Donor Peripheral Stem Cell Transplant, Fludarabine, and Busulfan in Treating Patients With Hematologic Cancers
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
Intervention: busulfan; cyclosporine; fludarabine phosphate; mycophenolate mofetil; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Busulfan; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: recurrent adult acute myeloid leukemia; adult acute lymphoblastic leukemia in remission; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory anemia; refractory cytopenia with multilineage dysplasia; previously treated myelodysplastic syndromes; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia in remission; 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 phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; recurrent adult Hodgkin lymphoma; refractory multiple myeloma; recurrent adult acute lymphoblastic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; secondary acute myeloid leukemia; recurrent small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; recurrent adult lymphoblastic lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; recurrent adult Burkitt lymphoma; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes

Summary:

      Giving chemotherapy drugs, such as fludarabine and busulfan, before a donor peripheral stem
      cell transplant helps stop the growth of cancer cells. It also stops 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 cyclosporine and mycophenolate mofetil before and
      after the transplant may stop this from happening.

      PURPOSE: This phase II trial is studying the side effects of giving donor peripheral stem
      cell transplant together with fludarabine and busulfan and to see how well it works in
      treating patients with hematologic cancers.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosed with any of the following:

               -  Acute myeloid leukemia (AML), meeting 1 of the following criteria:

                    -  Recurrent disease in remission, defined as morphological remission with bone
                       marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study
                       treatment (cytogenetic or molecular remission is not required)

                    -  In first complete remission (CR1) with poor-risk cytogenetics, antecedent
                       hematological disease (i.e., myelodysplasia), or treatment-related leukemia

               -  Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

                    -  Recurrent disease in remission, defined as morphological remission with bone
                       marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study
                       treatment (cytogenetic or molecular remission is not required)

                    -  CR1 with Philadelphia chromosome or poor-risk cytogenetics

               -  Chronic myelogenous leukemia (CML), meeting the following criteria:

                    -  First or second chronic phase

                         -  Must be documented disease progression after imatinib mesylate therapy
                            OR documented lack of cytogenetic response 6 months post-imatinib
                            mesylate initiation OR imatinib mesylate intolerance

               -  Chronic lymphocytic leukemia (CLL), meeting the following criteria:

                    -  Recurrent disease after fludarabine-based therapy

                         -  Must have chemosensitive disease at the time of relapse, defined as
                            greater than 50% reduction of WBC and lymphadenopathy

               -  Recurrent Hodgkin lymphoma, recurrent non-Hodgkin lymphoma (NHL) (low-,
                  intermediate-, or high-grade disease*), or transformed NHL, meeting 1 of the
                  following criteria:

                    -  Received prior autologous transplantation and cytoreductive therapy at the
                       time of relapse to achieve complete remission (CR) or CR/unconfirmed (CRu)
                       as defined by the International Workshop

                    -  Relapsed disease that required more than 2 salvage regimens to achieve CR or
                       CRu

               -  Recurrent multiple myeloma, meeting the following criteria:

                    -  Must have received prior autologous transplantation and demonstrate
                       chemosensitivity at the time of relapse, defined as greater than 50%
                       reduction of M-component or plasma-cell marrow infiltration

               -  Myelodysplastic syndrome

                    -  Refractory anemia (RA)/RA with ringed sideroblasts (RARS), refractory
                       cytopenia with multilineage dysplasia (RCMD)/refractory cytopenia with
                       multilineage dysplasia with ringed sideroblasts (RCMD-RS), or RA with excess
                       blasts (RAEB) I, meeting the following criteria:

                         -  Must be transfusion-dependent and have an IPSS score ≥ 1.5, based on
                            WHO criteria

                         -  No RAEB II or del(5q)

          -  No uncontrolled CNS metastases

          -  5-6/6 HLA-matched sibling or 9-10/10 matched unrelated donor (both patient and donor)
             available

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status ≥ 50%

          -  Serum creatinine ≤ 2 mg/dL

          -  Not pregnant

          -  Fertile patients must use effective contraception

          -  50 years of age or older

               -  Patients 18-50 years of age are eligible if meeting 1 of the following criteria:

                    -  Have a preexisting medical condition

                    -  Received prior therapy (i.e., autologous transplantation) and are considered
                       to be too high risk for conventional myeloablative transplantation

          -  Must be willing to accept or comprehend irreversible sterility as a side effect of
             therapy

          -  No uncontrolled active infection

          -  No psychiatric illness or mental deficiency making compliance with treatment or
             informed consent impossible

          -  Cardiac ejection fraction ≥ 30%

          -  Corrected pulmonary-diffusing capacity ≥ 35%

          -  No serologic evidence of infection with HIV

          -  No decompensated liver disease with serum bilirubin > 2.0 mg/dL

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics