Ignite Creation Date:
2025-12-24 @ 10:36 PM
Ignite Modification Date:
2025-12-26 @ 5:10 PM
Study NCT ID:
NCT00824135
Status:
COMPLETED
Last Update Posted:
2017-01-02
First Post:
2009-01-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D019337', 'term': 'Hematologic Neoplasms'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077866', 'term': 'Clofarabine'}, {'id': 'D018380', 'term': 'Hematopoietic Stem Cell Transplantation'}, {'id': 'D016853', 'term': 'Muromonab-CD3'}, {'id': 'D013852', 'term': 'Thiotepa'}, {'id': 'D008558', 'term': 'Melphalan'}, {'id': 'D009173', 'term': 'Mycophenolic Acid'}, {'id': 'D000069283', 'term': 'Rituximab'}, {'id': 'D016179', 'term': 'Granulocyte Colony-Stimulating Factor'}], 'ancestors': [{'id': 'D000227', 'term': 'Adenine Nucleotides'}, {'id': 'D011685', 'term': 'Purine Nucleotides'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D001087', 'term': 'Arabinonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D009711', 'term': 'Nucleotides'}, {'id': 'D012265', 'term': 'Ribonucleotides'}, {'id': 'D033581', 'term': 'Stem Cell Transplantation'}, {'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'}, {'id': 'D058846', 'term': 'Antibodies, Monoclonal, Murine-Derived'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D007074', 'term': 'Immunoglobulin G'}, {'id': 'D007132', 'term': 'Immunoglobulin Isotypes'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D013721', 'term': 'Triethylenephosphoramide'}, {'id': 'D001388', 'term': 'Aziridines'}, {'id': 'D001389', 'term': 'Azirines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D010649', 'term': 'Phenylalanine'}, {'id': 'D024322', 'term': 'Amino Acids, Aromatic'}, {'id': 'D000598', 'term': 'Amino Acids, Cyclic'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D002208', 'term': 'Caproates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D005227', 'term': 'Fatty Acids'}, {'id': 'D008055', 'term': 'Lipids'}, {'id': 'D003115', 'term': 'Colony-Stimulating Factors'}, {'id': 'D006023', 'term': 'Glycoproteins'}, {'id': 'D006001', 'term': 'Glycoconjugates'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D016298', 'term': 'Hematopoietic Cell Growth Factors'}, {'id': 'D016207', 'term': 'Cytokines'}, {'id': 'D036341', 'term': 'Intercellular Signaling Peptides and Proteins'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D001685', 'term': 'Biological Factors'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 34}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-12', 'completionDateStruct': {'date': '2016-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-12-30', 'studyFirstSubmitDate': '2009-01-15', 'studyFirstSubmitQcDate': '2009-01-15', 'lastUpdatePostDateStruct': {'date': '2017-01-02', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2009-01-16', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'To determine the MTD and DLT of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical HSCT with an engineered graft depleted of CD3+ cells obtained by negative selection with OKT3 on the CliniMACS system.', 'timeFrame': '30 days'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Stem Cell Transplantation, Hematopoietic', 'Peripheral Blood Stem Cell Transplantation', 'Maximal Tolerated Dose', 'Clofarabine', 'Hematological Malignancies', 'Apheresis'], 'conditions': ['Hematologic Malignancies']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'http://www.stjude.org', 'label': "St. Jude Children's Research Hospital"}, {'url': 'http://www.stjude.org/protocols', 'label': 'Clinical Trials Open at St. Jude'}]}, 'descriptionModule': {'briefSummary': 'Patients with refractory hematologic malignancies including those who develop recurrent disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal prognosis. Historically, both regimen-related mortality and disease recurrence have been significant causes of treatment failure in this heavily pre-treated patient population. The investigators institution has utilized mismatched family member donors for these patients for several reasons: (1) Only 30% of patients have matched related donors available; (2) transplantation can be performed more rapidly since the time to unrelated donor trans-plantation averages 3 to 4 months; (3) the alloimmune reactivity of natural killer (NK) cells following haploidentical HSCT has been shown to reduce relapse rates in certain patient groups; and, (4) no other curative treatment options are available.\n\nIn the present trial, the investigators propose a novel conditioning regimen using clofarabine in an effort to enhance cytotoxicity while simultaneously reducing regimen related toxicity. In this phase I trial, the goal is to determine the maximum tolerated dose (MTD) of clofarabine when used in combination with melphalan and thiotepa pre-transplant.', 'detailedDescription': 'The primary objective of this trial is to determine the maximum tolerated dose of clofarabine in combination with thiotepa and melphalan as a conditioning regimen for a haploidentical stem cell transplant with an engineered graft depleted of CD3+ cells. Study participants will children and young adults with refractory hematologic malignancies.\n\nSecondary objectives include the following:\n\n* To describe the one-year overall survival (OS) and event-free survival (EFS) rates in these study participants.\n* To determine the time to hematopoietic recovery and donor cell engraftment following this study treatment.\n* To estimate the cumulative incidence of relapse in study participants.\n* To estimate the incidence of overall grade II-IV and grade III-IV acute GVHD and the rate of chronic GVHD.\n* To estimate the incidence and describe the causes of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post HSCT.\n* To explore the biologic significance of soluble interleukin-2 (IL-2) receptor, tumor necrosis factor (TNF), and lymphocyte reconstitution (qualitative and quantitative, V beta spectratyping, TREC'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age less than or equal to 21 years old; may be greater than 21 years old if a previously treated St. Jude patient and within 3 years of completion of most recent prior disease specific therapy.\n* One of the following refractory hematologic malignancies (chemoresistant relapse or primary induction failure) or diagnoses:\n* ALL\n* AML (\\>25% blasts in the bone marrow)\n* secondary AML/MDS\n* CML in accelerated phase or blast crisis\n* juvenile myelomonocytic leukemia (JMML)\n* myelodysplastic syndrome (MDS)\n* Hodgkin or non-Hodgkin lymphoma (NHL) with residual or recurrent disease following autologous HSCT, who are unable to undergo autologous HSCT due to chemo-resistant disease or inability to have an acceptable quantity of tumor-free stem cells collected (\\> 1 x 108 TNC/kg marrow or \\> 1 x 106 CD34+/kg PBS\n* patients with a hematologic malignancy who have undergone prior allogeneic HSCT or who have a co-morbid condition that in the medical opinion of medical faculty (Division of Bone Marrow Transplantation and Cellular Therapy) makes standard myeloablation prohibitive\n* Does not have any other active malignancy other than the one for which this transplant is indicated\n* Cardiac shortening fraction greater than or equal to 25%\n* For pediatric patients, creatinine clearance greater than or equal to 90 ml/min/1.73 m2 according to the Schwartz formula for estimated GFR (ml/min/1.73m2) = k\\*height (cm)/serum creatinine (mg/dL). k is a proportionality constant that varies with age and is a function of urinary creatinine clearance per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 for adolescent boys\n* For adolescent or adult patients, serum creatinine 1.0 mg/dL; if serum creatinine 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where predicted GFR (ml/min/1.73 m2) = 186 x (serum creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black)\n* Forced vital capacity (FVC) greater than or equal to 40% of predicted value or pulse oximetry greater than or equal to 92% on room air.\n* Karnofsky or Lansky (age-dependent) performance score of greater than or equal to 50 (See APPENDIX A)\n* Does not have active acute or active chronic GVHD defined as requiring medical therapy.\n* Does not have active acute bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP).\n* Has a suitable HLA partially matched family member donor available for stem cell donation\n* Bilirubin less than or equal to 1.5 times the upper limit of normal for age.\n* Alanine aminotransferase (ALT) less than or equal to 1.5 times the upper limit of normal for age.\n* Aspartate aminotransferase (AST) less than or equal to 1.5 times the upper limit of normal for age.\n* Not pregnant (confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment).\n* Not lactating\n\nInclusion criteria (stem cell donor):\n\n* Partially HLA-matched family member.\n* At least 18 years of age.\n* HIV negative\n* Not pregnant (confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment).\n* Not lactating'}, 'identificationModule': {'nctId': 'NCT00824135', 'briefTitle': 'Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies', 'organization': {'class': 'OTHER', 'fullName': "St. Jude Children's Research Hospital"}, 'officialTitle': 'Haploidentical Hematopoietic Stem Cell Transplantation Using A Novel Clofarabine Containing Conditioning Regimen For Patients With Refractory Hematologic Malignancies', 'orgStudyIdInfo': {'id': 'REFLEX'}, 'secondaryIdInfos': [{'id': 'NCI-2011-03677', 'type': 'REGISTRY', 'domain': 'NCI Clinical Trial Registration Program'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': '1', 'interventionNames': ['Drug: Clofarabine', 'Procedure: Stem Cell Transplantation, Hematopoietic', 'Other: OKT3', 'Drug: Thiotepa', 'Drug: Melphalan', 'Drug: Mycophenolate mofetil', 'Drug: Rituximab', 'Other: G-CSF']}], 'interventions': [{'name': 'Clofarabine', 'type': 'DRUG', 'description': 'One dose intravenously every 24 hrs for five days total.\n\nDose level 1 Clofarabine 40 mg/m2/day intravenous Dose level 2 Clofarabine 45 mg/m2/day intravenous Dose Level 3 Clofarabine 50 mg/m2/day intravenous', 'armGroupLabels': ['1']}, {'name': 'Stem Cell Transplantation, Hematopoietic', 'type': 'PROCEDURE', 'description': 'Haploidentical Hematopoietic Stem Cell Transplantation (two infusions, one on day 0 and the other on day +1)', 'armGroupLabels': ['1']}, {'name': 'OKT3', 'type': 'OTHER', 'otherNames': ['Orthoclone OKT3'], 'description': 'Start at 0.0125 mg/kg intravenous once a day, taper dose down incrementally and discontinue after 17 days total\n\nMuromonab-CD3', 'armGroupLabels': ['1']}, {'name': 'Thiotepa', 'type': 'DRUG', 'description': '5 mg/kg/day intravenous every 12 hours (2 doses total)', 'armGroupLabels': ['1']}, {'name': 'Melphalan', 'type': 'DRUG', 'description': '60mg/m2 intravenous every 12 hours for 2 doses total.', 'armGroupLabels': ['1']}, {'name': 'Mycophenolate mofetil', 'type': 'DRUG', 'otherNames': ['MMF', 'CellCept'], 'description': 'Mycophenolate mofetil 600 mg/m2 intravenous two times a day\n\n(continue for approximately 2 months or as clinically indicated)', 'armGroupLabels': ['1']}, {'name': 'Rituximab', 'type': 'DRUG', 'otherNames': ['Rituxin'], 'description': '375 mg/m2 intravenous for 1 dose total', 'armGroupLabels': ['1']}, {'name': 'G-CSF', 'type': 'OTHER', 'description': 'G-CSF 5 mcg/kg/day subcutaneous or intravenous until ANC greater than 2.000/mm3 for 2 consecutive days and then as clinically indicated.', 'armGroupLabels': ['1']}]}, 'contactsLocationsModule': {'locations': [{'zip': '38119', 'city': 'Memphis', 'state': 'Tennessee', 'country': 'United States', 'facility': "St. Jude Children's Research Hospital", 'geoPoint': {'lat': 35.14953, 'lon': -90.04898}}], 'overallOfficials': [{'name': 'Brandon Triplett, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "St. Jude Children's Research Hospital"}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "St. Jude Children's Research Hospital", 'class': 'OTHER'}, 'collaborators': [{'name': 'Genzyme, a Sanofi Company', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}