Treatment of Acute Lymphoblastic Leukemia HIGH RISK BCR / ABL NEGATIVE IN ADULTS

March 6, 2020 updated by: PETHEMA Foundation

Trial protocol intended the optimization of induction treatment with:

  1. Inclusion of PEG-ASP in induction and in the three blocks of consolidation.
  2. Reduction of the dose of daunorubicin, and recent studies have shown that the use of high doses of anthracyclines has not brought higher response rates or longer duration
  3. Replacing the poor cytological response at day 14 by the level of ER at the end of induction as a criterion to decide the further treatment (consolidation or second induction), so as to have only one criterion (the ER) throughout the study to decision making.

For another hand, reducing non-essential drugs consolidation blocks to try to reduce toxicity during it, and replace the ASP E. coli in induction and consolidation of PEG-ASP to ensure a more sustained asparagine depletion. Also, increasing the dose of methotrexate (3 to 5 g/m2) in patients with ALL-T, since there is recent evidence of a higher response rate with this strategy.

Performing an allo-HSCT early (after one cycle of consolidation) for patients with inadequate level of ER after two cycles of induction or in those patients who required two courses of induction and have obtained proper ER after the second.

Conducting studies of RD centrally by cytofluorometry following Euroflow consensus standards, to avoid bias in making treatment decisions

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

418

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Barcelona
      • Badalona, Barcelona, Spain
        • Hospital Germans Trias i Pujol

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

ALL patients

Description

Inclusion Criteria:

  • ALL de novo high-risk criteria
  • Age 15-55 years (55-60 years patients will be included at the discretion of the medical team that will attend)
  • No prior treatment, except Emergency leukapheresis Emergency treatment of hyperleukocytosis with hydroxyurea Urgent cranial irradiation (one dose) for CNS leukostasis Mediastinal irradiation for urgent superior vena cava syndrome
  • General condition suitable scale (ECOG 0-2), or> 2 if due to ALL
  • Negative pregnancy test for women of childbearing age
  • Written informed consent because, although the protocol does not include the use of investigational drugs, biological samples sent there for them

Exclusion Criteria:

  • L3 type ALL or mature phenotype B (sIg +) or cytogenetic abnormalities characteristic of mature B-ALL (t (8; 14), t (2, 8), t (8; 22)). For these patients is available BURKIMAB protocol.
  • LAL Ph (BCR-ABL) positive. For these patients have the protocol ALL-Ph-08 (if under 55) or LALOPh (if over 55).
  • Lymphoid blast crisis of chronic myeloid leukemia
  • Biphenotypic acute leukemia or bilinear according to the criteria of EGIL group
  • Undifferentiated acute leukemias
  • Patients with a history of coronary artery disease, valvular or hypertensive heart disease, contraindicating the use of anthracyclines
  • Patients with chronic phase of activity
  • Patients with severe chronic respiratory failure
  • Kidney failure due to ALL
  • Serious neurological disorder not due to the LAL
  • History of pancreatitis
  • Pregnancy or breastfeeding
  • Mental or psychiatric illness preventing informed consent is given for sending samples or properly follow the study
  • General condition affected, not attributable to the ALL

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
V + Dauno+ Pred+ Metot+ Cyta+ Hc + Ida + Flud
Vincristine in induction:5 mg/m2 i.v. days 1, 8, 15 and 22 in induction phase Daunorubicin in induction 45 mg/m2 i.v. days 1, 8, 15 and 22 Prednisone in induction: 60 mg/m2/ day, i.v. o p.o., days 1 to 14; 30 mg/m2/day, i.v. o p.o., days 15 to 21; 15 mg/m2/day i.v. o p.o., days 21 to 28 Metotrexato 12 mg days 1 and 22 (intrathecal) Cytarabine (ARA-C): 30 mg days 1 and 22 (intrathecal) Hydrocortisone: 20 mg days 1 and 22 (intrathecal) Idarubicin-induction 2 12 mg/m2, i.v., days 1, 3 and 5 Fludarabine in induction-2: Fludarabine 30 mg/m2, i.v., days, 1 to 5
Drug: Vincristine in induction
Drug: Daunorubicin in induction
Drug: Prednisone in induction
Drug: Metotrexato in induction
Drug: Cytarabine in induction
Drug: Hydrocortisone in induction
Drug: Idarubicin in induction-2
Drug: Fludarabine in induction-2
Drug: Ara-C in induction-2
Drug: G-CSF in induction-2
Drug: Dexamethasone in consolidation-1
Drug: Vincristrine in consolidation-1
Drug: Metotrexato in consolidation-1
Drug: PEG-ASP in consolidation-1
Drug: Dexamethasone in consolidation-2
Drug: ARA-C in consolidation-2
Drug: PEG-ASP in consolidation-2
Drug: Dexamethasone in consolidation-3
Drug: Vincristine in consolidation-3
Drug: Metotrexato in consolidation-3
Drug: PEG-ASP in consolidation-3
Procedure: allogeneic HSCT
Procedure: Allo HSCT with reduced-intensity conditioning

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate
Time Frame: 2 years
Improve the results of the protocol ALL-AR-03 with modifications in the study methodology of residual disease: centralized, Biomed protocols and the cut-off - <0.01% - internationally accepted and changes in the induction and consolidation treatment, without altering the overall design
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 5 years
5 years
Evaluate CR rate with addition of PEG-ASP in the induction phase
Time Frame: 2 years
2 years
Standarization of minimal residual disease
Time Frame: 2 years
Determination of minimal residual disease in a central laboratory trying to homogenice the results
2 years
To assess the toxic mortality
Time Frame: 2 years
To assess whether the reduction of daunorubicin in induction and changes in the consolidation drugs reduce toxic mortality in patients in complete remission
2 years
Assess the proportion of non-responders or slow responders
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PETHEMA Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2012

Primary Completion (Actual)

November 20, 2019

Study Completion (Actual)

December 1, 2019

Study Registration Dates

First Submitted

February 23, 2012

First Submitted That Met QC Criteria

February 23, 2012

First Posted (Estimate)

February 29, 2012

Study Record Updates

Last Update Posted (Actual)

March 9, 2020

Last Update Submitted That Met QC Criteria

March 6, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LAL-AR/2011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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