Stem Cell Transplantation for Patients With Cancers of the Blood
Condition: CML (Chronic Myelogenous Leukemia); CLL (Chronic Lymphocytic Leukemia); AML (Acute Myelogenous Leukemia); Acute Lymphocytic Leukemia; MDS (Myelodysplastic Syndrome)
MeSH terms: Leukemia; Preleukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes
Intervention: Miltenyi system
Intervention description: Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Evaluation of selective depletion of alloreactive T cells to prevent graft vs host disease
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: CML (Chronic Myelogenous Leukemia); CLL (Chronic Lymphocytic Leukemia); AML (Acute Myelogenous Leukemia); Leukemia; Chronic Lymphocytic Leukemia; CLL; Chronic Myelogenous Leukemia; CML; Acute Myelogenous Leukemia; AML; Acute B-Lymphoblastic Leukemia; ALL; Myelodysplastic Syndrome; MDS

Summary:

      This study will try to improve the safety and effectiveness of stem cell transplant
      procedures in patients with cancers of the blood. It will use a special machine to separate
      immune cells (T cells) from the blood of both the donor and the patient and will use
      photodepletion, a laboratory procedure that selectively kills cancer cells exposed to light.
      These special procedures may reduce the risk of graft-versus-host-disease (GVHD), a serious
      complication of stem cell transplants in which the donor's immune cells destroy the patient's
      healthy tissues, and at the same time may permit a greater graft-versus-leukemia effect, in
      which the donated cells fight any residual tumor cells that might remain in the body.

      Patients between 18 and 75 years of age with a life-threatening disease of the bone marrow
      (acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome) may be
      eligible for this study. Candidates must have a family member who is a suitable tissue match.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        Recipient Criteria:

          -  Diagnosed with one of the following hematological conditions:

          -  Chronic myelogenous leukemia (CML): 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; accelerated phase or blast
             transformation.

          -  Acute B-lymphoblastic leukemia (B-ALL): any of these categories: B-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-Hodgkin's lymphoma including Mantle cell lymphoma relapsing or refractory to
             standard of care treatments.

          -  Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following
             standard of care treatments.

          -  Ages 18-75 years inclusive.

          -  HLA identical (6/6) related donor.

          -  Ability to comprehend the investigational nature of the study and provide informed
             consent.

        Donor Criteria:

          -  Related 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:

        Recipient Criteria (any of the following):

          -  Malignant cells expressing a T cell phenotype (in particular T-ALL and T cell NHL).

          -  DLCO less than 65 percent predicted.

          -  Left ventricular ejection fraction less than 40 percent (evaluated by ECHO) or less
             than 30 percent (evaluated by MUGA).

          -  AST/SGOT greater than 10 times ULN (CTCAE grade IV v3.0).

          -  Bilirubin greater than 5 times ULN (CTCAE grade IV v3.0).

          -  Creatinine greater than 4.5 times ULN (CTCAE grade IV v 3.0).

          -  HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or
             human T-cell lymphotropic virus (HTLV-1/II) are not excluded from participation).

          -  Positive pregnancy test for women of childbearing age.

          -  Prior allogeneic stem cell transplantation.

          -  Estimated probability of surviving less than three months.

          -  Major anticipated illness or organ failure incompatible with survival from transplant.

          -  Severe psychiatric illness or mental deficiency sufficiently severe as to make
             compliance with the transplant treatment unlikely and informed consent impossible.

        Donor Criteria (any of the following):

          -  Pregnant or lactating.

          -  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 or mental deficiency sufficiently severe as to make
             compliance with the donation of stem cells unlikely and informed consent impossible.