Study of Low-Intensity Conditioning for Allogeneic Stem Cell Transplant
Condition: Multiple Myeloma; Lymphocytic Leukemia, Chronic; Lymphoma, Low-Grade
MeSH terms: Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin
Intervention: Reduced intensity conditioning; Rapid immunosuppressive taper; Prophylactic donor leukocyte infusions
Intervention description: Busulfan and Fludarabine regimen; Taper of Tacrolimus, Methotrexate and Mycophenolate Mofetil; If the patient has GVHD overall grade 0-1 or skin grade 1 on day +100, then 5 x 107 CD3+ cells/kg recipient weight are given.
Intervention MeSH terms: Immunosuppressive Agents
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether a reduced intensity conditioning regimen
      for stem cell transplant with donor cells will allow the donor cells to be effective without
      causing health problems.
    

Eligibility criteria:

        Patient Inclusion Criteria:

        To be eligible a patient MUST meet at least one of the next 4 criteria

          -  Any patient aged 55 years or older with a hematological malignancy for which
             allogeneic transplant is considered an appropriate treatment, AND/OR

          -  Any patient, regardless of age, with a hematologic malignancy for which allogeneic
             transplant is considered an appropriate treatment and the patient is not eligible for
             a conventional myeloablative transplant because of organ dysfunction AND/OR

          -  Any patient, regardless of age, who has relapsed following prior autologous or
             allogeneic transplant for a hematologic malignancy AND/OR

          -  Any patient, regardless of age, with one of the following hematological malignancies:

               1. Multiple myeloma

                    1. refractory to or failure following conventional chemotherapy such as VAD
                       (Vincristine, Adriamycin and Dexamethasone), pulse decadron, or alkylating
                       agents, or

                    2. chromosomal abnormality associated with poor prognosis by cytogenetics or
                       FISH probe.

               2. Chronic lymphocytic leukemia patients, Rai stage 3 or 4 and relapsed
                  following/refractory to alkylating agents or nucleoside analog therapy

               3. Low grade lymphoma (small lymphocytic, follicular small cleaved cell, or
                  follicular mixed small cleaved and large cell) that is either relapsed or
                  refractory provided the disease is NOT rapidly progressive, NOT bulky, and no
                  mass exceeds 5 cm in greatest dimension.

        To be eligible a patient MUST meet all of the following criteria

          -  In addition to the above criteria ALL patients must meet the following minimum organ
             function:

               1. Cardiac: Ejection fraction at least 30%.

               2. Renal: Adequate renal function as defined by creatinine < 2.0mg OR creatinine
                  clearance >40 mg/min by 24-hour urine collection or GFR (Glomerular Filtration
                  Rate. (Gender and age-adjusted creatinine clearance >40ml/min by Gault-Cockroft
                  55 is acceptable for adults: (140 - age) x weight/72 x Scr [x 0.85 if female]).

               3. Pulmonary: FEV1 and FVC >60%.

               4. Hepatic: Total bilirubin <2.0 and AST (Aspartate Aminotransferase)/ALT (Alanine
                  Transaminase) < 3X institutional normal for age.

               5. Performance (adults): Karnofsky score must be at least 60; for pts. under 16,
                  Lansky score must be at least 60.

          -  Availability of a 5/6 or 6/6 HLA A, B, and DR identical relative who is willing and
             able to donate allogeneic stem cells. Serological, low resolution or mid resolution
             molecular typing will determine the degree of match for HLA (Human Leukocyte Antigen)
             class I regardless of high resolution DNA typing results. High resolution typing will
             be used to determine the degree of match for HLA-DR.

          -  No untreated or uncontrolled invasive infections. Patients still under therapy for
             presumed or proven infection are eligible provided there is clear evidence (radiologic
             and/or culture) that the infection is well controlled. Patients under treatment for
             infection will be enrolled only after clearance from the Principal Investigator.

          -  Not pregnant

        Patient Exclusion Criteria:

          -  acute leukemia

          -  HIV positive patients not eligible

          -  Any physical or psychological condition that, in the opinion of the investigator,
             would pose unacceptable risk to the patient

          -  Pregnant

        Donor Inclusion Criteria:

          -  5/6 or 6/6 HLA match for HLA-A, B, and DR

          -  Age 3-70 years, good general health

          -  No contraindication to G-CSF (Granulocyte Colony-Stimulating Factor)stimulation

          -  No contraindication to leukapheresis of peripheral blood stem cells

          -  Good general health

        Donor Exclusion Criteria:

          -  HIV positive or history of HIV risk factors

          -  Presence of other diseases transmissible by blood that pose unacceptable risk to the
             study subject.

          -  Pregnant

          -  Medical or psychological conditions that would make the donor unlikely to tolerate
             G-CSF - injections or leukapheresis