Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) for Older Patients With Hematologic Malignancies
Condition: Blood Cancer; Leukemia
MeSH terms: Hematologic Neoplasms
Intervention: Cyclosporine; Anti-thymocyte globulin (ATG); Mycophenolate mofetil (MMF); Filgrastim; Total Lymphoid Irradiation (TLI)
Intervention description: Starting day -3 at a dose of 5 mg/kg orally twice daily with a target trough level of 350 to 450 ng/mL; 1.5 mg/kg for total dose of 7.5mg/kg, IV starting on day -11 to day -7 before HCT; Begins on day 0 after HCT at a dose of 15 mg/kg. Transplant recipients who received related donor grafts received MMF twice daily and those who received unrelated donor grafts received MMF 3 times daily.; Donors mobilized with 16 µg/kg/day filgrastim.
As needed, myelosuppression in transplant recipients will be managed with subcutaneous filgrastim 5 µg/kg/day; 0.8 Gy/day from day -11 to day -7 (inclusive) from day -4 to day -2 (inclusive) with 2 additional fractions of 0.8 Gy delivered on day -1 for total dose of 8 Gy.
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Lenograstim; Cyclosporins; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 303.0
Sex: All
Minimum age: 50 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      To measure how frequently and to what degree a complication of transplant cell acute graft
      versus host disease (GvHD) occurs.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Any patient with one of the following hematolymphoid malignancies or syndromes in whom
             allogeneic hematopoietic stem cell transplant (HST) is warranted. Specific disease
             categories include:

               -  Indolent advanced stage non-Hodgkin lymphomas

               -  Mantle cell lymphoma

               -  Chronic lymphocytic leukemia

               -  Hodgkin disease (Hodgkin's lymphoma)

               -  Acute leukemias in complete remission

               -  Aplastic anemia

               -  Paroxysmal nocturnal hemoglobinuria

               -  Myelodysplastic or myeloproliferative syndromes.

               -  Other selected malignancies/disorders may also be considered but must be approved
                  by the transplant team and the Principal Investigator.

          -  Age > 50 years, or if < 50 years of age, considered to be at high risk for
             regimen-related toxicity associated with conventional myeloablative transplants due to
             pre-existing medical conditions or prior therapy.

          -  A fully human leukocyte antigen (HLA)-identical sibling or matched unrelated donor is
             available. Potential participants with one antigen mismatched donors can be considered
             but only after discussion with the transplant team and the Principal Investigator.

          -  Participant must be competent to give consent.

        EXCLUSION CRITERIA:

          -  Progressive hematolymphoid malignancies despite conventional therapies, or acute
             leukemias not in complete remission.

          -  Uncontrolled central nervous system (CNS) involvement with disease

          -  Fertile men or women unwilling to use contraceptive techniques during and for 12
             months following treatment

          -  Pregnant

          -  Cardiac ejection fraction < 30%

          -  Uncontrolled cardiac failure

          -  Pulmonary diffusing capacity (DLCO) < 40% predicted

          -  Elevation of bilirubin to > 3 mg/dL

          -  Transaminases > 4 x the upper limit of normal

          -  Creatinine clearance < 50 cc/min (24-hour urine collection)

          -  Karnofsky performance score < 60%

          -  Poorly controlled hypertension on multiple antihypertensives

          -  Documented fungal disease that is progressive despite treatment

          -  HIV-positive. Other viral infections, ie, Hepatitis B- and C- positive, evaluated on a
             case-by-case basis

          -  Psychiatric disorders or psychosocial problems which in the opinion of the primary
             physician or Principal Investigator would place the patient at unacceptable risk from
             this regimen.