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, such as fludarabine, busulfan, and etoposide, before a donor
      umbilical cord blood stem cell transplant helps stop the growth of cancer 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 antithymocyte globulin before transplant and tacrolimus and prednisone after
      transplant may stop this from happening.

      PURPOSE: This phase I trial is studying how well donor umbilical cord blood transplant works
      in treating patients with advanced hematologic cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the safety and feasibility of performing donor umbilical cord blood
           transplantation (UCBT) in patients with advanced hematologic malignancies, in terms of >
           80% engraftment rate at day 100 post-transplant and ≤ 50% transplant-related mortality.

      Secondary

        -  Determine the toxicity of a myeloablative preparative regimen comprising busulfan,
           fludarabine, and etoposide prior to UCBT in these patients.

        -  Determine the neutrophil and platelet recovery in patients treated with this regimen.

        -  Determine the event-free and overall survival of patients treated with this regimen.

        -  Evaluate lineage-specific chimerism after UCBT and assess the contribution of each
           individual cord blood unit to post-transplantation hematopoiesis in these patients.

        -  Determine the incidence, severity, and timing of acute and chronic graft-vs-host disease
           in patients treated with this regimen.

      OUTLINE: This is a pilot study.

        -  Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3,
           busulfan IV over 2 hours 4 times daily on days -7 and -4, etoposide IV over 4 hours on
           day -3, and anti-thymocyte globulin IV over 6 hours on days -2 and -1.

        -  Donor umbilical cord blood transplantation (UCBT): Patients undergo donor UCBT on day 0.
           Beginning on day 7, patients receive sargramostim (GM-CSF) IV or subcutaneously once
           daily until blood counts recover.

        -  Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously over 24
           hours or orally twice daily beginning on day -2 and continuing until day 180 followed by
           a taper. Patients also receive oral prednisone twice daily on days 13-50 and then once
           daily on days 50-60, followed by a rapid taper.

      After completion of study treatment, patients are followed periodically for approximately 2
      years.

      PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
    

Intervention name(s): anti-thymocyte globulin; sargramostim; busulfan; etoposide; fludarabine phosphate; prednisone; tacrolimus; allogeneic hematopoietic stem cell transplantation; umbilical cord blood transplantation
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention MeSH terms: Prednisone; Fludarabine; Fludarabine phosphate; Etoposide; 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; recurrent adult acute myeloid leukemia; secondary acute myeloid leukemia; adult acute myeloid leukemia in remission; adult acute erythroid leukemia (M6); adult acute megakaryoblastic leukemia (M7); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); refractory multiple myeloma; adult acute lymphoblastic leukemia in remission; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; stage II multiple myeloma; stage III multiple myeloma; recurrent adult acute lymphoblastic leukemia; recurrent adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; recurrent mantle cell lymphoma; stage III mantle cell lymphoma; recurrent adult Hodgkin lymphoma; stage III adult Hodgkin lymphoma; 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); de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; recurrent adult T-cell leukemia/lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult T-cell leukemia/lymphoma; stage IV mantle cell lymphoma; stage III adult T-cell leukemia/lymphoma; stage I multiple myeloma