Umbilical Cord Blood (UCB) Transplant, Fludarabine, Melphalan, and Anti-thymocyte Globulin (ATG) in Treating Patients With Hematologic Cancer
Condition: Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Syndrome
Intervention: anti-thymocyte globulin; fludarabine phosphate; Melphalan; mycophenolate mofetil; tacrolimus; umbilical cord blood transplantation
Intervention description: anti-thymocyte globulin; fludarabine phosphate; melphalan; mycophenolate mofetil; tacrolimus; umbilical cord blood transplantation
Intervention MeSH terms: Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Melphalan; Tacrolimus; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: accelerated phase cml; adult ALL in remission; adult AML in remission; adult AML with 11q23 (MLL) abnormalities; adult AML 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); blastic phase chronic myelogenous leukemia; chronic myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; prolymphocytic leukemia; recurrent adult T-cell leukemia/lymphoma; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; refractory chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; recurrent adult Hodgkin lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; cutaneous B-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent mycosis fungoides/Sezary syndrome; adult grade III lymphomatoid granulomatosis; adult nasal type extranodal NK/T-cell lymphoma; Waldenstrom macroglobulinemia; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult grade III lymphomatoid granulomatosis; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; chronic idiopathic myelofibrosis; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes

Summary:

      RATIONALE: Giving low doses of chemotherapy before a donor umbilical cord blood transplant
      helps stop the growth of cancer cells. It may also stop the patient's immune system from
      rejecting the donor's stem cells. The donated stem cells may replace the patient's immune
      cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the
      transplanted cells from a donor can also make an immune response against the body's normal
      cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from
      happening.

      PURPOSE: This phase II trial is studying how well giving umbilical cord blood transplant
      together with fludarabine, melphalan, and antithymocyte globulin works in treating patients
      with hematologic cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of hematologic malignancy for which a reduced-intensity allogeneic stem cell
             transplantation is deemed clinically appropriate, including any of the following:

               -  Chronic myelogenous leukemia, meeting one of the following criteria:

                    -  In first chronic phase AND failed imatinib mesylate therapy, defined as
                       failure to obtain a hematologic remission by 3 months or major cytogenetic
                       response (Ph+ cells < 35%) by 12 months, or demonstrated clonal evolution or
                       disease progression while on therapy

                    -  In accelerated phase with < 15% blasts

                    -  In blast crisis that has entered into a second chronic phase following
                       induction chemotherapy

               -  Acute myelogenous leukemia, meeting one of the following criteria:

                    -  In second or subsequent completion remission*

                    -  Failed primary induction chemotherapy, but subsequently entered into a
                       complete remission* with ≤ 2 subsequent re-induction chemotherapy
                       treatment(s)

                    -  In first complete remission* with poor-risk cytogenetics NOTE: *Complete
                       remission is defined as < 5% blasts in bone marrow, no definitive evidence
                       of disease by morphology, flow cytometry, or genetic studies, and no
                       circulating blasts. Neutrophil and platelet count recovery will not be
                       required.

               -  Acute lymphoblastic leukemia, meeting one of the following criteria:

                    -  In second or subsequent complete remission

                    -  In first complete remission AND t(9;22)

               -  Myelodysplastic syndromes, meeting the following criteria:

                    -  High-risk disease, defined as International Prognostic Scoring System score
                       of ≥ 1.5

                    -  Less than 10% blasts at the time of study enrollment

               -  Chronic myelomonocytic leukemia

                    -  Less than 10% blasts at the time of study enrollment

               -  Myeloid metaplasia with myelofibrosis with poor-risk features, meeting one of the
                  following criteria:

                    -  Age < 55 years AND a Lille score of 1

                    -  Lille score of 2

                    -  Hemoglobin < 10 g/dL AND abnormal karyotype

               -  Chronic lymphocytic leukemia/prolymphocytic leukemia, meeting all of the
                  following criteria:

                    -  Rai stage I-IV disease

                    -  Failed ≥ 1 prior chemotherapy regimen, including fludarabine, or autologous
                       stem cell transplantation

                    -  Chemosensitive or stable, non-bulky disease prior to transplant

                    -  Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and
                       involved-field radiotherapy are not considered prior regimens)

               -  Low-grade B-cell non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma,
                  follicular center [grade 1 or 2] lymphoma, or marginal zone lymphoma), meeting
                  all of the following criteria:

                    -  Failed ≥ 1 prior chemotherapy regimen or autologous stem cell
                       transplantation

                    -  Chemosensitive or stable, non-bulky disease prior to transplant

                    -  Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and
                       involved-field radiotherapy are not considered prior regimens)

               -  Intermediate-grade B-cell or T-cell NHL or mantle cell NHL, meeting all of the
                  following criteria:

                    -  Failed to achieve remission or recurred after either conventional
                       chemotherapy or autologous stem cell transplantation

                    -  Chemosensitive, non-bulky disease prior to transplant

               -  Hodgkin lymphoma, meeting all of the following criteria:

                    -  Relapsed after prior autologous stem cell transplantation or after ≥ 2
                       combination chemotherapy regimens AND ineligible for autologous peripheral
                       blood stem cell transplantation

                    -  Chemosensitive, non-bulky disease prior to transplant

               -  Multiple myeloma, meeting one of the following criteria:

                    -  Relapsed after autologous stem cell transplantation

                    -  Relapsed after conventional therapies AND not a candidate for autologous
                       stem cell transplantation

          -  No HLA-matched related or unrelated donor available

          -  Has two umbilical cord blood units available that are matched at ≥ 4/6 HLA A, B, and
             DRB1 with the patient and with each other (HLA C and DQ will not be used in the match
             strategy)

               -  Total combined nucleated cell dose from the 2 umbilical cord blood units must be
                  > 3.7 x 10^7 nucleated cells/kg (pre-freeze dose) NOTE: A new classification
                  scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology
                  of "indolent" or "aggressive" lymphoma will replace the former terminology of
                  "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the
                  former terminology.

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status 80-100%

          -  Adapted, weighted Charlson Comorbidity Index < 3

          -  Serum creatinine ≤ 2.0 mg/dL

          -  AST or ALT < 3 times upper limit of normal (ULN)

          -  Bilirubin < 1.5 times ULN

          -  Not pregnant or nursing

          -  LVEF ≥ 40%

          -  DLCO > 50%

          -  No hypoxia at rest with oxygen saturation < 92% on room air (corrected with
             bronchodilator therapy)

          -  No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral
             infection)

          -  No active hepatitis B or C infection that, in the opinion of a gastroenterologist or
             the transplant committee, places the patient at moderate- to high-risk for developing
             severe hepatic disease

          -  No HIV infection

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics