Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

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Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Congenital Abnormalities

Neoplasm, Residual

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplastic Processes

Acute Lymphoblastic Leukemia

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Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Dexamethasone

Cytarabine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Methotrexate

Prednisone

Vincristine

Daunorubicin

Dexamethasone acetate

Pegaspargase

Mercaptopurine

Asparaginase

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antiviral Agents

Folinic Acid

Folate

Vitamin B9

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.

Vincristin

Peg-asparaginase

MTX 12 mg, Dexamethasone 2 mg, Cytarabine 60 mg D1, D8, D15, D22, D29

Intrathecal Suspension

75 mg/m2 D36 to D39, D43 to D46, D50 to D53 and D57 to D60

30 mg/m2 D36 to D63 and D1 to D56 of consolidation

Graziela Silva

Bruna Moraes, MSc

Wellington F Silva, MD PhD

Eduardo M Rego, MD PhD

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.

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.

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.

Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil

Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil - a Prospective Collaborative Study

cumulative proportion of patients alive (considering the time between the date of diagnosis and death or last follow-up)

time between enrollment in the study and the occurrence of any event: refractoriness after the first two cycles of induction, death or relapse.

proportion of patients who died before the first bone marrow evaluation of response (after induction I)

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

rate of disease relapse after CR calculated considering death as a competing event.

proportion of patients eligible for the protocol who were able to perform the procedure in their first CR

Servier

Instituto do Cancer do Estado de São Paulo

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil	NCT05959720	Acute Lymphoid ... Minimal Residua... Gene Abnormalit... Chemotherapeuti...	Prednisone Vincristin Daunorubicin Peg-asparaginas... Intrathecal Sus... Cyclophosphamid... Cytarabine Mercaptopurine Methotrexate Doxorubicin	16 Years - 50 Years	Instituto do Cancer do Estado de São Paulo
Adult Acute Lymphoblastic Leukemia Treated With Pediatric Regimen in Brazil	NCT05959720	Acute Lymphoid ... Minimal Residua... Gene Abnormalit... Chemotherapeuti...	Prednisone Vincristin Daunorubicin Peg-asparaginas... Intrathecal Sus... Cyclophosphamid... Cytarabine Mercaptopurine Methotrexate Doxorubicin	16 Years - 50 Years	Instituto do Cancer do Estado de São Paulo

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