Methods to Enhance the Safety and Effectiveness of Stem Cell Transplants
Condition: Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome
MeSH terms: Leukemia; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Syndrome
Intervention: Miltenyi reagent system; Fludarabine; Cyclosporine; Cyclophosphamide; FILGRASTIM (G-CSF)
Intervention description: Miltenyi Clinimax CD34 Reagent System for CD34 selection and delayed T cell depletion add back; Therapeutic; Therapeutic; Therapeutic; An HLA 6/6 identical family member will be co-enrolled into this study as a stem cell donor. Stem cell Donors will receive G-CSF for stem cell mobilization. The stem cell collection aspect of this protocol is not investigational.
Intervention MeSH terms: Cyclosporine; Cyclophosphamide; Fludarabine; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 116.0
Sex: All
Minimum age: 10 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Chronic Myelogenous Leukemia (CML); Acute Myelogenous Leukemia (AML); Chronic Lymphocytic Leukemia (CLL); Acute Lymphoblastic Leukemia (ALL); Myelodysplastic Syndrome (MDS); Leukemia; Chronic Myelogenous Leukemia; CML; Acute Myeloid Leukemia; AML; Chronic Lymphocytic Leukemia; CLL; Acute Lymphoblastic Leukemia; ALL; Myelodysplasia Syndrome

Summary:

      Bone marrow stem cell transplants (otherwise called bone marrow transplants) from healthy
      donors are sometimes the only means of curing hematological malignant diseases such as acute
      and chronic leukemias, myelodysplastic syndrome, myeloproliferative diseases and lymphomas.
      Before transplant the patient receives chemotherapy and radiation treatment to reduce the
      malignancy to low levels and to prevent rejection of the transplant. The transplant restores
      the blood counts to normal and replaces the patients immunity with that of the donor. The
      donors immune cells increase the effect of the transplant by attacking remaining malignant
      cells. Donor immune cells (especially those called T lymphocytes) also attack healthy
      non-cancerous cells and tissues of the recipient causing "graft-versus-host-disease" (GVHD).
      Strong GVHD reactions occurring within weeks after the transplant can be life-threatening .
      In this study we remove most of the T lymphocytes from the transplant to minimize the risk of
      GVHD. However to improve immunity against residual malignant cells and boost immunity to
      infections, donor T cells (stored frozen at time of transplant) are given back around 90 days
      after the transplant when they have a reduced risk of causing serious GVHD.

      Any patient between 10 and 75 years of age with acute or chronic leukemia, myelodysplastic
      syndrome, myeloproliferative syndromes or lymphoma, who have a family member who is a
      suitable stem cell donor may be eligible for this study. Candidates are screened with a
      medical history and various tests and examinations.
    

Eligibility criteria:

        INCLUSION CRITERIA - RECIPIENT:

          -  Ages 10-75 years inclusive

          -  Chronic myelogenous leukemia (CML):

          -  Subjects under the age of 21 in chronic phase

          -  Subjects ages 10-75 in chronic phase who have failed treatment with imatinib, have
             intolerance to imatinib, or who did not receive imatinib at therapeutic doses within
             the first 12 months from diagnosis.

          -  Subjects ages 10-75 in accelerated phase or blast transformation.

          -  Acute lymphoblastic leukemia (ALL): any of these categories: ALL in first remission
             with high-risk features (presenting leukocyte count greater than 100,000/cu mm,
             Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia) All second or subsequent
             remissions, primary induction failure, partially responding or untreated relapse.

          -  Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk
             karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21). All AML in second or
             subsequent remission, primary induction failure and resistant relapse

          -  Myelodysplastic syndromes (MDS): any of these categories - refractory anemia with
             transfusion dependence, refractory anemia with excess of blasts, transformation to
             acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative
             syndromes

          -  Myeloproliferative disorders including atypical (Ph negative) chronic myeloid and
             neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential
             thrombocythemia in transformation to acute leukemia or with progressive transfusion
             requirements or pancytopenia.

          -  Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky
             progressive disease or with thrombocytopenia (less than or equal to 100,000 /microl)
             or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.

          -  Non-Hodgkins lymphoma including Mantle cell lymphoma relapsing or refractory to
             standard of care treatments

          -  Multiple myeloma, Waldenstrom's macroglobulinemia, unresponsive or relapsed following
             standard of care treatments.

          -  HLA identical (6/6) related donor

          -  For adults: Ability to comprehend the investigational nature of the study and provide
             informed consent. For minors: written informed consent from one parent or guardian.
             Informed oral consent from minors: the process will be explained to the minor on a
             level of complexity appropriate for their age and ability to comprehend.

        EXCLUSION CRITERIA - RECIPIENT:

          -  Estimated probability of surviving less than three months

          -  Major anticipated illness or organ failure incompatible with survival from transplant

          -  Severe psychiatric illness. Mental deficiency sufficiently severe as to make
             compliance with the transplant treatment unlikely and making informed consent
             impossible.

          -  Positive pregnancy test for women of childbearing age.

          -  HIV positive

          -  Diffusion Capacity of Lung for Carbon Monoxide (DLCO) adjusted for ventilation and
             hemoglobin less than 65 percent predicted

          -  Left ventricular ejection fraction less than 40 percent

          -  Aspartate Aminotransferase (AST)/Serum Glutamate Oxaloacetate Transaminase (SGOT)
             greater than 10 times upper limit of normal (ULN) (CTCAE grade IV v3.0)

          -  Bilirubin greater than 5 times upper limit of normal (ULN) (CTCAE grade IV v3.0)

          -  Creatinine greater than 4.5 times upper limit of normal (ULN) (CTCAE grade IV v 3.0)

          -  Prior allogeneic stem cell transplantation.

        INCLUSION CRITERIA - DONOR:

          -  Related donor, HLA identical (6/6) with recipient

          -  Weight greater than or equal to 18 kg

          -  Age greater than or equal to 2 or less than or equal to 80 years old

          -  For adults: Ability to comprehend the investigational nature of the study and provide
             informed consent. For minors: Written informed consent from one parent or guardian and
             informed assent: The process will be explained to the minor on a level of complexity
             appropriate for their age and ability to comprehend.

        EXCLUSION CRITERIA - DONOR:

          -  Pregnant. Lactating donors permitted provide breast milk is discarded during the days
             that G-CSF is given

          -  Unfit to receive filgrastim (G-CSF) and undergo apheresis (abnormal blood counts,
             history of stroke, uncontrolled hypertension)

          -  Sickling hemoglobinopathies including HbSS, HbAS, HbSC

          -  HIV positive donors who are positive for hepatitis B (HBV), hepatitis C (HCV) or human
             T-cell lymphotropic virus (HTLV-I/II) will be used at the discretion of the
             investigator following counseling and approval from the recipient

          -  Severe psychiatric illness. Mental deficiency sufficiently severe as to make
             compliance with the BMT treatment unlikely, and making informed consent impossible