Low-Dose Fludarabine, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer
Condition: Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant helps stop both
      the growth of cancer cells and the patient's immune system from rejecting the donor's stem
      cells. When the healthy stem cells from a donor are infused into the patient, they may help
      the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
      Sometimes the transplanted cells from a donor can make an immune response against the body's
      normal cells. Giving chemotherapy, such as fludarabine and busulfan, and antithymocyte
      globulin before transplant and tacrolimus and mycophenolate mofetil after transplant may stop
      this from happening.

      PURPOSE: This clinical trial is studying how well giving low-dose fludarabine and busulfan
      together with anti-thymocyte globulin, followed by donor umbilical cord blood transplant
      works in treating patients with advanced hematologic cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Assess the feasibility of performing umbilical cord blood transplants in older patients
           or younger infirm patients with advanced hematologic malignancies using a
           reduced-intensity preparative regimen, as determined by > 80% engraftment rate at day
           180 and a < 50% transplant-related mortality rate at day 100.

      Secondary

        -  Describe the time to neutrophil and platelet recovery in patients treated with this
           regimen.

        -  Determine disease-specific, event-free, and overall survival rate at days 180 and 360.

        -  Determine the incidence, severity, and timing of acute and chronic graft-versus-host
           disease in patients treated with this regimen.

        -  Evaluate T-cell, B-cell, and natural killer cell recovery in patients treated with this
           regimen.

        -  Assess lineage-specific chimerism after transplantation and describe the contribution of
           each individual cord blood unit to post-transplantation hematopoiesis.

      OUTLINE: This is a pilot study.

        -  Reduced-intensity preparative regimen: Patients receive fludarabine IV over 30 minutes
           on days -8 to -4, busulfan IV over 2 hours 4 times daily on days -4 and -3, and
           anti-thymocyte globulin IV over 6 hours on days -3 to -1.

        -  Allogeneic umbilical cord blood transplantation: Patients undergo allogeneic umbilical
           cord blood transplant on day 0. Patients receive sargramostim (GM-CSF) subcutaneously or
           IV beginning on day 7 and continuing until blood counts recover.

        -  Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV
           continuously over 24 hours or orally (as tolerated) beginning on day -2 and continuing
           for approximately 9 months. Patients also receive oral mycophenolate mofetil twice daily
           on days 1-50.

      After completion of study treatment, patients are followed periodically for 2 years.

      PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
    

Intervention name(s): anti-thymocyte globulin; sargramostim; busulfan; fludarabine phosphate; mycophenolate mofetil; tacrolimus; umbilical cord blood transplantation
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Procedure
Intervention MeSH terms: Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Busulfan; Tacrolimus; Antilymphocyte Serum; Sargramostim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; angioimmunoblastic T-cell lymphoma; blastic phase chronic myelogenous leukemia; chronic myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; de novo myelodysplastic syndromes; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; anaplastic large cell lymphoma; nodal marginal zone B-cell lymphoma; previously treated myelodysplastic syndromes; recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; recurrent adult T-cell leukemia/lymphoma; recurrent adult Hodgkin lymphoma; recurrent adult diffuse large cell lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent mycosis fungoides/Sezary syndrome; recurrent small lymphocytic lymphoma; refractory chronic lymphocytic leukemia; stage III adult T-cell leukemia/lymphoma; refractory multiple myeloma; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; secondary myelodysplastic syndromes; splenic marginal zone lymphoma; stage I multiple myeloma; stage II multiple myeloma; stage IV adult T-cell leukemia/lymphoma; stage III adult Hodgkin lymphoma; stage III adult diffuse large cell lymphoma; stage III chronic lymphocytic leukemia; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage III multiple myeloma; stage III small lymphocytic lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult diffuse large cell lymphoma; stage IV chronic lymphocytic leukemia; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV small lymphocytic lymphoma