Ignite Creation Date:
2025-12-25 @ 2:43 AM
Ignite Modification Date:
2026-01-07 @ 1:47 PM
Study NCT ID:
NCT00013533
Status:
COMPLETED
Last Update Posted:
2019-12-16
First Post:
2001-03-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pilot Study of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006689', 'term': 'Hodgkin Disease'}, {'id': 'D007945', 'term': 'Leukemia, Lymphoid'}, {'id': 'D015456', 'term': 'Leukemia, Biphenotypic, Acute'}, {'id': 'D009190', 'term': 'Myelodysplastic Syndromes'}, {'id': 'D008228', 'term': 'Lymphoma, Non-Hodgkin'}, {'id': 'D008223', 'term': 'Lymphoma'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009369', 'term': 'Neoplasms'}], 'ancestors': [{'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D033581', 'term': 'Stem Cell Transplantation'}], 'ancestors': [{'id': 'D017690', 'term': 'Cell Transplantation'}, {'id': 'D064987', 'term': 'Cell- and Tissue-Based Therapy'}, {'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D014180', 'term': 'Transplantation'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 30}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2001-03-14'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-05-07', 'completionDateStruct': {'date': '2015-05-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-12-13', 'studyFirstSubmitDate': '2001-03-20', 'studyFirstSubmitQcDate': '2001-03-20', 'lastUpdatePostDateStruct': {'date': '2019-12-16', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2001-03-21', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2008-03-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'To determine the efficacy and safety of this chemotherapy regimen in facilitating donor engraftment after allogeneic bone marrow transplantation (BMT).'}, {'measure': 'Safety/Efficacy', 'timeFrame': '5 years'}], 'secondaryOutcomes': [{'measure': 'Toxicity of regimen', 'timeFrame': '5 years'}, {'measure': 'To determine the toxicity of this non-myelablative allogeneic BMT regimen.'}, {'measure': 'fludarabine-based induction reducing T-cells', 'timeFrame': '5 years'}, {'measure': 'immune suppression', 'timeFrame': '5 years'}, {'measure': 'IL-7 levels', 'timeFrame': '5 years'}, {'measure': 'cytokine profiles', 'timeFrame': '5 years'}, {'measure': 'response rates and DFS', 'timeFrame': '5 years'}, {'measure': 'incidence and severity of GVHD', 'timeFrame': '5 years'}, {'measure': 'response rates, DFS rates, and incidence and severity ofGVHD following withdrawal of immunosuppression and donorlymphocyte infusions (DLI) for patients who developprogressive disease after day +28 post-transplant', 'timeFrame': '5 years'}]}, 'conditionsModule': {'keywords': ['Leukemia', 'Myelodysplastic Syndrome', 'Bone Marrow Transplant', 'Pediatric Oncology', 'Lymphoma', 'Efficacy', 'Safety', 'Childhood Cancer'], 'conditions': ['Hodgkin Lymphoma', 'Lymphocytic Leukemia', 'Mixed Cell Leukemia', 'Myelodysplastic Syndrome', "Non Hodgkin's Lymphoma", 'CML', 'ALL', 'AML', 'Lymphoma']}, 'referencesModule': {'references': [{'pmid': '8338938', 'type': 'BACKGROUND', 'citation': 'Kantarjian HM, Deisseroth A, Kurzrock R, Estrov Z, Talpaz M. Chronic myelogenous leukemia: a concise update. Blood. 1993 Aug 1;82(3):691-703. No abstract available.'}, {'pmid': '9718381', 'type': 'BACKGROUND', 'citation': 'Pui CH, Evans WE. Acute lymphoblastic leukemia. N Engl J Med. 1998 Aug 27;339(9):605-15. doi: 10.1056/NEJM199808273390907. No abstract available.'}, {'pmid': '3523250', 'type': 'BACKGROUND', 'citation': 'Rivera GK, Buchanan G, Boyett JM, Camitta B, Ochs J, Kalwinsky D, Amylon M, Vietti TJ, Crist WM. Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse. A Pediatric Oncology Group Study. N Engl J Med. 1986 Jul 31;315(5):273-8. doi: 10.1056/NEJM198607313150501.'}]}, 'descriptionModule': {'briefSummary': 'Background:\n\n* Allogeneic blood and marrow stem cell transplantation (BMT) plays an important role in the curative treatment of a number of pediatric malignancies. Unfortunately, the success of conventional allogeneic BMT is limited in part by the multiple toxicities associated with myeloablative preparative regimens.\n* Non-myeloablative pre-transplant regimens are associated with less toxic side effects than standard BMT. Recently, a novel immunosuppressive, non-myeloablative pre-transplant chemotherapy regimen has been shown to facilitate complete donor engraftment in an adult trial at the NCI.\n\nObjectives:\n\nThe primary objective of this protocol is to evaluate the efficacy and safety of this treatment approach in pediatric patients with hematopoietic malignancies\n\nEligibility:\n\nInclusion Criteria\n\nAge: Patient must be greater than or equal to 5 years and less than 22 years of age.\n\nDiagnosis:\n\n* Hodgkin s and Non-Hodgkin s Lymphoma: Refractory disease or relapse after salvage regimen.\n* Acute Myelogenous Leukemia: History of bone marrow relapse in remission (CR) #2 or greater.\n* Acute Lymphocytic Leukemia: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).\n* Acute Hybrid Leukemia including mixed lineage, biphenotypic and undifferentiated: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).\n* Myelodysplastic Syndrome: RAEB or RAEB-t with less than 10% blasts in marrow and blood.\n* Chronic Myelogenous Leukemia: Chronic phase or accelerated phase with less than 10% blasts in marrow and blood.\n* Juvenile Myelomonocytic Leukemia: less than 10% blasts in marrow and blood.\n\nPrior Therapy: Chemotherapy to achieve above criteria allowed. Prior BMT allowed as long as at least day 100+ post-prior BMT, no evidence of GVHD, and no detectable residual donor chimerism.\n\nDonor: First degree related donors, who are HLA matched (single HLA-A or B locus mismatch allowed), weight greater than or equal to 15 kilograms, and who meet standard donation criteria will be considered. The same donor from a prior BMT is allowed.\n\nECOG Performance Status: 0, 1, or 2. and life expectancy: greater than 3 months.\n\nLiver Function: Serum direct bilirubin less than 2.0 mg/dL and serum ALT and AST values less than or equal to 2.5x upper limit of normal. (Values above these levels may be accepted if due to malignancy.)\n\nRenal Function: Age adjusted normal serum creatinine or Cr clearance greater than or equal to 60 mL/min/1.73 m(2).\n\nPulmonary Function: DLCO greater than or equal to 50%.\n\nCardiac Function: LVEF greater than or equal to 45% by MUGA or LVSF greater than or equal to 28% by ECHO\n\nExclusion Criteria\n\n* Active CNS malignancy: Tumor mass on CT or leptomeningeal disease. (Patients with a history of CNS involvement and no current evidence of CNS disease are allowed.)\n* HIV infection, active hepatitis B or C infection: HbSAg or HCV seropositive and elevated liver transaminases.\n* Fanconi Anemia.\n* Lactating or pregnant females.\n\nDesign:\n\nPilot Study\n\n* Initial evaluation: Patient and donor will be screened for eligibility. G-CSF primed bone marrow derived stem cells will be collected from the donor.\n* Induction/Consolidation chemotherapy: 1 to 3 cycles will be given every 22 days depending on disease response, CD4 count, and toxicities.\n* Lymphoma: fludarabine, etoposide, doxorubicin, vincristine, cyclophohamide, prednisone, and filgrastim (EPOCH-fludarabine).\n* Leukemia and MDS: Fludarabine, cytarabine, and filgrastim (FLAG).\n* Transplantation: Fludarabine and cyclophosphamide will be administered over 4 days followed by bone marrow transplant. Patients will remain hospitalized until bone marrow recovery. Patients will be monitored closely at the NIH for at least 100 days post-BMT.\n* Post-transplant CNS prophylaxis for ALL: Standard post-transplant CNS prophylaxis will be employed with intrathecal methotrexate to decrease the risk of CNS relapse for all patients with ALL.\n* Total number of recipient and donors to be accrued is 56.', 'detailedDescription': 'Background:\n\n* Allogeneic blood and marrow stem cell transplantation (BMT) plays an important role in the curative treatment of a number of pediatric malignancies. Unfortunately, the success of conventional allogeneic BMT is limited in part by the multiple toxicities associated with myeloablative preparative regimens.\n* Non-myeloablative pre-transplant regimens are associated with less toxic side effects than standard BMT. Recently, a novel immunosuppressive, non-myeloablative pre-transplant chemotherapy regimen has been shown to facilitate complete donor engraftment in an adult trial at the NCI.\n\nObjectives:\n\nThe primary objective of this protocol is to evaluate the efficacy and safety of this treatment approach in pediatric patients with hematopoietic malignancies\n\nEligibility:\n\nInclusion Criteria\n\nAge: Patient must be greater than or equal to 5 years and less than 22 years of age.\n\nDiagnosis:\n\n* Hodgkin s and Non-Hodgkin s Lymphoma: Refractory disease or relapse after salvage regimen.\n* Acute Myelogenous Leukemia: History of bone marrow relapse in remission (CR) #2 or greater.\n* Acute Lymphocytic Leukemia: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).\n* Acute Hybrid Leukemia including mixed lineage, biphenotypic and undifferentiated: History of bone marrow relapse in CR #2 or greater (CR#1 with Philadelphia chromosome positive or prior induction failure).\n* Myelodysplastic Syndrome: RAEB or RAEB-t with less than 10% blasts in marrow and blood.\n* Chronic Myelogenous Leukemia: Chronic phase or accelerated phase with less than 10% blasts in marrow and blood.\n* Juvenile Myelomonocytic Leukemia: less than 10% blasts in marrow and blood.\n\nPrior Therapy: Chemotherapy to achieve above criteria allowed. Prior BMT allowed as long as at least day 100+ post-prior BMT, no evidence of GVHD, and no detectable residual donor chimerism.\n\nDonor: First degree related donors, who are HLA matched (single HLA-A or B locus mismatch allowed), weight greater than or equal to 15 kilograms, and who meet standard donation criteria will be considered. The same donor from a prior BMT is allowed.\n\nECOG Performance Status: 0, 1, or 2. and life expectancy: greater than 3 months.\n\nLiver Function: Serum direct bilirubin less than 2.0 mg/dL and serum ALT and AST values less than or equal to 2.5x upper limit of normal. (Values above these levels may be accepted if due to malignancy.)\n\nRenal Function: Age adjusted normal serum creatinine or Cr clearance greater than or equal to 60 mL/min/1.73 m(2).\n\nPulmonary Function: DLCO greater than or equal to 50%.\n\nCardiac Function: LVEF greater than or equal to 45% by MUGA or LVSF greater than or equal to 28% by ECHO\n\nExclusion Criteria\n\n* Active CNS malignancy: Tumor mass on CT or leptomeningeal disease. (Patients with a history of CNS involvement and no current evidence of CNS disease are allowed.)\n* HIV infection, active hepatitis B or C infection: HbSAg or HCV seropositive and elevated liver transaminases.\n* Fanconi Anemia.\n* Lactating or pregnant females.\n\nDesign:\n\nPilot Study\n\n* Initial evaluation: Patient and donor will be screened for eligibility. G-CSF primed bone marrow derived stem cells will be collected from the donor.\n* Induction/Consolidation chemotherapy: 1 to 3 cycles will be given every 22 days depending on disease response, CD4 count, and toxicities.\n* Lymphoma: fludarabine, etoposide, doxorubicin, vincristine, cyclophohamide, prednisone, and filgrastim (EPOCH-fludarabine).\n* Leukemia and MDS: Fludarabine, cytarabine, and filgrastim (FLAG).\n* Transplantation: Fludarabine and cyclophosphamide will be administered over 4 days followed by bone marrow transplant. Patients will remain hospitalized until bone marrow recovery. Patients will be monitored closely at the NIH for at least 100 days post-BMT.\n* Post-transplant CNS prophylaxis for ALL: Standard post-transplant CNS prophylaxis will be employed with intrathecal methotrexate to decrease the risk of CNS relapse for all patients with ALL.\n* Total number of recipient and donors to be accrued is 56.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '20 Years', 'minimumAge': '4 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "* INCLUSION CRITERIA PATIENTS:\n\nPatients with the following diagnoses will be considered:\n\n* Hodgkin's and Non-Hodgkin's Lymphoma: Refractory (non-CR) to primary treatment regimen; Refractory (non-CR) to or relapse after salvage regimen.\n* Acute Myelogenous Leukemia (AML): History of bone marrow relapse it CR number 2 or greater.\n* Acute Lymphocytic Leukemia (ALL): History of bone marrow relapse in CR number 2 or greater; complete remission #1 with Philadelphia chromosome positive or prior induction failure (subsequent induction regimen required to achieve CR).\n* Acute hybrid leukemia including mixed lineage, biphenotypic, and undifferentiated (AUL): History of bone marrow relapse in CR number 2 or greater; Complete remission #1 with Philadelphia chromosome positive or prior induction failure (second induction regimen required to achieve (CR).\n* Myelodysplastic Syndrome (MDS) excluding refractory anemia (RA) and RA with ringed sideroblasts (RARS): blasts less than 10% in marrow and blood.\n* Chronic Myelogenous Leukemia (CML): Chronic Phase; Accelerated Phase with blasts less than 10% in marrow and blood.\n* Juvenile Myelomonocytic Leukemia (JMML, J-CML): Blasts less than 10% in marrow and blood.\n\nPatients must be greater than or equal to 4 years and less than 22 years of age.\n\nPrior chemotherapy: Chemotherapy to achieve above noted criteria allowed. Prior autologous BMT allowed. Prior allogeneic BMT allowed as long as at least day +100 post-prior BMT, and no evidence of ongoing active GVHD.\n\nAvailability of 5 or 6 antigen genotypic HLA-matched first-degree relative donor (single HLA-A or B locus mismatch allowed).\n\nPerformance status of 0,1, or 2.\n\nLife expectancy greater than 3 months.\n\nLiver function: serum direct bilirubin less than 2.0 mg/dL, and serum ALT and AST values less than or equal to 2.5 times the upper limit of normal. Values above these levels may be accepted, at the discretion of the PI, if such elevations are thought to be due to malignancy (excluding acute leukemia).\n\nRenal function: age-adjusted normal serum creatinine or a creatinine clearance greater than or equal to 60 mL/min/1.73 m(2).\n\nPulmonary function: DLCO corrected for hemoglobin and alveolar volume greater than or equal to 50% of predicted.\n\nLeft ventricular function: Ejection fraction greater than or equal to 45% by MUGA or shortening fraction greater than or equal to 28% by ECHO.\n\nAbility to give informed consent. For patients less than 18 years old their legal guardian must give informed consent. Pediatric patients will be included in age appropriate discussion in order to obtain verbal assent.\n\nDurable power of attorney form completed (patients greater than 18 years of age only).\n\nPatients must not have an active CNS malignancy as defined by: lymphoma (tumor mass on CT scan or leptomeningeal disease), Leukemia (CNS 2 or CNS 3 classification), or NB (History of CNS involvement with no current evidence of CNS malignancy is NOT an exclusion).\n\nPatients must not be HIV positive.\n\nPatients must not have active hepatitis B or C infection as defined by seropositive for hepatitis B (HbSAg) or hepatitis C and elevated liver transaminases.\n\nFemale patients must not be lactating or pregnant (due to risk to fetus or newborn).\n\nPatients must not have high risk of inability to comply with transplant protocol as determined by principal investigator, social work, and BMT team.\n\nPatients must not have Fanconi Anemia (FA): patients with MDS must have a negative FA test.\n\nINCLUSION CRITERIA DONOR:\n\nFirst degree relative with genotypic identity at 5 or 6 HLA loci (single HLA-A or B locus mismatch allowed).\n\nWeight of greater than or equal to 15 kilograms.\n\nAdequate venous access for peripheral apheresis, or consent to use a temporary central venous catheter for apheresis (on Cohort #2, for possible future cell collection if needed).\n\nAbility to give informed consent. For donors less than 18 years of age, he/she must be the oldest eligible donor, their legal guardian must give informed consent, the donor must give verbal assent, and he/she must be cleared by social work and a mental health specialist to participate.\n\nDonor selection criteria will be in accordance with NIH/CC Department of Transfusion Medicine standards.\n\nEXLCUSION CRITERIA PATIENT:\n\nActive CNS malignancy as defined by:\n\n* Lymphoma: tumor mass on CT scan or leptomeningeal disease\n* Leukemia: CNS 2 or CNS 3 classification\n* NB: History of CNS involvement with no current evidence of CNS malignancy is NOT an exclusion.\n\nHIV positive.\n\nActive hepatitis B or C infection as defined by seropositive for hepatitis B (HbsAg) or hepatitis C and elevated liver transaminases.\n\nLactating or pregnant females.\n\nHigh risk of inability to comply with transplant protocol as determined by principal investigator, social work, and BMT team.\n\nFanconi Anemia (FA): Patients with MDS must have a negative FA test.\n\nEXCLUSION CRITERIA DONOR:\n\nHistory of medical illness which in the estimation of the PI or DTM physician poses prohibitive risk to donation including, but not limited to stroke, hypertension that is not controlled by medication, or heart disease. Individuals with symptomatic angina or a history of coronary artery bypass grafting or angioplasty will not be eligible. History of congenital hematologic, immunologic, or metabolic disorder which in the estimation of the PI poses prohibitive risk to the recipient.\n\nAnemia (Hb less than gm/dl) or thrombocytopenia (less than 100,000/ul).\n\nLactating or pregnant females.\n\nHIV positive.\n\nSeropositive for hepatitis B (HbsAg) or hepatitis C.\n\nHigh risk of inability to comply with transplant protocol as determined by principal investigator, social work, and BMT team."}, 'identificationModule': {'nctId': 'NCT00013533', 'briefTitle': 'Pilot Study of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies', 'nctIdAliases': ['NCT00020592'], 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': 'Pilot Study of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies', 'orgStudyIdInfo': {'id': '010125'}, 'secondaryIdInfos': [{'id': '01-C-0125'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': '1', 'description': 'Transplant with Induction Therapy', 'interventionNames': ['Procedure: Stem cell transplantation']}], 'interventions': [{'name': 'Stem cell transplantation', 'type': 'PROCEDURE', 'description': '\\>3 x 106/kg CD34+ stem cells by IV infusion', 'armGroupLabels': ['1']}]}, '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': 'Terry J Fry, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'National Cancer Institute (NCI)'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}