RWE of Pediatric-like Protocol for AYA Patients With Ph-negative ALL

Real-world Evidence of First-line Treatment With Pediatric-like Protocol for Adolescents and Young Adults Patients Diagnosed With Philadelphia-negative Acute Lymphoblastic Leukemia

This is a multicenter, observational real world clinical trial with prospective follow up that will evaluate the treatment outcome of adolescent and young patients with ph-negative acute lymphoblastic leukemia with first-line pediatric-like protocol in Argentina.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia, Adult
• Intervention / Treatment: Other: Evaluation of survival and toxicities in AYA Ph-negative ALL patients treating in first line depending on risk category.

Detailed Description

The purpose of this trial is to gather real world evidence of treatment outcomes and toxicities of AYA Ph-negative ALL patients in Argentina who receive pediatric-like treatment in first line.

The study primary endpoints are to evaluate survival (event free survival and overall survival) and toxicities of AYA Ph-negative ALL patients treating in first line with pediatric-like protocol depending on risk category.

Secondary endpoints are to evaluate survival in patients who underwent allogeneic transplantation in first remission, asparaginase toxicities, and assess central cerebrospinal fluid by flow cytometry.

Every ALL patient diagnosed in our institutions will follow our guidelines with respect to diagnosis procedures.

High-risk (HR) group was defined as presenting high risk cytogenetics/molecular findings and depending on the response achieved at different time points: bad response to prednisone at day 8, ≥ 10% blast in bone marrow on day 15, minimal residual disease (MRD) by flow cytometry ≥0.1% at day 33 and ≥0.01% at day 78 in bone marrow. No-high risk group was defined as those without any high-risk factor.

The chemotherapy regimen included pre-induction phase, induction (phase I and II), consolidation, re-intensification, central nervous system (CNS) prophylaxis and maintenance therapy or ASCT in first remission .

The initial pre-induction phase, where steroids were given for 7 days. Induction therapy, phase IA consisted of weekly vincristine and daunorubicin for 4 weeks, L-Asparaginase for 8 doses or peg-asparaginase for 2 doses and prednisone continuously for 4 weeks. Phase IB consisted cytarabine for 16 doses, cyclophosphamide for 1-2 doses and 6-mercaptopurine for 28 days.

The consolidation phase consisted of 4 doses of methotrexate and 6-mercaptopurine for 56 days for Non-High Risk patients (M phase) and two cycles of three different blocks of high dose multi chemotherapy for HR patients. Re-induction consisted in two phases similar to induction. According to risk and response to treatment, patients will be candidates to maintenance for 18 months or ASCT in first remission.

Minimal residual disease will be evaluated at least on day 33, 78, in consolidation and every thee months during maintenance treatment or previous to ASCT.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Paula Freigeiro; Phone Number: 5491140470052; Email: gatla.ar@gmail.com
• Study Contact Backup: Name: Luciana Ferrari, Dr.; Phone Number: 541148771000; Email: lferrari@fundaleu.org.ar

Study Locations

• Argentina
  • Caba, Argentina
    • Recruiting
    • Fundaleu
    • Contact: Luciana Ferrari, Dr.; Phone Number: 541148771000; Email: lferrari@fundaleu.org.ar
  • Entre Ríos
    • Paraná, Entre Ríos, Argentina
      • Recruiting
      • Instituto Privado de Hematologia y Hemoterapia
      • Contact: Pedro Negri Aranguren, Dr.
      • Sub-Investigator: Florencia Negri Aranguren, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All AYA (18-40 years old) with recent diagnosis of ph-negative ALL without previous treatment.

Description

Inclusion Criteria:

• Signature of the form consent for participation in the study
• Ph-negative ALL diagnosis without previous treatment.

Exclusion Criteria:

• ALL with mature B phenotype (sIg +) or with the cytogenetic alterations characteristic of ALL mature B (t (8,14), t (2, 8), t (8, 22)).
• Ph-positive ALL
• Acute leukemias of ambiguous lineage (undifferentiated or mixed phenotype).
• Patients with a history of coronary, valvular or hypertensive heart disease, that contraindicate the use of anthracyclines.
• Patients with chronic liver disease in the activity phase and / or Bilirubin> 2 mg / dl and / or transaminases 5 times the normal limit, not related to ALL.
• Patients with severe chronic respiratory failure.
• Renal failure and / or creatininemia> 2 mg / dl not related to ALL.
• Serious neurological disorders, not related to leukemic disease.
• General condition affected (grades 3 and 4), not attributable to ALL.
• Uncontrolled infection by HIV, HTLV-1, HBV, HCV.
• Patient not a candidate for treatment based on the criteria of the treating physician.
• Pregnant women will have to be evaluated by a multidisciplinary team and an ethics committee.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adolescents and young adults Ph-negative ALL patients in first-line; Adolescents and young adults patients (18-40 years old) with recent diagnosis of Ph-negative acute lymphoblastic leukemia who receive argentinian pediatric-like treatment depending on risk category.	Other: Evaluation of survival and toxicities in AYA Ph-negative ALL patients treating in first line depending on risk category.; Evaluation of survival (event free survival and overall survival) and toxicities in AYA Ph-negative ALL patients treating in first line with argentinian pediatric-like protocol depending on risk category.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate event free survival of AYA Ph-negative ALL patients treating in first line depending on risk category.	Evaluate event free survival of AYA Ph-negative ALL patients treating in first line with pediatric-like protocol depending on risk category.	36 months
Evaluate overall survival of AYA Ph-negative ALL patients treating in first line depending on risk category.	Evaluate overall survival of AYA Ph-negative ALL patients treating in first line with pediatric-like protocol depending on risk category.	36 months
Evaluate toxicities of AYA Ph-negative ALL patients treating in first line depending on risk category.	Evaluate toxicities of AYA Ph-negative ALL patients treating in first line with pediatric-like protocol depending on risk category.	36 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate survival in patients who underwent allogeneic transplantation in first remission	36 months
Evaluate asparaginase toxicities.	36 months
Assess central cerebrospinal fluid involvement by flow cytometry.	36 months

Collaborators and Investigators

• Sponsor: Grupo Argentino de Tratamiento de la Leucemia Aguda
• Investigators: Study Chair: Isolda Fernández, Dr., Grupo Argentino de Tratamiento de la Leucemia Aguda; Principal Investigator: Maria Moirano, Dr., Grupo Argentino de Tratamiento de la Leucemia Aguda; Principal Investigator: Luciana Ferrari, Dr., Grupo Argentino de Tratamiento de la Leucemia Aguda

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 18, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Acute Lymphoblastic Leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: GATLA 11-LLA Ph(-)-20 AYA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Share study protocol
• IPD Sharing Time Frame: The data will become available on June 2021, and will remain available until the end of the clinical trial.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No