Nctid:
NCT00001873
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-11-13"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D007938", "term"=>"Leukemia"}, {"id"=>"D009101", "term"=>"Multiple Myeloma"}, {"id"=>"D011289", "term"=>"Preleukemia"}, {"id"=>"D007945", "term"=>"Leukemia, Lymphoid"}, {"id"=>"D015451", "term"=>"Leukemia, Lymphocytic, Chronic, B-Cell"}, {"id"=>"D019337", "term"=>"Hematologic Neoplasms"}, {"id"=>"D009190", "term"=>"Myelodysplastic Syndromes"}, {"id"=>"D006086", "term"=>"Graft vs Host Disease"}], "ancestors"=>[{"id"=>"D010335", "term"=>"Pathologic Processes"}, {"id"=>"D009370", "term"=>"Neoplasms by Histologic Type"}, {"id"=>"D009369", "term"=>"Neoplasms"}, {"id"=>"D006402", "term"=>"Hematologic Diseases"}, {"id"=>"D054219", "term"=>"Neoplasms, Plasma Cell"}, {"id"=>"D020141", "term"=>"Hemostatic Disorders"}, {"id"=>"D014652", "term"=>"Vascular Diseases"}, {"id"=>"D002318", "term"=>"Cardiovascular Diseases"}, {"id"=>"D010265", "term"=>"Paraproteinemias"}, {"id"=>"D001796", "term"=>"Blood Protein Disorders"}, {"id"=>"D006474", "term"=>"Hemorrhagic Disorders"}, {"id"=>"D008232", "term"=>"Lymphoproliferative Disorders"}, {"id"=>"D007160", "term"=>"Immunoproliferative Disorders"}, {"id"=>"D007154", "term"=>"Immune System Diseases"}, {"id"=>"D001855", "term"=>"Bone Marrow Diseases"}, {"id"=>"D011230", "term"=>"Precancerous Conditions"}, {"id"=>"D008206", "term"=>"Lymphatic Diseases"}, {"id"=>"D015448", "term"=>"Leukemia, B-Cell"}, {"id"=>"D002908", "term"=>"Chronic Disease"}, {"id"=>"D020969", "term"=>"Disease Attributes"}, {"id"=>"D009371", "term"=>"Neoplasms by Site"}], "browseLeaves"=>[{"id"=>"M16355", "name"=>"Syndrome", "relevance"=>"LOW"}, {"id"=>"M11220", "name"=>"Lymphoma", "relevance"=>"LOW"}, {"id"=>"M10945", "name"=>"Leukemia", "asFound"=>"Leukemia", "relevance"=>"HIGH"}, {"id"=>"M27585", "name"=>"Precursor Cell Lymphoblastic Leukemia-Lymphoma", "relevance"=>"LOW"}, {"id"=>"M21314", "name"=>"Hematologic Neoplasms", "asFound"=>"Hematologic Neoplasms", "relevance"=>"HIGH"}, {"id"=>"M10955", "name"=>"Leukemia, Myeloid", "relevance"=>"LOW"}, {"id"=>"M18123", "name"=>"Leukemia, Myelogenous, Chronic, BCR-ABL Positive", "relevance"=>"LOW"}, {"id"=>"M12058", "name"=>"Multiple Myeloma", "asFound"=>"Multiple Myeloma", "relevance"=>"HIGH"}, {"id"=>"M27588", "name"=>"Neoplasms, Plasma Cell", "relevance"=>"LOW"}, {"id"=>"M9189", "name"=>"Graft vs Host Disease", "asFound"=>"Graft vs Host Disease", "relevance"=>"HIGH"}, {"id"=>"M18127", "name"=>"Leukemia, Myeloid, Acute", "relevance"=>"LOW"}, {"id"=>"M14164", "name"=>"Preleukemia", "asFound"=>"Myelodysplastic Syndrome", "relevance"=>"HIGH"}, {"id"=>"M10951", "name"=>"Leukemia, Lymphoid", "asFound"=>"Lymphocytic Leukemia", "relevance"=>"HIGH"}, {"id"=>"M12145", "name"=>"Myelodysplastic Syndromes", "asFound"=>"Myelodysplastic Syndrome", "relevance"=>"HIGH"}, {"id"=>"M18116", "name"=>"Leukemia, Lymphocytic, Chronic, B-Cell", "asFound"=>"Chronic Lymphocytic Leukemia", "relevance"=>"HIGH"}, {"id"=>"M12315", "name"=>"Neoplasms by Histologic Type", "relevance"=>"LOW"}, {"id"=>"M9490", "name"=>"Hematologic Diseases", "relevance"=>"LOW"}, {"id"=>"M21977", "name"=>"Hemostatic Disorders", "relevance"=>"LOW"}, {"id"=>"M5059", "name"=>"Blood Coagulation Disorders", "relevance"=>"LOW"}, {"id"=>"M17400", "name"=>"Vascular Diseases", "relevance"=>"LOW"}, {"id"=>"M13178", "name"=>"Paraproteinemias", "relevance"=>"LOW"}, {"id"=>"M5077", "name"=>"Blood Protein Disorders", "relevance"=>"LOW"}, {"id"=>"M9560", "name"=>"Hemorrhagic Disorders", "relevance"=>"LOW"}, {"id"=>"M11225", "name"=>"Lymphoproliferative Disorders", "relevance"=>"LOW"}, {"id"=>"M10206", "name"=>"Immunoproliferative Disorders", "relevance"=>"LOW"}, {"id"=>"M10200", "name"=>"Immune System Diseases", "relevance"=>"LOW"}, {"id"=>"M5134", "name"=>"Bone Marrow Diseases", "relevance"=>"LOW"}, {"id"=>"M14111", "name"=>"Precancerous Conditions", "relevance"=>"LOW"}, {"id"=>"M11203", "name"=>"Lymphatic Diseases", "relevance"=>"LOW"}, {"id"=>"M18115", "name"=>"Leukemia, B-Cell", "relevance"=>"LOW"}, {"id"=>"M6147", "name"=>"Chronic Disease", "relevance"=>"LOW"}, {"id"=>"M22700", "name"=>"Disease Attributes", "relevance"=>"LOW"}, {"id"=>"T3995", "name"=>"Myeloid Leukemia", "relevance"=>"LOW"}, {"id"=>"T182", "name"=>"Acute Myeloid Leukemia", "relevance"=>"LOW"}, {"id"=>"T175", "name"=>"Acute Lymphoblastic Leukemia", "relevance"=>"LOW"}, {"id"=>"T3533", "name"=>"Lymphoblastic Lymphoma", "relevance"=>"LOW"}, {"id"=>"T1303", "name"=>"Chronic Graft Versus Host Disease", "relevance"=>"LOW"}, {"id"=>"T1309", "name"=>"Chronic Myeloid Leukemia", "relevance"=>"LOW"}, {"id"=>"T3543", "name"=>"Lymphosarcoma", "relevance"=>"LOW"}, {"id"=>"T3947", "name"=>"Multiple Myeloma", "asFound"=>"Multiple Myeloma", "relevance"=>"HIGH"}, {"id"=>"T2832", "name"=>"Homologous Wasting Disease", "asFound"=>"Graft vs Host Disease", "relevance"=>"HIGH"}, {"id"=>"T188", "name"=>"Acute Non Lymphoblastic Leukemia", "relevance"=>"LOW"}, {"id"=>"T3993", "name"=>"Myelodysplastic Syndromes", "asFound"=>"Myelodysplastic Syndrome", "relevance"=>"HIGH"}, {"id"=>"T170", "name"=>"Acute Graft Versus Host Disease", "relevance"=>"LOW"}, {"id"=>"T1308", "name"=>"Chronic Lymphocytic Leukemia", "asFound"=>"Chronic Lymphocytic Leukemia", "relevance"=>"HIGH"}], "browseBranches"=>[{"name"=>"Symptoms and General Pathology", "abbrev"=>"BC23"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Neoplasms", "abbrev"=>"BC04"}, {"name"=>"Blood and Lymph Conditions", "abbrev"=>"BC15"}, {"name"=>"Immune System Diseases", "abbrev"=>"BC20"}, {"name"=>"Heart and Blood Diseases", "abbrev"=>"BC14"}, {"name"=>"Rare Diseases", "abbrev"=>"Rare"}]}, "interventionBrowseModule"=>{"browseLeaves"=>[{"id"=>"M18961", "name"=>"Cyclosporine", "relevance"=>"LOW"}, {"id"=>"M6730", "name"=>"Cyclosporins", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"Anti-Infective Agents", "abbrev"=>"Infe"}, {"name"=>"Antirheumatic Agents", "abbrev"=>"ARhu"}, {"name"=>"Dermatologic Agents", "abbrev"=>"Derm"}, {"name"=>"All Drugs and Chemicals", "abbrev"=>"All"}]}}, "protocolSection"=>{"designModule"=>{"phases"=>["PHASE2"], "studyType"=>"INTERVENTIONAL", "designInfo"=>{"allocation"=>"NON_RANDOMIZED", "maskingInfo"=>{"masking"=>"NONE"}, "primaryPurpose"=>"TREATMENT", "interventionModel"=>"SINGLE_GROUP"}, "enrollmentInfo"=>{"type"=>"ACTUAL", "count"=>102}}, "statusModule"=>{"overallStatus"=>"COMPLETED", "startDateStruct"=>{"date"=>"1999-02-22"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2017-06-13", "completionDateStruct"=>{"date"=>"2017-06-13", "type"=>"ACTUAL"}, "lastUpdateSubmitDate"=>"2018-09-25", "studyFirstSubmitDate"=>"1999-11-03", "studyFirstSubmitQcDate"=>"1999-11-03", "lastUpdatePostDateStruct"=>{"date"=>"2018-09-26", "type"=>"ACTUAL"}, "studyFirstPostDateStruct"=>{"date"=>"1999-11-04", "type"=>"ESTIMATED"}, "primaryCompletionDateStruct"=>{"date"=>"2007-12-28", "type"=>"ACTUAL"}}, "outcomesModule"=>{"primaryOutcomes"=>[{"measure"=>"The proportion of patients with clinically significant acute GHVD (Grade II or higher) following the T depleted PBPC transplant (and before D45 add-back).", "timeFrame"=>"Day 45"}]}, "conditionsModule"=>{"keywords"=>["Peripheral Blood Stem Cells", "Cyclosporine", "Cyclosphosphamide", "Whole Body Irradiation", "Donor Apheresis", "Leukemic Relapse", "Graft vs. Host Disease", "Graft-Versus-Leukemia", "Graft-Versus-Myeloma", "Chronic Myelogenous Leukemia", "Acute Lymphoblastic Leukemia", "Acute Myelogenous Leukemia", "Myelodysplastic Syndromes", "Multiple Myeloma", "Chronic Lymphocytic Leukemia", "Non-Hodgkin's Lymphoma"], "conditions"=>["Chronic Lymphocytic Leukemia", "Graft vs Host Disease", "Hematologic Neoplasm", "Multiple Myeloma", "Myelodysplastic Syndrome"]}, "referencesModule"=>{"references"=>[{"pmid"=>"7534141", "type"=>"BACKGROUND", "citation"=>"Schmitz N, Dreger P, Suttorp M, Rohwedder EB, Haferlach T, Loffler H, Hunter A, Russell NH. Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor). Blood. 1995 Mar 15;85(6):1666-72."}, {"pmid"=>"7534140", "type"=>"BACKGROUND", "citation"=>"Bensinger WI, Weaver CH, Appelbaum FR, Rowley S, Demirer T, Sanders J, Storb R, Buckner CD. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood. 1995 Mar 15;85(6):1655-8."}, {"pmid"=>"8991536", "type"=>"BACKGROUND", "citation"=>"Veltri S, Smith JW 2nd. Interleukin 1 trials in cancer patients: a review of the toxicity, antitumor and hematopoietic effects. Stem Cells. 1996 Mar;14(2):164-76. doi: 10.1002/stem.140164."}, {"pmid"=>"23524640", "type"=>"DERIVED", "citation"=>"McIver ZA, Yin F, Hughes T, Battiwalla M, Ito S, Koklanaris E, Haggerty J, Hensel NF, Barrett AJ. Second hematopoietic SCT for leukemia relapsing after myeloablative T cell-depleted transplants does not prolong survival. Bone Marrow Transplant. 2013 Sep;48(9):1192-7. doi: 10.1038/bmt.2013.39. Epub 2013 Mar 25."}, {"pmid"=>"23065508", "type"=>"DERIVED", "citation"=>"McIver Z, Melenhorst JJ, Wu C, Grim A, Ito S, Cho I, Hensel N, Battiwalla M, Barrett AJ. Donor lymphocyte count and thymic activity predict lymphocyte recovery and outcomes after matched-sibling hematopoietic stem cell transplant. Haematologica. 2013 Mar;98(3):346-52. doi: 10.3324/haematol.2012.072991. Epub 2012 Oct 12."}]}, "descriptionModule"=>{"briefSummary"=>"Cancers of the blood, sometimes referred to as hematologic malignancies, are disorders of bone marrow cells that lead to the failure of the normal function of bone marrow and the uncontrolled growth of cancerous cells in the bone marrow. These cancerous cells can spill over into the bloodstream and affect other organs causing widespread symptoms. The disease is life threatening because it blocks the normal function of the marrow, which is to produce red cells (preventing anemia), white cells (preventing infection), and platelets (preventing progression).\n\nBone marrow transplants are a potential form of therapy for patients with hematologic malignancies. However, BMT is a complicated procedure and can be associated with dangerous side effects.\n\nIn this study researchers are attempting to find ways to reduce the complications of BMT, so that it would be possible to use it more safely and can be offered more patients. In order to do this, researchers are developing new techniques to make BMT safer. It requires making small changes to the standard procedure, which may improve the outcome.\n\nThe experimental procedures researchers are evaluating are:\n\n1. \\<TAB\\>T-cell depleted peripheral blood progenitor cell (PBPC) transplantation\n2. \\<TAB\\> Cyclosporine given immediately after the transplant\n3. \\<TAB\\>Add-back of donor lymphocytes\n\nPatients undergoing these experimental techniques must be monitored closely to see if any benefit or harmful effects will occur. Information gathered from this study can be used to develop further research studies and potential new therapies for hematologic malignancies.", "detailedDescription"=>"Bone marrow stem cell transplant studies carried out by the NHLBI BMT Unit have focused on approaches to optimize the stem cell and lymphocyte dose in order to improve transplant survival and increase the graft-vs.-leukemia effect. A CD34 stem cell dose of greater than 3 x 10(6)/kg was found to increase survival and reduce relapse, while a CD3+ lymphocyte dose of less than 1 x 10(5)/kg was associated with a very low incidence of GVHD. Although processing of 2 peripheral blood progenitor cell (PBPC) collections with the CellPro immunoabsorption method (combined CD34-positive selection and CD2-negative selection) provided an improvement over previous methods, the system did not always achieve these optimal cell doses. A recent preclinical evaluation by the Department of Transfusion Medicine of a new immunomagnetic cell selection system available from Nexell, Inc. has demonstrated improved recovery of CD34+ cells and increased depletion of T lymphocytes, compared to the CellPro method. Incorporation of the Nexell system (Isolex 300i) into this clinical protocol will allow us to more consistently achieve CD34+ cell doses above the threshold of 3 x 10(6)/kg and CD3+ lymphocyte dosing in the region of 0.5 x 10(5)/kg. This will make it possible to test (1) the potential benefit of optimized transplant cell doses, (2) elimination of post transplant immunosuppression to enhance immune recovery.\n\nIn this study, we will use the Nexell Isolex 300i system to obtain more data on the relationship between CD34+ stem cell dose and outcome. In recipients who receive a T cell dose less than 0.5 x 10(5) CD3+ cells/kg the effect of withdrawing cyclosporine on development of GVHD will be evaluated in a cohort study: 20 patients will receive low dose cyclosporine. If the incidence of grade II or worse GVHD is 10% or less, no post transplant immunosuppression will be given to the next cohort and the incidence and severity of acute GVHD again assessed. Stopping rules for unacceptable GVHD severity will be applied. Two match groups HLA 6/6 and 5/6 donor-recipient pairs will be separately studied using this approach.\n\nIn a second phase of the study we will continue to accumulate data on T lymphocyte add-back given on day 45 and day 100 after transplant. For this phase, cyclosporine will be reintroduced on day 44 and continued until day 120 to accelerate immune recovery.\n\nUp to 70 patients aged between 10 and 55 years will be studied in each subset (HLA 6/6 and 5/6 matched cohorts). The major endpoint of the study is acute GVHD after transplant. We will also measure engraftment, acute and chronic GVHD, leukemic relapse, transplant-related and all causes of mortality, cytomegalovirus reactivation and leukemia-free survival. Patients will be followed for a minimum of 5 years."}, "eligibilityModule"=>{"sex"=>"ALL", "stdAges"=>["CHILD", "ADULT"], "maximumAge"=>"55 years", "minimumAge"=>"10 years", "healthyVolunteers"=>false, "eligibilityCriteria"=>"* INCLUSION CRITERIA - Patient:\n\nAges 10-55 years.\n\nChronic myelogenous leukemia, any of these categories: chronic phase, accelerated phase or blast transformation.\n\nAcute lymphoblastic leukemia, any of these categories: Adults (greater than 18 years) in first remission with high-risk features (presenting leukocyte count greater than 100,000/cu mm, karyotypes t9; 22, t4, t11, biphenotypic leukemia) All second or subsequent remissions, primary induction failure, partially responding or untreated relapse.\n\nAcute myelogenous leukemia (AML): AML in first remission except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8;21). All AML in second or subsequent remission, primary induction failure and resistant relapse.\n\nMyelodysplastic syndromes, any of these categories: refractory anemia with transfusion dependence, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia.\n\nMyeloproliferative disorders (myelofibrosis, polycythemia vera, essential thrombocythemia) in transformation to acute leukemia.\n\nChronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000 / mcl) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.\n\nNo major organ dysfunction precluding transplantation.\n\nDLCO greater than or equal to 60% predicted.\n\nLeft ventricular ejection fraction: greater than or equal to 40% predicted.\n\nECOG performance status of 0 or 1.\n\nFor adults: Written informed consent given by adults. For minors: Written informed consent from one parent or guardian. Informed oral consent from minors: The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.\n\nWomen of childbearing age with a negative pregnancy test may participate.\n\nEXCLUSION CRITERIA - Recipient (any of the following):\n\nPatient pregnant.\n\nAge less than 10 and greater than 55 years.\n\nECOG performance status of 2 or more.\n\nSevere psychiatric illness in the patient or donor. Mental deficiency sufficiently severe as to make compliance with the treatment unlikely, and making informed consent impossible.\n\nMajor anticipated illness or organ failure incompatible with survival from transplant.\n\nDLCO less than 60% predicted.\n\nLeft ventricular ejection fraction: less than 40% predicted.\n\nSerum creatinine greater than 3mg/dl.\n\nSerum bilirubin greater than 4 mg/dl.\n\nTransaminases greater than 3x upper limit of normal.\n\nHIV positive (donor or recipient).\n\nHistory of other malignancies except basal cell or squamous carcinoma of the skin, positive PAP smear and subsequent negative follow up.\n\nIndividuals with diseases listed above as eligible for this protocol, but where debility or age makes the risk of intensive myeloablative therapy unacceptable. These patients will be considered for a non-myeloablative allogeneic transplantation protocol (97-H-0202, 99-H-0050).\n\nINCLUSION CRITERIA - Donor:\n\nHLA 6/6 identical or 5/6 (one antigen mismatched) family donor.\n\nFit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke).\n\nFor adults: Written informed consent given by adults. For minors: Written informed consent from one parent or guardian. Informed oral consent from minors: The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.\n\nEXCLUSION CRITERIA - Donor (any of the following):\n\nPregnant or lactating.\n\nSevere psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.\n\nHIV positive."}, "identificationModule"=>{"nctId"=>"NCT00001873", "briefTitle"=>"The Role of Cyclosporine in Blood Cell Transplants With T-Cell Add-Back for Blood Cancers", "organization"=>{"class"=>"NIH", "fullName"=>"National Institutes of Health Clinical Center (CC)"}, "officialTitle"=>"Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T-Cell Add-Back for Hematological Malignancies - Role of Cyclosporine", "orgStudyIdInfo"=>{"id"=>"990046"}, "secondaryIdInfos"=>[{"id"=>"99-H-0046"}]}, "armsInterventionsModule"=>{"interventions"=>[{"name"=>"Isolex 300i plus MoAbs", "type"=>"DEVICE"}]}, "contactsLocationsModule"=>{"locations"=>[{"zip"=>"20892", "city"=>"Bethesda", "state"=>"Maryland", "country"=>"United States", "facility"=>"National Institutes of Health Clinical Center, 9000 Rockville Pike", "geoPoint"=>{"lat"=>38.98067, "lon"=>-77.10026}}], "overallOfficials"=>[{"name"=>"A. John Barrett, M.D.", "role"=>"PRINCIPAL_INVESTIGATOR", "affiliation"=>"National Heart, Lung, and Blood Institute (NHLBI)"}]}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"National Heart, Lung, and Blood Institute (NHLBI)", "class"=>"NIH"}}}}