Donor Stem Cell Transplant or Donor White Blood Cell Infusions in Treating Patients With Hematologic Cancer
Condition: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unusual Cancers of Childhood
MeSH terms: Lymphoma; Leukemia; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: anti-thymocyte globulin; filgrastim; busulfan; carmustine; cyclophosphamide; cyclosporine; cytarabine; etoposide; fludarabine phosphate; melphalan; methotrexate; methylprednisolone; mycophenolate mofetil; tacrolimus; peripheral blood stem cell transplantation; umbilical cord blood transplantation; radiation therapy
Intervention description: Intravenous, 1.5 mg/kg of body weight daily for 7 to 14 days The first dose should be administered over a minimum of 6 hours and over at least 4 hours on subsequent doses through a high-flow vein.; Will be given IV at 5 µg/kg/day. The first injection will be administered on day +7, i.e. 7 days after the hematopoietic stem cells are infused.
Will be administered until the ANC is 1500 / µl for 2 days. Dose and schedule of G-CSF administration is left to each center's discretion.; Patients who take the drug PO, busulfan will be administered at 1 mg/kg/ dose given by mouth every 6 hours for 16 consecutive doses. Pediatric patients who receive busulfan IV continuous infusion will receive a dose of 3.0 mg/kg/IBW if under the age of 2.Pediatric patients over the age of 2 will receive busulfan at a dose of 0.8 mg/kg/dose.; 300mg/m2 IV dissolved in 500 cc NS infused over 2 hours into right atrial catheter on day -6.; For transplantation, the drug is diluted in 250 to 500 cc of NS or D5W and administered IV over 2 hours.; Initial doses will be administered IV at a starting dose of 1.5 mg/kg BID. The infusion will vary from 2-24hr depending on the incidence of side-effects.; 400 mg/m2 dissolved in 200cc D5W and infused over 30 minutes into right atrial catheter on days -5, -4, -3, -2.; Etoposide administration 200 mg /m2 dissolved in 1 liter NS and infused over 2 hours into right atrial catheter. Infusion to begin after cytarabine administration on days -5, -4, -3, -2.
Etoposide administration 50 mg/kg IV over 24 hours, divided into 3 doses. Dilute in normal saline at a concentration of 0.4 mg/ml (Observe for precipitation). Administered IV with continuous infusion over 24 hours. Diuretics may be given for fluid overload.; Fludarabine administered at 30 mg/m2 IVPB infused over 30 minutes into right atrial catheter on days -4, -3, -2.
Fludarabine administered at 40 mg/m2 IVPB infused over 30 into the right atrial catheter on days -5, -4, -3, and -2.; 140 mg /m2 in concentration of 0.45 mg/ml of NS infused over 30 minutes into right atrial catheter on day -1.; Administered on days +1, +3, and +7.; Methyl-prednisolone is administered IV as a rapid infusion.; Mycophenolate may be used as a substitute for Methotrexate; A drug used to decrease the risk of graft versus host disease (GvHD).; The stem cells will be given to you by intravenous injection (through your vein) using a catheter that was placed prior to beginning chemotherapy. The stem cell infusion takes 1-6 hours.; The patient will receive ATG to improve the changes of engraftment and decrease their risk of graft versus host disease. The patient may receive ATG 3 times during their transplant regimen on days -3 through days -1; Radiation will be given to you 2 times a day for 3 or 4 days.
Intervention MeSH terms: Cytarabine; Cyclosporine; Mycophenolic Acid; Methylprednisolone; Cyclophosphamide; Melphalan; Busulfan; Carmustine; Methotrexate; Fludarabine; Fludarabine phosphate; Etoposide; Tacrolimus; Cyclosporins; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 200.0
Sex: All
Maximum age: 60 Years
Healthy volunteers: No
Keywords: adult acute lymphoblastic leukemia in remission; L1 adult acute lymphoblastic leukemia; L2 adult acute lymphoblastic leukemia; L3 adult acute lymphoblastic leukemia; recurrent adult acute lymphoblastic leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; childhood acute lymphoblastic leukemia in remission; L1 childhood acute lymphoblastic leukemia; L2 childhood acute lymphoblastic leukemia; L3 childhood acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; recurrent adult Hodgkin lymphoma; recurrent/refractory childhood Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; stage IV childhood Hodgkin lymphoma; adult acute myeloid leukemia in remission; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); childhood acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; recurrent childhood acute myeloid leukemia; myelodysplastic/myeloproliferative neoplasm, unclassifiable; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; secondary acute myeloid leukemia; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; refractory anemia; chronic myelomonocytic leukemia; childhood chronic myelogenous leukemia; chronic eosinophilic leukemia; primary myelofibrosis; chronic neutrophilic leukemia; de novo myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL negative; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; juvenile myelomonocytic leukemia; nodal marginal zone B-cell 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; 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 childhood small noncleaved 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 chronic lymphocytic leukemia; refractory hairy cell leukemia; refractory multiple myeloma; splenic marginal zone lymphoma; stage I multiple myeloma; stage II multiple myeloma; stage III adult Burkitt lymphoma; stage III adult Hodgkin 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 III chronic lymphocytic leukemia; 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; stage III multiple myeloma; stage III small lymphocytic 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 chronic lymphocytic leukemia; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV small lymphocytic lymphoma; stage III childhood Hodgkin lymphoma; stage III childhood large cell lymphoma; stage III childhood lymphoblastic lymphoma; stage III childhood small noncleaved cell lymphoma; stage IV childhood large cell lymphoma; stage IV childhood lymphoblastic lymphoma; stage IV childhood small noncleaved cell lymphoma; unusual cancers of childhood; childhood myelodysplastic syndromes

Summary:

      RATIONALE: A peripheral stem cell transplant or an umbilical cord blood transplant from a
      donor may be able to replace blood-forming cells that were destroyed by chemotherapy or
      radiation therapy. Giving an infusion of the donor's white blood cells (donor lymphocyte
      infusion) after the transplant may help destroy any remaining cancer cells
      (graft-versus-tumor effect). Sometimes the transplanted cells can make an immune response
      against the body's normal cells. Methotrexate, cyclosporine, tacrolimus, or
      methylprednisolone may stop this from happening.

      PURPOSE: This clinical trial is studying how well a donor stem cell transplant or donor white
      blood cell infusions work in treating patients with hematologic cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of 1 of the following*:

               -  Acute lymphoblastic leukemia in any disease phase

                    -  Patients with any of the following high-risk features are encouraged to
                       enroll:

                         -  Philadelphia chromosome positive disease

                         -  L3 morphology, especially in the presence of t(8;14), t(8;22), or
                            t(2;8)

                         -  Patients not in remission at day 28 of first induction

                         -  High LDH (i.e., ≥ 300 IU/mL at presentation)

                         -  Pre-B-cell, mixed lineage, or Burkitt's markers

                         -  Relapsed in the marrow while receiving continuous chemotherapy

                         -  Within 6 months after stopping chemotherapy

                         -  Relapse in one organ or extramedullary relapses in more than one organ
                            while still receiving chemotherapy

               -  Hodgkin's or non-Hodgkin's lymphoma beyond first complete remission (CR) or in
                  first CR with features of high-risk disease, including, but not limited to:

                    -  Lymphoma not in CR after 3 courses of primary therapy

                    -  Patients with bulky disease at presentation, especially bulky mediastinal
                       disease

                    -  Patients with LDH ≥ 300 IU/mL at presentation

                    -  Patients with extranodal disease

                    -  Patients with first remission within less than 1 year

                    -  Stage IV disease at presentation, especially with marrow involvement

                    -  Patients with high-intermediate or high International Index Scores

               -  Acute myeloid leukemia (AML) meeting the following criteria:

                    -  Beyond first remission or high-risk disease in first CR

                    -  Required multiple courses of induction therapy to achieve a remission

                    -  Had residual leukemia on day 14-28 bone marrow examination after initial
                       induction

                    -  Patients with any cytogenetic abnormality except inv 16 or t(8;21)

               -  Chronic myelogenous leukemia in the chronic or early accelerated phase of the
                  disease

                    -  Patients with blast crisis that can be induced back into chronic phase may
                       be transplanted in second chronic phase

               -  Myelodysplastic syndromes (MDS) meeting the following requirements:

                    -  Transfusion-dependent refractory anemia (RA), RA with excess blasts (RAEB),
                       RAEB in transformation, or chronic myelomonocytic leukemia (CMML)

                    -  Patients with MDS that present with or evolve to AML must be re-induced back
                       to remission prior to initiating a search for an unrelated donor NOTE:
                       *Patients with other hematologic malignancies not listed above, including
                       diseases such as chronic lymphocytic leukemia (CLL), multiple myeloma, or
                       rare pediatric malignancies, or patients who are felt to be at high-risk for
                       relapse but who do not have features listed, may be allowed at the
                       discretion of the investigator.

          -  Must have failed prior stem cell transplantation

          -  Must have a suitable unrelated allogeneic hematopoietic stem cell donor

               -  A 5/6 match degree is acceptable for unrelated bone marrow donors

               -  A 4/6 match degree is acceptable for unrelated cord blood units

        PATIENT CHARACTERISTICS:

          -  SWOG performance status (PS) 0-2 OR

          -  Karnofsky PS 50-100% OR

          -  Lansky PS 50-100%

          -  Creatinine clearance ≥ 45 mL/min

          -  Creatinine ≤ 2.5 mg/dL

          -  Bilirubin ≤ 2 mg/dL (abnormally high liver function tests allowed if the only source
             for the elevation is due to lymphoma of the liver)

          -  AST or ALT ≤ 2 times normal (abnormally high liver function tests allowed if the only
             source for the elevation is due to lymphoma of the liver)

          -  No patients at high risk of veno-occlusive disease

          -  Not pregnant or nursing

          -  Negative serum pregnancy test

          -  Fertile patients must use an effective contraceptive method

          -  DLCO ≥ 50% of predicted

          -  FEV_1/FVC ≥ 65% of predicted

          -  No current congestive heart failure (CHF) and/or LVEF ≥ 45%

          -  No myocardial infarction within the past 6 months

          -  No unstable angina within the past 6 months

          -  HIV negative

          -  Life expectancy must not be limited by disease other than malignancy

          -  No allergy to any chemotherapeutic agent included in the regimen

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics