HLA-Compatible Related or Unrelated Donors With CD34+ Enriched, T-cell Depleted Peripheral Blood Stem Cells Isolated by the CliniMACS System in the Treatment of Patients With Hematologic Malignancies
Condition: Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Multiple Myeloma
MeSH terms: Leukemia; Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Hematologic Neoplasms; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Intervention: total body irradiation; Thiotepa; Cyclophosphamide; Busulfan; Melphalan; Fludarabine; Clofarabine; (CliniMACS) T-cell depleted PBSC Transplant
Intervention description: dose of 1375-1500 cGy; 5 mg/kg/day x 2 or 10 mg/kg/day x 1; 60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated).; 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics; 70mg/m2/day x 2; 25mg/m2/ day x 5; 20mg/m2/ day x 5 (or, for children <18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval)
Intervention MeSH terms: Cyclophosphamide; Melphalan; Busulfan; Thiotepa; Fludarabine; Clofarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 422.0
Sex: All
Maximum age: 69 Years
Healthy volunteers: No
Keywords: Leukemia; Multiple Myeloma; radiation; Thiotepa; cyclophosphamide; fludarabine; Clofarabine; CliniMACS device; GCSF; 10-050

Summary:

      The purpose of this study is to find out the effects of using a system called CliniMACS to
      remove Tcells from blood stem cells. Removing T-cells may help stop a side effect called
      Graft-Versus-Host Disease (GVHD). Some studies have been done with CliniMACS, but the Food
      and Drug Administration (FDA) has not yet approved it.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Malignant conditions or other life threatening disorders correctable by transplant for
             which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell
             transplantation is indicated such as:

          -  AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic
             features (i.e. t 8;21, t15;17, inv 16).

          -  Secondary AML in 1st remission

          -  AML in 1st relapse or > than or = to 2nd remission

          -  ALL/CLL in 1st remission clinical or molecular features indicating a high risk for
             relapse; or ALL/CLL > than or = to 2nd remission

          -  CML failing to respond to or not tolerating Imatinib or dasatinib in first chronic
             phase of disease; CML in accelerated phase second chronic phase or in CR after
             accelerated phase or blast crisis.

          -  Non-Hodgkins lymphoma with chemoresponsive disease in any of the following categories:

               1. intermediate or high grade lymphomas who have failed to achieve a first CR or
                  have relapsed following a 1st remission who are not candidates for autologous
                  transplants.

               2. any NHL in remission which is considered not curable with chemotherapy alone and
                  not eligible/appropriate for autologous transplant.

          -  Myelodysplastic syndrome (MDS): RA//RARS/RCMD with high risk cytogenetic features or
             transfusion dependence as well as RAEB-1 and RAEB-2 and Acute myelogenous leukemia
             (AML) evolved from MDS, who are not eligible for transplantation and/or unable to
             enroll onto protocol IRB 08-008.

          -  Chronic myelomonocytic leukemia: CMML-1 and CMML-2.

          -  Multiple Myeloma with disease in the following categories:

               1. Patients with relapsed multiple myeloma following autologous stem cell
                  transplantation who have achieved at least partial response following additional
                  chemotherapy.

               2. Patients with high risk cytogenetics at diagnosis must have achieved a partial
                  response following autologous stem cell transplantation. Patients must have
                  complex karyotype, del17p, t4;14 and/or t14;16 by FISH and/or del13 by
                  karyotyping.

          -  Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell
             depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory
             aplastic anemia or congenital cytopenias; non-SCID lethal genetic immunodeficiencies
             such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, or ALPS, as well as
             refractory autoimmune cytopenias, PNH, metabolic storage diseases or heavily
             transfused congenital hemoglobinopathies).

          -  Accrual to each treatment arm will include up to 30 standard risk and 30 poor risk
             patients (60 patients/treatment arm) except for Regimen D, which will include 30
             patients/treatment arm, all of which will be poor risk by virtue of risks of relapse
             and/or transplant related mortality.

          -  Standard risk patients will include eligible patients, as defined above, who are
             receiving transplants as treatment for MDS in RA//RARS/RCMD, AML in 1st or 2nd
             remission, ALL in 1st CR, NHL in 1st remission, MM in 1st remission, Very Good Partial
             Response, or 1st Partial Response or CML in the first chronic phase or 1st remission.

          -  All other patients, including those with treatment related malignancies and/or those
             who have AML derived from MDS, will have received extensive prior chemo/radiotherapy
             and, therefore, will be considered to be at poor risk of conditioning and transplant
             related morbidities, and potentially transplant related mortality. Patients with life
             threatening non-malignant genetic and acquired disorders will also, by virtue of their
             history of, optional transfusions and/or infection be considered poor risk. Stopping
             rules for non-relapse related mortality in these heavily treated patients are,
             therefore, slightly less stringent than patients in the poor risk transplant groups.
             Stopping rules for the principal endpoints of graft failure and GvHD are the same for
             all groups.

        The following inclusion criteria are also required:

          -  Patient's age includes from birth on to < 70 years old.

          -  Patients may be of either gender or any ethnic background.

          -  Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > or =
             to 70%

          -  Patients must have adequate organ function measured by:

        Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > or = to 50% and must
        improve with exercise.

        Hepatic: < 3x ULN AST and ≤ to 1.5 total serum bilirubin, unless there is congenital benign
        hyperbilirubinemia or if the hyperbilirubinemia is directly caused by the disease in which
        the patient is receiving a transplant (e.g. AML Chloroma obstructing the biliary tree).
        Patients with higher bilirubin levels due to causes other than active liver disease are
        also eligible with PI approval e.g. patients with PNH, Gilbert's disease or other hemolytic
        disorders.

        Renal: serum creatinine < than or = to 1.2 mg/dl or if serum creatinine is outside the
        normal range, then CrCl > 40 ml/min (measured or calculated/estimated) Pulmonary:
        asymptomatic or if symptomatic, DLCO > or = to 50% of predicted (corrected for hemoglobin)

          -  Each patient must be willing to participate as a research subject and must sign an
             informed consent form.

        Exclusion Criteria:

          -  Female patients who are pregnant or breast-feeding

          -  Active viral, bacterial or fungal infection

          -  Patient seropositive for HIV-I/II; HTLV -I/II

          -  Presence of leukemia in the CNS.

        Donor Inclusion Criteria:

          -  Each donor must meet criteria outlined by institutional guidelines

          -  Donor should agree to undergo general anesthesia and bone marrow harvest collection if
             PBSC yield is inadequate or otherwise not transplantable for whatever reason.

        Donor Exclusion Criteria

          -  If donors do not meet institutional guidelines, exclusion will be considered.