Ignite Creation Date:
2025-12-25 @ 4:18 AM
Ignite Modification Date:
2025-12-26 @ 3:19 AM
Study NCT ID:
NCT05959720
Status:
RECRUITING
Last Update Posted:
2025-05-07
First Post:
2023-07-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D054198', 'term': 'Precursor Cell Lymphoblastic Leukemia-Lymphoma'}, {'id': 'D018365', 'term': 'Neoplasm, Residual'}], 'ancestors': [{'id': 'D007945', 'term': 'Leukemia, Lymphoid'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D009385', 'term': 'Neoplastic Processes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D011241', 'term': 'Prednisone'}, {'id': 'D014750', 'term': 'Vincristine'}, {'id': 'D003630', 'term': 'Daunorubicin'}, {'id': 'C042705', 'term': 'pegaspargase'}, {'id': 'D003520', 'term': 'Cyclophosphamide'}, {'id': 'D003561', 'term': 'Cytarabine'}, {'id': 'D015122', 'term': 'Mercaptopurine'}, {'id': 'D008727', 'term': 'Methotrexate'}, {'id': 'D004317', 'term': 'Doxorubicin'}], 'ancestors': [{'id': 'D011244', 'term': 'Pregnadienediols'}, {'id': 'D011245', 'term': 'Pregnadienes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D014748', 'term': 'Vinca Alkaloids'}, {'id': 'D046948', 'term': 'Secologanin Tryptamine Alkaloids'}, {'id': 'D026121', 'term': 'Indole Alkaloids'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D054836', 'term': 'Indolizidines'}, {'id': 'D007212', 'term': 'Indolizines'}, {'id': 'D018943', 'term': 'Anthracyclines'}, {'id': 'D009279', 'term': 'Naphthacenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000617', 'term': 'Aminoglycosides'}, {'id': 'D006027', 'term': 'Glycosides'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D003562', 'term': 'Cytidine'}, {'id': 'D011741', 'term': 'Pyrimidine Nucleosides'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D001087', 'term': 'Arabinonucleosides'}, {'id': 'D009705', 'term': 'Nucleosides'}, {'id': 'D009706', 'term': 'Nucleic Acids, Nucleotides, and Nucleosides'}, {'id': 'D013438', 'term': 'Sulfhydryl Compounds'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D000630', 'term': 'Aminopterin'}, {'id': 'D011622', 'term': 'Pterins'}, {'id': 'D011621', 'term': 'Pteridines'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'All bone marrow or peripheral blood samples from diagnosis are going to be stored in a registered biobank. From bone marrow, DNA, RNA (Trizol) and mononuclear cryopreserved cells are going to be stored after Ficoll separated centrifugation. From peripheral blood, only DNA/RNA from buffy coat.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 180}, 'targetDuration': '2 Years', 'patientRegistry': True}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-09-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2030-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-05-03', 'studyFirstSubmitDate': '2023-07-17', 'studyFirstSubmitQcDate': '2023-07-17', 'lastUpdatePostDateStruct': {'date': '2025-05-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-07-25', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Overall survival (OS)', 'timeFrame': '4 years', 'description': 'cumulative proportion of patients alive (considering the time between the date of diagnosis and death or last follow-up)'}], 'secondaryOutcomes': [{'measure': 'Event-free survival (EFS)', 'timeFrame': '4 years', 'description': 'time between enrollment in the study and the occurrence of any event: refractoriness after the first two cycles of induction, death or relapse.'}, {'measure': 'Early death rate', 'timeFrame': '60 days', 'description': 'proportion of patients who died before the first bone marrow evaluation of response (after induction I)'}, {'measure': 'Complete response rate', 'timeFrame': '60 days', 'description': 'proportion of patients with bone marrow aspirate with less than 5% blasts and evidence of normal hematopoiesis; CSF without blasts and recovery of peripheral blood (neutrophils≥ 1,000/μL and platelets≥100,000/μL), without the need for transfusion'}, {'measure': 'Cumulative incidence of relapse', 'timeFrame': '4 years', 'description': 'rate of disease relapse after CR calculated considering death as a competing event.'}, {'measure': 'HSCT rate', 'timeFrame': '2 years', 'description': 'proportion of patients eligible for the protocol who were able to perform the procedure in their first CR'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Acute Lymphoid Leukemia', 'Minimal Residual Disease', 'Gene Abnormality', 'Chemotherapeutic Toxicity']}, 'referencesModule': {'references': [{'pmid': '35344469', 'type': 'BACKGROUND', 'citation': 'Silva WF, Amano MT, Perruso LL, Cordeiro MG, Kishimoto RK, de Medeiros Leal A, Nardinelli L, Bendit I, Velloso ED, Rego EM, Rocha V. Adult acute lymphoblastic leukemia in a resource-constrained setting: outcomes after expansion of genetic evaluation. Hematology. 2022 Dec;27(1):396-403. doi: 10.1080/16078454.2022.2052602.'}]}, 'descriptionModule': {'briefSummary': 'In this project, the investigators intend to start a prospective registry for patients with newly diagnosed Philadelphia-negative ALL from 16 years old and above in participating centers, provided that all patients will be treated with the same regimen (a pediatric regimen BFM-based incorporating peg-asparaginase). All diagnostic/follow-up (after induction and consolidation blocks) samples will be centrally biobanked at Instituto do Cancer do Estado de Sao Paulo. The main goal of this study is to examine whether the implementation of a pediatric protocol under a prospective registry can increase event-free survival (EFS) and overall survival (OS) of newly diagnosed patients in the participating centers.', 'detailedDescription': 'Notably, pediatric regimens for adult acute lymphoblastic leukemia (ALL) have resulted in better long-term outcomes, especially in the Philadelphia-negative counterpart. These regimens are essentially based on higher cumulative doses of asparaginase and the use of less myelotoxic agents, applying allogeneic transplantation only for high-risk ALL subsets. Recent metanalysis encompassing 27 clinical trials demonstrated an improved prognosis when these regimens are adopted. In adults, incorporation of these regimens has been hampered by a perception of higher toxicity and a more complex design, especially with asparaginase. Remarkably, this drug might bring side effects not usually seen with other cancer drugs, such as thrombosis, liver, and pancreatic toxicities. In addition, the incorporation of minimal residual disease (MRD) monitoring throughout the treatment protocol in a scheduled and standardized manner is considered paramount in the contemporary ALL treatment. Treating adult patients with acute leukemia under prospective studies allows accurate data collection and positively impacts the disease prognosis, creating a cooperative scientific environment. In Brazil, few data are available on the clinical- laboratory characteristics of ALL in adults and their outcomes under a standardized treatment protocol. Few single-center reports point to a worse overall survival rate when compared to developed countries. There is great heterogeneity across the centers regarding the treatment regimens and genetic/MRD assessment. In this project, the investigators intend to start a prospective registry for patients with newly diagnosed Philadelphia-negative ALL from 16 years old and above in participating centers, provided that all patients will be treated with the same regimen (a pediatric regimen BFM-based incorporating peg-asparaginase). All diagnostic/follow-up (after induction and consolidation blocks) samples will be centrally biobanked at Instituto do Cancer do Estado de Sao Paulo. At the diagnosis, a genetic characterization encompassing conventional karyotype, fluorescent in-situ hybridization (FISH), and molecular biology in our central laboratory will be performed to classify the cases. Genomic classification will include identifying Philadelphia- like B-cell ALL cases, a recent group of cases with worse prognosis, whose incidence seems higher in Hispanics. In Brazil, there is no study addressing this incidence and, more importantly, evaluating its impact on outcomes under a standardized treatment protocol. MRD analysis will also be centralized to standardize and validate our flow cytometry panel in a homogeneous cohort. Additionally, the investigators plan to assess baseline factors predictive of survival and relapse and those related to major toxicities such as infections, liver toxicity, and thrombosis.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '50 Years', 'minimumAge': '16 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'All patients from 16 years and above newly diagnosed with Philadelphia-negative ALL and after the signature of informed consent form (ICF). Patients between 16 and 17 years-old will sign a child assent along with a parental consent form. ICF application might be performed even under ALL suspicion only, given the need for sample collection before any therapy, ideally.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria: Patients between 16 and 50 years-old with newly diagnosed ALL, negative for Philadelphia chromosome not previously treated (except for hydroxyurea, corticosteroids, or intrathecal chemotherapy) with 20% or more lymphoblasts in bone marrow or peripheral blood.\n\nExclusion Criteria:\n\n* Burkitt leukemia\n* Prior myeloproliferative disease\n* Philadelphia chromosome positivity through whichever methodology (RT-PCR, FISH, or conventional karyotype)\n* ECOG\\>2 (appendix 3)\n* Total bilirubin\\>2x upper limit of normal (ULN)\n* Transaminases\\>5x ULN\n* Creatinine\\>2,5 mg/dl\n* Positive serology for HIV or HTLV\n* Heart failure NYHA Class III or IV (appendix 4)\n* Severe psychiatric disorder which prevents adequate compliance\n* Prior treatment with intravenous chemotherapy\n* Refusal to participate in the study\n* Down syndrome'}, 'identificationModule': {'nctId': 'NCT05959720', 'acronym': 'BRALLA', 'briefTitle': 'Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil', 'organization': {'class': 'OTHER', 'fullName': 'Instituto do Cancer do Estado de São Paulo'}, 'officialTitle': 'Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil - a Prospective Collaborative Study', 'orgStudyIdInfo': {'id': '3011/22'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Eligible patients', 'description': 'All patients deemed eligible to intensive protocol of treatment are going to be included as sole group. There is no intervention or control group in this trial.', 'interventionNames': ['Drug: Prednisone', 'Drug: Vincristin', 'Drug: Daunorubicin', 'Drug: Peg-asparaginase', 'Drug: Intrathecal Suspension', 'Drug: Cyclophosphamide', 'Drug: Cytarabine', 'Drug: Mercaptopurine', 'Drug: Methotrexate', 'Drug: Doxorubicin']}], 'interventions': [{'name': 'Prednisone', 'type': 'DRUG', 'description': '60 mg/m2 D1 to D21', 'armGroupLabels': ['Eligible patients']}, {'name': 'Vincristin', 'type': 'DRUG', 'description': '1.5 mg/m2 D1, D8, D15 and D22', 'armGroupLabels': ['Eligible patients']}, {'name': 'Daunorubicin', 'type': 'DRUG', 'description': '40 mg/m2 D1, D8, D15 and D22', 'armGroupLabels': ['Eligible patients']}, {'name': 'Peg-asparaginase', 'type': 'DRUG', 'description': '2000 UI/m2 D12 and D26', 'armGroupLabels': ['Eligible patients']}, {'name': 'Intrathecal Suspension', 'type': 'DRUG', 'description': 'MTX 12 mg, Dexamethasone 2 mg, Cytarabine 60 mg D1, D8, D15, D22, D29', 'armGroupLabels': ['Eligible patients']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'description': '1000 mg/m2 D36 and D64', 'armGroupLabels': ['Eligible patients']}, {'name': 'Cytarabine', 'type': 'DRUG', 'description': '75 mg/m2 D36 to D39, D43 to D46, D50 to D53 and D57 to D60', 'armGroupLabels': ['Eligible patients']}, {'name': 'Mercaptopurine', 'type': 'DRUG', 'description': '30 mg/m2 D36 to D63 and D1 to D56 of consolidation', 'armGroupLabels': ['Eligible patients']}, {'name': 'Methotrexate', 'type': 'DRUG', 'description': '3.000 mg/m2 D8, D22, D36 and D50', 'armGroupLabels': ['Eligible patients']}, {'name': 'Doxorubicin', 'type': 'DRUG', 'description': '30 mg/m2 D1 and D22', 'armGroupLabels': ['Eligible patients']}]}, 'contactsLocationsModule': {'locations': [{'zip': '01246000', 'city': 'São Paulo', 'state': 'São Paulo', 'status': 'RECRUITING', 'country': 'Brazil', 'contacts': [{'name': 'Wellington F Silva, MD PhD', 'role': 'CONTACT', 'email': 'wellington.fernandes@hc.fm.usp.br', 'phone': '551138944677'}], 'facility': 'Instituto do Cancer do Estado de Sao Paulo', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}], 'centralContacts': [{'name': 'Graziela Silva', 'role': 'CONTACT', 'email': 'graziela.sasilva@hc.fm.usp.br', 'phone': '551138934677'}, {'name': 'Bruna Moraes, MSc', 'role': 'CONTACT', 'email': 'pesquisa.hematologia@hc.fm.usp.br', 'phone': '551126628112'}], 'overallOfficials': [{'name': 'Wellington F Silva, MD PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Instituto do Cancer do Estado de São Paulo'}, {'name': 'Eduardo M Rego, MD PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Instituto do Cancer do Estado de São Paulo'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Instituto do Cancer do Estado de São Paulo', 'class': 'OTHER'}, 'collaborators': [{'name': 'Servier', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Wellington Fernandes', 'investigatorAffiliation': 'Instituto do Cancer do Estado de São Paulo'}}}}