Clinical trial NCT05127148: RWE of Pediatric-like Protocol for AYA Patients With Ph-negative ALL
Official title: Real-world Evidence of First-line Treatment With Pediatric-like Protocol for Adolescents and Young Adults Patients Diagnosed With Philadelphia-negative Acute Lymphoblastic Leukemia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Lymphoblastic Leukemia, Adult
Keywords: Acute Lymphoblastic Leukemia
Lead sponsor: Grupo Argentino de Tratamiento de la Leucemia Aguda
Sponsor class: OTHER
First posted: 2021-11-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All AYA (18-40 years old) with recent diagnosis of ph-negative ALL without previous treatment.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate event free survival of AYA Ph-negative ALL patients treating in first line depending on risk category.
timeFrame: 36 months
measure: Evaluate overall survival of AYA Ph-negative ALL patients treating in first line depending on risk category.
timeFrame: 36 months
measure: Evaluate toxicities of AYA Ph-negative ALL patients treating in first line depending on risk category.
timeFrame: 36 months
Secondary outcomes:
measure: Evaluate survival in patients who underwent allogeneic transplantation in first remission
timeFrame: 36 months
measure: Evaluate asparaginase toxicities.
timeFrame: 36 months
measure: Assess central cerebrospinal fluid involvement by flow cytometry.
timeFrame: 36 months
Other outcomes:
Locations:
city: Paraná
country: Argentina
facility: Instituto Privado de Hematologia y Hemoterapia
state: Entre Ríos
city: Caba
country: Argentina
facility: FUNDALEU
Study officials:
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: Maria Moirano, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: Isolda Fernández, Dr.
role: STUDY_CHAIR
affiliation: Grupo Argentino de Tratamiento de la Leucemia Aguda
name: Luciana Ferrari, Dr.
role: PRINCIPAL_INVESTIGATOR
References: