Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05959720
Other study ID # 3011/22
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date September 5, 2023
Est. completion date June 2030

Study information

Verified date September 2023
Source Instituto do Cancer do Estado de São Paulo
Contact Graziela Silva
Phone 551138934677
Email graziela.sasilva@hc.fm.usp.br
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 180
Est. completion date June 2030
Est. primary completion date June 2028
Accepts healthy volunteers No
Gender All
Age group 16 Years to 50 Years
Eligibility 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. Exclusion Criteria: - Burkitt leukemia - Prior myeloproliferative disease - Philadelphia chromosome positivity through whichever methodology (RT-PCR, FISH, or conventional karyotype) - ECOG>2 (appendix 3) - Total bilirubin>2x upper limit of normal (ULN) - Transaminases>5x ULN - Creatinine>2,5 mg/dl - Positive serology for HIV or HTLV - Heart failure NYHA Class III or IV (appendix 4) - Severe psychiatric disorder which prevents adequate compliance - Prior treatment with intravenous chemotherapy - Refusal to participate in the study - Down syndrome

Study Design


Intervention

Drug:
Prednisone
60 mg/m2 D1 to D21
Vincristin
1.5 mg/m2 D1, D8, D15 and D22
Daunorubicin
40 mg/m2 D1, D8, D15 and D22
Peg-asparaginase
2000 UI/m2 D12 and D26
Intrathecal Suspension
MTX 12 mg, Dexamethasone 2 mg, Cytarabine 60 mg D1, D8, D15, D22, D29
Cyclophosphamide
1000 mg/m2 D36 and D64
Cytarabine
75 mg/m2 D36 to D39, D43 to D46, D50 to D53 and D57 to D60
Mercaptopurine
30 mg/m2 D36 to D63 and D1 to D56 of consolidation
Methotrexate
3.000 mg/m2 D8, D22, D36 and D50
Doxorubicin
30 mg/m2 D1 and D22

Locations

Country Name City State
Brazil Instituto do Cancer do Estado de Sao Paulo São Paulo SP

Sponsors (2)

Lead Sponsor Collaborator
Instituto do Cancer do Estado de São Paulo Servier

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Overall survival (OS) cumulative proportion of patients alive (considering the time between the date of diagnosis and death or last follow-up) 4 years
Secondary Event-free survival (EFS) time between enrollment in the study and the occurrence of any event: refractoriness after the first two cycles of induction, death or relapse. 4 years
Secondary Early death rate proportion of patients who died before the first bone marrow evaluation of response (after induction I) 60 days
Secondary Complete response rate 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 60 days
Secondary Cumulative incidence of relapse rate of disease relapse after CR calculated considering death as a competing event. 4 years
Secondary HSCT rate proportion of patients eligible for the protocol who were able to perform the procedure in their first CR 2 years
See also
  Status Clinical Trial Phase
Completed NCT04277650 - System for High-Intensity Evaluation During Radiotherapy N/A
Recruiting NCT06041477 - Concurrently vs Sequentially Combined HAIC With Targeted and Immunotherapy in Potentially Resectable HCC Phase 3
Recruiting NCT06421610 - OPC5: Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) in Patients With Malignant Pleural Effusion. Phase 1
Recruiting NCT06012253 - The Effect of Home-Based Walking Program on Peripheral Neuropathy, Fatigue and Quality of Life N/A
Recruiting NCT06197581 - Safety Assessment of Concurrent Radiotherapy and Novel Systemic Therapy for Breast Cancer N/A
Not yet recruiting NCT04965532 - Residual Neuromuscular Block of Rocuronium in Chemotherapy Patients Under Sevoflurane Anesthesia N/A
Completed NCT04843410 - Effect of Exercise in the Management of Peripheral Neuropathy N/A
Enrolling by invitation NCT04027478 - Can Fasting Decrease the Side Effects of Chemotherapy? N/A
Terminated NCT04607668 - Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer (mCRC): Phase 3
Completed NCT05635929 - Oral Mucositis and Quality of Life With a Mucosa Topical Composition in Head & Neck Cancer Patients. N/A
Recruiting NCT06357871 - Role of Renal Biopsy in the Suspicion of Nephrotoxicity of Immunotherapy (Checkpoint Inhibitors) in Solid Cancer
Completed NCT02996201 - Electronic Patient Reporting of Side Effects to Chemotherapy: A Cluster Randomized Controlled Trial N/A
Completed NCT00292526 - Prevention of Chemotherapy-induced Cardiotoxicity in High-risk Patients Phase 4
Completed NCT04663178 - Foot Bath and Chemotherapy Induced Fatigue N/A
Recruiting NCT03191461 - Myocardial Perfusion and Fibrosis in Cancer Survivors
Recruiting NCT05251922 - Tolerance of Anti-Cancer Therapy in the Elderly
Not yet recruiting NCT06387901 - Investigating Paclitaxel Toxicity in Breast Cancer: The Roles of Physical Activity and Body Composition.
Recruiting NCT05892146 - Strategy Therapy on Cancer Therapy-Related Cardiac Dysfunction N/A
Not yet recruiting NCT05921149 - Fasting Mimicking Diet (FMD) in Conjunction With Chemotherapy in Advanced Ovarian Cancer N/A
Recruiting NCT05302336 - AC vs TC in Patients With HR-positive, HER2-negative Early Breast Cancer Phase 4