Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation
Condition: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Myeloproliferative Disorder; Chronic Lymphocytic Leukemia; B-cell Lymphoma; T-cell Lymphoma; Non Hodgkin Lymphoma; Hodgkin Lymphoma; Chronic Myelomonocytic Leukemia
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Myeloproliferative Disorders
Intervention: Total body irradiation (TBI); Anti-thymocyte globulin (ATG); Tacrolimus; Mycophenolate mofetil (MMF); Total lymphoid irradiation (TLI)
Intervention description: Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning; Given intravenous (IV), Dose 1.5 mg/kg x 5 days; Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV); Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors.; 9 x 120 cGy over 11 days
Intervention MeSH terms: Mycophenolic Acid; Tacrolimus; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate whether addition of a low dose of total body
      irradiation (TBI) to a standard preparation for transplant [total lymphoid irradiation (TLI)
      and anti-thymocyte globulin (ATG)] conditioning will help to augment donor chimerism without
      reducing tolerability of this regimen or increasing the risk of graft-vs-host disease (GVHD)
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Has a human leukocyte antigen (HLA)-matched or single allele mismatched adult sibling
             donor or unrelated donor.

          -  Acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); myeloproliferative
             disease syndrome (MPD)]; chronic lymphocytic leukemia (CLL); B- or T-cell non Hodgkin
             lymphoma (NHL); Hodgkin lymphoma (HL); or chronic myelomonocytic leukemia (CMML),
             suitable for treatment with allogeneic transplant after TLI and ATG reduced intensity
             conditioning.

          -  Considered at high-risk for regimen-related toxicity from fully-ablative transplant
             conditioning (therefore reduced-intensity conditioning is recommended).

          -  Ability to understand and the willingness to sign a written informed consent document.
             Patients must have signed informed consent to participate in the trial.

        EXCLUSION CRITERIA

          -  Uncontrolled bacterial, viral or fungal infection defined as currently taking
             medication and progression of clinical symptoms.

          -  Progressive hemato lymphoid malignancy despite conventional therapy.

          -  Chronic myelogenous leukemia (CML).

          -  Active CNS involvement of the underlying malignancy.

          -  HIV positive

          -  Pregnant or lactating

          -  Prior malignancy (EXCEPTION: diagnosed > 5 years ago without evidence of disease, OR
             treated ≤ 5 years ago but have a greater than 50% chance of life expectancy of ≥ 5
             years for that malignancy).

          -  Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of
             the primary physician would place the patient at an unacceptable risk from transplant.

          -  Left ventricular ejection fraction (LEVF) < 30%, or uncontrolled cardiac failure

          -  Diffusing capacity of lung for carbon monoxide (DLCO) < 40% predicted

          -  Total bilirubin > 3 mg/dL

          -  Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase
             (SGPT) > 4 x upper limit of normal (ULN)

          -  Creatinine > 2 mg/dL and an estimated creatinine clearance < 40 mL/min

          -  Poorly-controlled hypertension despite multiple antihypertensive medications

          -  Karnofsky Performance Status (KPS) < 60%