Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS
Condition: Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic; Lymphoma; Lymphoma, Mantle-cell; Lymphoma, Non-Hodgkin; Hodgkin Disease
MeSH terms: Lymphoma; Leukemia; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoma, Mantle-Cell; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Graft vs Host Disease
Intervention: RFT5-SMPT-dgA; Isolex system
Intervention description: A specific anti-interleukin-2 receptor immunotoxin; CD34 selection/ T cell depletion used this system
Intervention MeSH terms: Interleukin-2; Immunotoxins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Peripheral Blood Stem Cell; Melphalan; Fludarabine; Donor Apheresis; Non-Myeloablative; MDS; Chronic Myeloid Leukemia; CML; Chronic Lymphocytic Leukemia; CLL; Lymphoma; Non-Hodgkin's Lymphoma; Hodgkin's Disease; Mantle Cell Lymphoma; Acute Myelogenous Leukemia (AML); Chronic Myeloid Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Myelodysplasia (MDS); Acute Lymphoblastic Leukemia (ALL); Bone Marrow Transplant

Summary:

      This study will evaluate the safety and effectiveness of stem cell transplantation in which
      the donors T lymphocytes have undergone "selective depletion." Certain patients with cancers
      of the blood undergo transplantation of donated stem cells to generate new and normally
      functioning bone marrow. In addition to producing the new bone marrow, the donor's
      T-lymphocytes also fight any tumor cells that might have remained in the body. This attack on
      tumor cells is called a "graft-versus-leukemia" (GVL) effect. However, another type of
      T-lymphocyte from the donor may cause what is called "graft-versus-host-disease" (GVHD), in
      which the donor cells recognize the patient's cells as foreign and mount an immune response
      to reject them. Selective depletion is a technique that was developed to remove the
      T-lymphocytes that cause harmful GVHD, while keeping those that produce the desirable GVL
      effect.
    

Eligibility criteria:

        - INCLUSION CRITERIA: PATIENT

          -  Ages 50-75 years

          -  Relapsed CML in chronic or accelerated phase after therapy with STI-571 (Gleevec)

          -  Acute lymphoblastic leukemia (ALL), all patients in complete or partial remission.
             Exceptions: T cell ALL

          -  Acute myelogenous leukemia (AML): AML in first complete or partial remission including
             AML secondary to chemotherapy or prior hematological disease such as myelodysplastic
             syndrome, and myeloproliferative disorder.

          -  Myelodysplastic syndromes: (1) refractory anemia with excess of blasts (RAEB), (2)
             refractory anemia with excess blasts in transformation (RAEBT), (3) MDS with poor risk
             cytogenetics defined by a complex karyotype (greater than or equal to three anomalies)
             or chromosome 7 abnormalities, (4) secondary MDS after prior cytotoxic or radiation
             therapy, or (5) chronic myelomonocytic leukemia (CMML)

          -  Chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia, refractory to
             nucleoside analog therapy, with either progressive bulky disease or anemia (less than
             10 g/dl) or thrombocytopenia (less than 100,000/microliter) not due to recent
             chemotherapy

          -  Mantle cell lymphoma

          -  Relapsed intermediate- or high-grade non-Hodgkin's lymphoma: (1) post autologous
             marrow or PBSC transplant, or (2) chemorefractory relapse. Exceptions: T cell NHL

          -  Relapse Hodgkin's disease: (1) post autologous marrow or PBSC transplant, or (2)
             chemorefractory relapse

          -  Low-grade follicular or small lymphocytic lymphoma: (1) relapsed following
             conventional chemotherapy, (2) relapsed following autologous marrow or PBSC
             transplant, or (3) chemoresistant disease

          -  Life expectancy greater than 3 months

          -  Ability to comprehend the investigational nature of the study and provide informed
             consent

          -  Availability of an HLA-identical family donor, 18 to 75 years old

          -  INCLUSION CRITERIA:

        DONOR

          -  HLA identical family donor, 18 to 75 years old

          -  Fit to receive G-CSF and give peripheral blood stem cells (normal blood count,
             normotensive, no history of stroke, no history of severe heart disease)

          -  Ability to comprehend the investigational nature of the study and provide informed
             consent

          -  EXCLUSION CRITERIA:

        RECIPIENT

          -  Pregnant or lactating

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 3 or more

          -  Major anticipated illness or organ failure incompatible with survival from PBSC
             transplant

          -  Diffusion Capacity fir carbon monoxide (DLCO) less than 60% predicted

          -  Left ventricular ejection fraction less than 40%, or any angina.

          -  Absolute lymphocyte count less than 300/mm(3)

          -  Serum creatinine greater than 2.5 mg/dl

          -  Serum bilirubin greater than 4 mg/dl, transaminases greater than 5x upper limit of
             normal

          -  HIV positive

          -  Other malignant diseases liable to relapse or progress within 2 years

          -  EXCLUSION CRITERIA:

        DONOR

          -  Pregnant or lactating

          -  HIV positive. Donors who are positive for Hepatitis B Virus, Hepatitis C Virus or
             human t-cell lymphoma virus (HTLV) will be used at the discretion of the investigator
             and with appropriate consent of the recipient

          -  Donor unfit to receive G-CSF and undergo apheresis (uncontrolled hypertension, history
             of heart failure or unstable angina, platelet count less than 90,000/cu mm)