Allogeneic Transplantation From Related Haploidentical Donors
Condition: Blood Cancer; Leukemia; Graft Versus Host Disease; Malignancy; CLL; NHL; Hodgkin's Disease; MDS
MeSH terms: Neoplasms; Hodgkin Disease; Hematologic Neoplasms; Graft vs Host Disease
Intervention: non-myeloablative hematopoietic cell transplantation; Anti-Thymocyte Globulin; Cyclosporine; Mycophenolate Mofetil; G-CSF; Solumedrol; Acetaminophen; Diphenydramine; Hydrocortisone
Intervention description: TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil.; 1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes.; 6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin).; 15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively which blocks the de nobo synthesis of guanosine required for DNA synthesis and has an effect on T and B cells.; 16 mg/kg, SQ Growth factor used to make bone marrow produce more blood cells; 1.0 mg/kg IV 2 hours prior to ATG Used to treat severe inflamation; 650 mg PO, 30 minutes prior to infusion Pain reliever; 50 mg IV, 30 minutes prior to infusion Used to relieve allergy symptoms; 100 mg IV, 1 hour prior to infusion Used to relieve itching, redness and swelling of the skin
Intervention MeSH terms: Acetaminophen; Cyclosporine; Mycophenolic Acid; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cyclosporins; Antilymphocyte Serum; Lenograstim; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 12 Months
Healthy volunteers: No

Summary:

      The purpose of the study is to evaluate the feasibility and safety of transplanting CD34+
      selected hematopoietic cells from a haploidentical related donor following a nonmyeloablative
      regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 50 years with hematologic malignancies treatable by a mixed chimera allogeneic
             HCT.

          -  For patients ≤ 50 years of age with hematologic malignacies treatable with mixed
             chimera HCT who because of pre-exisiting medical conditions or prior therapy are
             considered to be at high risk for regimen-related toxicity associated with
             conventional transplants.

          -  Indolent advanced stage NHL, CLL, HD - Must have received and failed front-line
             therapy.

          -  Multiple myeloma (Stage II or III) - Must have received prior chemotherapy.
             Consolidation after prior autografting is permitted.

          -  AML/ALL - Must be in complete hematologic remission and have received cytotoxic
             chemotherapy at some stage before transplant. Patients with molecular or cytogenetic
             relapse will be accepted providing a donor is available. Patients with persistent or
             refractory disease will be considered on a case by case basis and transplants must be
             approved by the principal investigator.

          -  CML - Patients will be accepted in chronic or accelerated phase. Patients who have
             received prior autografts after high dose therapy or have undergone intensive
             chemotherapy for either peripheral blood stem cell mobilization or treatment of
             advanced CML may be enrolled provided they are in CR, chronic phase or accelerated
             phase.

          -  MDS - All patients with MDS will be eligible for this protocol, however, those
             patients with >10% blasts will require chemotherapy to reduce the blast % to < 10%.

          -  SAA - Patients with severe aplastic anemia who have failed front line therapy.

          -  A fully HLA-identical sibling donor is not available.

          -  A matched unrelated donor has not been identified.

          -  A haploidentical related donor is available who is in good health and does not have
             contraindications to donation.

        Exclusion Criteria:

          -  Patients with rapidly progressive intermediate or high grade NHL

          -  Uncontrolled CNS involvement with disease

          -  Fertile men

          -  Women unwilling to use contraceptive techniques during and for 12 months following
             treatment

          -  Females who are pregnant

          -  Cardiac function: ejection fraction < 30% or cardiac failure requiring therapy

          -  Pulmonary: DLCO < 40% predicted and/or receiving supplementary continuous oxygen

          -  Liver function abnormalities: elevation of bilirubin to > 4 mg/dl and/or transaminases
             > 3x the upper limit of normal. If hyperbilirubinemai is due to a known cause that
             will not increase the risks of transplant, than this upper limit may be exceeded.

          -  Renal: creatinine clearance < 50 cc/min (24 hour urine collection)

          -  Karnofsky performance score < 60%

          -  Patients with poorly controlled hypertension.

          -  Documented fungal disease that persists despite treatment

          -  HIV positive patients.

          -  Hepatitis B and C positive patients will be 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.