Combination Chemotherapy, Bone Marrow Transplant, and Post Transplant Cyclophosphamide 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: Busulfan; Cyclophosphamide
Intervention description: Days -7 to -4: 4 mg/kg PO daily OR 3.2 mg/kg IV daily OR 160 mg/m^2 daily (for pediatric recipients); Days -3, -2, +3, +4: 50 mg/kg IV daily
Intervention MeSH terms: Cyclophosphamide; Busulfan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 142.0
Sex: All
Minimum age: 6 Months
Maximum age: 65 Years
Healthy volunteers: No
Keywords: adult acute myeloid leukemia in remission; refractory anemia with excess blasts; 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); childhood acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; adult acute lymphoblastic leukemia in remission; childhood acute lymphoblastic leukemia in remission; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; chronic eosinophilic leukemia; chronic idiopathic myelofibrosis; chronic neutrophilic leukemia; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; stage II multiple myeloma; stage III multiple myeloma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; 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; previously treated myelodysplastic syndromes; 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 immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent childhood large cell lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent/refractory childhood Hodgkin lymphoma; recurrent adult Hodgkin lymphoma; recurrent small lymphocytic lymphoma; recurrent marginal zone lymphoma; 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 immunoblastic large cell lymphoma; stage III adult lymphoblastic 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 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; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; chronic myelomonocytic leukemia; refractory chronic lymphocytic leukemia; refractory multiple myeloma; secondary myelodysplastic syndromes; stage IV adult lymphoblastic lymphoma; childhood myelodysplastic syndromes

Summary:

      RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of
      cancer and abnormal cells and helps stop 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 cyclophosphamide, mycophenolate mofetil, or
      tacrolimus after transplant may stop this from happening.

      PURPOSE: This clinical trial is studying how well giving combination chemotherapy together
      with tacrolimus and mycophenolate mofetil 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 myeloid leukemia (AML), meeting 1 of the following criteria:

                    -  AML beyond first complete remission (CR1)

                    -  Refractory AML

                    -  AML arising from myelodysplastic syndromes (MDS)

                    -  Secondary AML

               -  MDS

                    -  Refractory anemia with excess blasts with > 10% blasts in bone marrow

               -  Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

                    -  ALL in CR1 with 1 of the following high-risk features:

                         -  Philadelphia chromosome (Ph)-positive disease

                         -  Less than 1 year of age at diagnosis

                         -  Cytogenetic abnormalities involving chromosome 11q23

                    -  ALL beyond CR1

                    -  Refractory ALL

               -  Chronic myeloid leukemia beyond first chronic phase

               -  Chronic myelomonocytic leukemia

               -  Chronic lymphocytic leukemia

                    -  Stage III-IV disease

                    -  Does not meet criteria for other bone marrow transplantation (BMT) studies

               -  Myeloproliferative disorders

                    -  Ph-negative disease

               -  Hodgkin's or non-Hodgkin's lymphoma

                    -  Chemotherapy-resistant disease

               -  Paroxysmal nocturnal hemoglobinuria with life-threatening thrombosis

               -  Multiple myeloma

                    -  Stage II or III disease

          -  Very high-risk disease

               -  Having an unrelated donor is considered a high-risk condition

          -  Meets medical criteria for myeloablative BMT for the Sidney Kimmel Comprehensive
             Cancer Center

          -  Bone marrow donor available, meeting 1 of the following criteria:

               -  Genotypically HLA-identical sibling

               -  Phenotypically matched first-degree relative

               -  Unrelated donor molecularly matched at HLA-A, -B, -C, -DRB1, and -DQB1

        PATIENT CHARACTERISTICS:

        Age

          -  6 months to 65 years

        Performance status

          -  Not specified

        Life expectancy

          -  Not specified

        Hematopoietic

          -  See Disease Characteristics

        Hepatic

          -  Not specified

        Renal

          -  Not specified

        Other

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  Not specified

        Chemotherapy

          -  See Disease Characteristics

        Endocrine therapy

          -  No concurrent dexamethasone as an antiemetic during immunosuppression therapy

        Radiotherapy

          -  Not specified

        Surgery

          -  Not specified

        Other

          -  No concurrent immunosuppressants until ≥ 24 hours after the completion of
             cyclophosphamide (post-transplantation)