T-Cell Depletion, Donor Hematopoietic Stem Cell Transplant (HSCT), and T-Cell Infusions in Treating Patients With Hematologic Cancer or Other Diseases
Condition: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Malignant Plasma Cell Neoplasms; Myelodysplastic Syndromes; Precancerous/Nonmalignant Condition; Secondary Myelofibrosis
MeSH terms: Multiple Myeloma; Preleukemia; Neoplasms, Plasma Cell; Plasmacytoma; Precancerous Conditions; Myelodysplastic Syndromes; Myeloproliferative Disorders
Intervention: peripheral blood lymphocyte therapy; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; total-body irradiation (TBI)
Intervention description: T-cell depletion will be accomplished using CD34 selection with the Baxter Isolex 300i v. 2.5 device. The desirable T-cell dose will be >0.5 x 105 but <1.0 x 105 CD3+ cells per kg. The targeted CD34 cell dose will be >2 x 106 cells/kg.; Allogeneic Hematopoietic Stem Cell Transplantation; Peripheral blood stem cell transplantation; Treatment will be delivered using 6MV photons twice daily for 3 days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Allogeneic Hematopoietic Stem Cell Transplantation
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Adult leukemia; lymphoma; myelodysplastic syndromes; plasma cell disorders

Summary:

      RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood
      stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the
      patient's immune system from rejecting the donor's stem cells. When stem cells from a donor
      are infused into the patient they may help the patient's bone marrow make stem cells, red
      blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor
      can make an immune response against the body's normal cells. Removing the T cells from the
      donor cells before transplant may stop this from happening. Giving an infusion of the donor's
      T cells (donor lymphocyte infusion) after the transplant may help destroy any remaining
      cancer cells (graft-versus-tumor effect).

      PURPOSE: This phase II trial is studying T-cell depletion in donor stem cell transplant
      followed by delayed T cell infusions in treating patients with hematologic cancer or other
      disease.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of any of the following hematologic cancers or other diseases:

               -  Acute myelogenous leukemia

                    -  Relapsed or refractory disease with poor-risk cytogenetics

               -  Acute lymphoblastic leukemia

                    -  Relapsed or refractory disease with poor-risk cytogenetics

               -  Chronic myelogenous leukemia

                    -  Persistent disease after at least 6 months of treatment with imatinib
                       mesylate (Gleevec)

               -  Myelodysplasia, meeting 1 of the following criteria:

                    -  French-American-British Classification of refractory anemia with excess
                       blasts (RAEB) or RAEB with transformation

                    -  International Prognostic Scoring System score > 2

               -  Lymphoid malignancies, including non-Hodgkin lymphoma, Hodgkin disease, chronic
                  lymphocytic leukemia, and prolymphocytic leukemia

                    -  Relapsed or refractory disease after at least 1 prior therapy

               -  Myelofibrosis

                    -  Transfusion dependent (RBC's, platelets, or both)

               -  Paroxysmal nocturnal hemoglobinuria (transfusion dependent)

               -  Myeloproliferative disorder

               -  Eosinophilic leukemia

               -  Severe aplastic anemia

                    -  Corrected reticulocyte count < 1%

                    -  Platelet count < 30,000/mm³ (untransfused)

                    -  Bone marrow biopsy with < 15% cellularity

               -  Plasma cell leukemia

          -  No essential thrombocytopenia or polycythemia vera

          -  No matched related donor available

          -  Must have an 8/8 or 7/8 serologic HLA matched unrelated donor available

        PATIENT CHARACTERISTICS:

          -  Cardiac ejection fraction ≥ 45% (if < 45%, then cardiac consult required)

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  FEV_1 and DLCO ≥ 45% predicted

          -  Creatinine < 2.0 mg/dL

          -  Bilirubin < 2.0 mg/dL

          -  HIV negative

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior allogeneic bone marrow transplantation

          -  No concurrent administration of steroids with T-cell add-backs

        INCLUSION CRITERIA:

          -  Patient actual weight must not be greater than 1.5x their ideal body weight

          -  Cardiac ejection fraction >45%. If less than 45%, a Cardiac consult will be obtained.

          -  A suitably matched unrelated donor that is at least a 7 out of 8 HLA serologic match.

          -  Patient is not pregnant.

          -  FEV 1 and DLCO > 45% predicted on pulmonary function testing.

          -  Serum creatinine <2.0 mg/dl, serum bilirubin <2.0 mg/dl.

          -  Patient and donor are HIV negative.

          -  Diagnosis of one of the following diseases

          -  Acute myelogenous leukemia

          -  Relapsed disease,

          -  Refractory disease, or

          -  With poor-risk cytogenetics

          -  Acute lymphoblastic leukemia

          -  Relapsed disease,

          -  Refractory disease, or

          -  With poor-risk cytogenetics

          -  Chronic myelogenous leukemia

          -  Persistent disease after at least 6 months of treatment with Imatinib Mesylate
             (Gleevec)

          -  Myelodysplasia

          -  FAB Classification of RAEB or RAEB-T -Or-

          -  IPSS score >2

          -  Lymphoid malignancies, including non-Hodgkin's lymphoma, Hodgkin's disease, chronic
             lymphocytic leukemia and prolymphocytic leukemia

          -  Relapsed or refractory disease after at least 1 prior therapy

          -  Myelofibrosis

          -  Transfusion dependence (RBC's, platelets, or both)

          -  Paroxysmal Nocturnal Hemoglobinuria (PNH)

          -  Transfusion dependent

          -  Myeloproliferative Disorder

          -  Eosinophilic Leukemia

          -  Severe aplastic anemia (<1% corrected reticulocyte count, <30,000 untransfused
             platelet count, bone marrow biopsy with <15% cellularity)

          -  Plasma cell leukemia

          -  Patients with ET or PV will not be candidates unless their disease has transformed to
             end stage myelofibrosis or acute leukemia, for which eligibility criteria for
             myelofibrosis or acute leukemia would apply.

          -  Patient must signed written informed consent.

        EXCLUSION CRITERIA:

          -  Inability to give informed consent

          -  Absence of any of the above mentioned medical conditions

          -  Availability of matched-related donor

          -  History of prior allogeneic BMT