Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer
Condition: Chronic 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: cyclophosphamide; fludarabine phosphate; mycophenolate mofetil; tacrolimus; allogeneic bone marrow transplantation; radiation therapy
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 210.0
Sex: All
Minimum age: 6 Months
Maximum age: 74 Years
Healthy volunteers: No
Keywords: adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; childhood acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; childhood chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; 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); chronic idiopathic myelofibrosis; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II mantle cell lymphoma; noncontiguous stage II marginal zone lymphoma; noncontiguous stage II small lymphocytic lymphoma; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult Hodgkin lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent/refractory childhood Hodgkin lymphoma; recurrent childhood large cell lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent childhood small noncleaved cell lymphoma; nodal marginal zone B-cell 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 small lymphocytic lymphoma; refractory multiple myeloma; relapsing chronic myelogenous leukemia; secondary myelodysplastic syndromes; splenic marginal zone lymphoma; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; stage III adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult Hodgkin lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; 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; polycythemia vera; essential thrombocythemia; stage III small lymphocytic lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV small lymphocytic lymphoma; stage IV adult Hodgkin lymphoma; childhood myelodysplastic syndromes

Summary:

      RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and
      radiation therapy before a donor bone marrow transplant helps stop the growth of cancer
      cells. Giving chemotherapy or radiation therapy before or after transplant also stops the
      patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem
      cells may replace the patient's immune system 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 fludarabine and cyclophosphamide
      together with total-body irradiation works in treating patients who are undergoing a donor
      bone marrow transplant for hematologic cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of 1 of the following hematologic malignancies:

               -  Acute leukemia

                    -  In second or subsequent complete remission (CR), as defined by absence of
                       abnormal blast population by flow cytometry

                    -  In first CR with any of the following poor-risk cytogenetic features:

                         -  Alteration of chromosome 5 or 7

                         -  Multiple abnormalities

                         -  Philadelphia chromosome positive

               -  Chronic phase chronic myelogenous leukemia (CML)

                    -  In first chronic phase and refractory to interferon alfa or imatinib
                       mesylate

                    -  In second or subsequent chronic phase

               -  Chronic lymphocytic leukemia, meeting 1 of the following criteria:

                    -  Received prior chemotherapy with a nucleoside analog and had remission
                       lasting < 6 months

                    -  Received 1 prior therapy and has any of the following high-risk features:

                         -  Cytogenetic abnormalities of 17p, 11q

                         -  Mutations of the Zap70 gene

                         -  Somatically unmutated immunoglobulin heavy chain variable region genes

               -  Hodgkin's lymphoma

                    -  Ineligible for autologous stem cell transplantation (SCT) due to any of the
                       following exclusion factors:

                         -  LVEF < 45%

                         -  FEV_1 or FVC < 50% of predicted (75% of predicted in patients with
                            prior thoracic or mantle radiotherapy)

                         -  Total bilirubin > 2.0 mg/dL (unless documented Gilbert's disease)

                         -  Creatinine > 2.0 mg/dL

               -  Non-Hodgkin's lymphoma (NHL)

                    -  Low-grade NHL allowed provided patient had a remission duration of < 1 year
                       after administration of any established, multi-agent chemotherapy regimen
                       (e.g., CVP, CHOP, or rituximab in combination with CHOP)

                    -  Intermediate- or high-grade NHL allowed provided patient is ineligible for
                       autologous SCT according to the criteria listed above

               -  Multiple myeloma

               -  Myelodysplastic syndromes

               -  Paroxysmal nocturnal hemoglobinuria

               -  Chronic myeloproliferative disorders other than CML, including any of the
                  following:

                    -  Chronic myelomonocytic leukemia

                    -  Agnogenic myeloid metaplasia (or myeloid metaplasia with myelofibrosis),
                       with hemoglobin < 10 g/dL OR WBC < 4,000/mm^3 or > 30,000/mm^3

                    -  Polycythemia vera or essential thrombocythemia in "spent" phase, with a
                       history of 2 of the following:

                         -  Marrow fibrosis

                         -  Splenomegaly

                         -  Cytopenia (i.e., absolute neutrophil count < 1,500/mm^3, platelet count
                            < 100,000/mm^3, hemoglobin < 10 g/dL)

                    -  Polycythemia vera or essential thrombocythemia with transformation to
                       myelodysplastic syndromes or acute myeloid leukemia (requires treatment to
                       achieve < 20% blasts in marrow)

          -  No smoldering myeloma

          -  Patients with acute myeloid leukemia or myelodysplastic syndromes must have had
             comprehensive cytogenetic evaluation of bone marrow specimen during active disease

          -  Ineligible for or refused bone marrow transplantation from an HLA-matched sibling or
             unrelated donor

          -  Ineligible for or refused autologous SCT

          -  Must have an HLA mismatched (i.e., 3/6, 4/6, or 5/6) related (first-degree relative)*
             donor available

               -  Donor ≥ 18 years of age NOTE: *Patients with an inherited recombinant HLA
                  haplotype may receive marrow from the parent in whose gamete the recombination
                  occurred

        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:

        Age

          -  6 months to 74 years

        Performance status

          -  ECOG 0-1

        Life expectancy

          -  Not specified

        Hematopoietic

          -  See Disease Characteristics

        Hepatic

          -  See Disease Characteristics

          -  Bilirubin < 3.1 mg/dL

        Renal

          -  See Disease Characteristics

        Cardiovascular

          -  See Disease Characteristics

          -  LVEF ≥ 35%

        Pulmonary

          -  See Disease Characteristics

          -  FEV_1 or FVC ≥ 40% of predicted in patients without prior thoracic or mantle
             radiotherapy (60% of predicted in patients with prior thoracic or mantle radiotherapy)

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  HIV negative

          -  Geographically accessible

          -  No debilitating medical or psychiatric illness that would preclude giving informed
             consent or receiving optimal treatment or follow-up

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  See Disease Characteristics

          -  No prior transfusions from donor

        Chemotherapy

          -  See Disease Characteristics

        Endocrine therapy

          -  Not specified

        Radiotherapy

          -  See Disease Characteristics

        Surgery

          -  Not specified