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Myelodysplastic Syndromes; Multiple Myeloma; Non-Hodgkins Lymphoma; Hodgkins Disease; Peripheral T-cell Lymphoma
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Lymphoma, T-Cell, Peripheral; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Hodgkin Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes
Intervention: Pentostatin; Total-body irradiation (TBI); Cyclosporine A (CsA); Mycophenolate Mofetil (MMF); G-CSF
Intervention description: 4 mg/m^2 intravenous(IV)once a day(QD)x3days (days -10, -9, -8); TBI will consist of 2.0 GY at 8-12cGy/min via 6MV photons delivered AP/PA fields, without lung blocks or via lateral fields with lucite compensator along the head and neck region. TLD (thermal luminescent dosimetry) will be used to verify dose uniformity. TBI will be given on day -1.; CsA will be given at 2.0 mg/kg intravenous (IV) Q 12hrs on days -1,0,and+1 (total 6 doses) then converted to oral at 2 mg/kg by mouth (PO) twice a day (BID) until day+80, then tapered 10% per week over approximately 3 months if no GVHD for related donor transplants. For unrelated CsA will be given at same dose and schedule until day+100 then tapered by 10% per week if no GVHD; MMF 15 mg/kg by mouth twice a day (PO BID) will be given from day 0-27 then stopped without tapering for related donor transplants. For unrelated donor transplants MMF will be given at same dose until day+40 then tapered over 2months. in absence of GVHD. Doses will be rounded to nearest 250 mg.; 10 mcg/kg/day subcutaneously for at least 4 consecutive days.
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Pentostatin; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 76.0
Sex: All
Minimum age: 19 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is a continuation of a pilot study which is now regarded as a phase II trial with a plan
      to enroll an additional 40 patients (20 related and 20 unrelated donor transplants) with
      hematological malignancy assessing the safety and efficacy of a minimally myelosuppressive
      regimen with pentostatin and low-dose total body irradiation (TBI) followed by allogeneic
      peripheral blood stem cell transplantation (alloPSCT).
    

Eligibility criteria:

        Inclusion Criteria:

        Age 19-75 years

          1. Patients who relapse after autologous stem cell transplantation.

          2. Patients who are candidates for an autologous or conventional allogeneic stem cell
             transplantation from a disease standpoint but who do not qualify functionally (from
             the point of view of organ function, or performance status) for a myeloablative
             protocol.

          3. Any patient, where in the opinion of the primary treating oncologist, nonmyleoablative
             therapy would be the treatment option in the best patients interest providing the
             patient fits all other eligibility criteria for this protocol.

        Identification of a matched related or unrelated stem cell donor

        Diseases:

        Acute myelogenous leukemia first complete remission with high-risk cytogenetics>second
        complete remission minimal residual disease (<10% blasts*). Acute lymphocytic leukemia
        first complete remission with high-risk cytogenetics >second complete remission minimal
        residual disease (<10% blasts*). Chronic myelogenous leukemia first chronic phase,
        accelerated phase (<10% blasts*)blast phase with minimal residual disease (<10%
        blasts*)second chronic phase. Chronic lymphocytic leukemia recurrence after the front line
        regimen (related donor transplant), chemorefractory disease (unrelated donor
        transplant),T-CLL in partial remission or any minimal residual disease. Myelodysplastic
        syndromes refractory anemia with or without ringed sideroblasts,RAEB, RAEB-T, and CMML (<
        than 10% blasts*). *both in peripheral blood and bone marrow

        Multiple myeloma - after receiving at least one regimen of prior chemotherapy

        Non-Hodgkin's Lymphomas:

        Small Lympho(plasma)cytic Lymphoma (B-SLL, B-LPL): recurrence after a front line regimen
        (related donor transplant), or chemorefractory disease (related or unrelated donor
        transplant). Follicular Low-Grade Lymphoma, Marginal Zone Lymphomas (splenic, nodal, or
        extranodal/MALT type): chemorefractory disease or > 2 prior regimens. Mantle Cell Lymphoma:
        first complete or partial remission, refractory disease, or failed prior ASCT. Diffuse
        Large B-cell Lymphoma, Follicular Large cell Lymphoma, Peripheral T-cell Lymphoma,
        Anaplastic Large Cell Lymphoma: refractory disease, or failed prior ASCT. Burkitt or Acute
        Lymphoblastic Lymphomas: high-risk disease in remission, chemosensitive persistent or
        recurrent disease. Cutaneous T-cell Lymphomas: (Mycosis Fungoides, Sezary Syndrome):
        chemorefractory disease of > 2 prior regimens

        Hodgkins Disease: refractory or persistent disease and not candidate for ASCT, or failed
        prior ASCT.

        Peripheral T-cell Lymphoma

        Exclusion Criteria:

          -  Age > 75 years and < 19 years

          -  progressive disease within 8 weeks of prior therapy or within 12 weeks after prior
             autologous stem cell transplantation

          -  Active CNS malignancy (patients with known positive CSF cytology or parenchymal
             lesions visible by CT or MRI)

          -  Fertile men or women unwilling to use appropriate contraceptive techniques during and
             for 12 months following treatment

          -  Females who are pregnant

          -  Patients who are HIV seropositive

          -  Active uncontrolled infection or immediate life-threatening condition at the time of
             enrollment

          -  Significant Organ dysfunction:

               1. Calculated Creatinine Clearance <55ml/min

               2. cardiac ejection fraction <40%, NYHA class II or greater cardiac disease.

               3. DLCO < 40% , FEV1/FVC ratio <50% predicted, or receiving supplementary continuous
                  oxygen

               4. total bilirubin > 2x upper limit of normal (unless due to Gilberts disease or
                  malignancy), ALT and AST 4x the upper limit of normal

          -  Karnofsky score <60%

          -  Patients with uncontrolled medical illnesses (e.g., uncontrolled systemic
             hypertension, diabetes)

        Donor Inclusion Criteria:

          -  HLA genotypically matched relative

          -  siblings or first-degree relatives matched at HLA-A, B, or DR loci (6 antigen match)
             are acceptable donors

          -  HLA matched unrelated volunteer donor

          -  unrelated donor matched at HLA-A, B, or DR loci (6 antigen match) are acceptable
             donors

          -  One antigen mismatch related or unrelated donor will also be acceptable, molecular
             typing needs to be used at each H LA-A, B, or DR loci in case of mismatched unrelated
             donor.

        Donor Exclusion Criteria:

          -  Identical twin

          -  Pregnancy

          -  HIV positive

          -  Serious Allergy to G-CSF

          -  Current serious systemic illness

          -  Failure to meet the UNMC or NMDP criteria for donors