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

Conditions

Acute Lymphoblastic Leukemia

Keywords

Acute Lymphoblastic Leukemia

Brief summary

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

Josep‐María Ribera, Mireia Morgades, Juana Ciudad, Pau Montesinos, Jordi Esteve et al. (51 authors)

Blood2020-11-0580 citations

10.1182/blood.2020007311

Outcome of Adults with Relapsed T-Cell Acute Lymphoblastic Leukemia (T-ALL) Included in Minimal Residual Disease (MRD)-Oriented Trials

Josep‐María Ribera, Eduardo Cerello Chapchap, Mireia Morgades, Eulàlia Genescà, Cristina Gil et al. (25 authors)

Blood2020-11-04

10.1182/blood-2020-137383

Post-Remission Treatment with Chemotherapy or Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) in Adult Patients with High-Risk (HR) Philadelphia Chromosome-Negative (Ph-neg) Acute Lymphoblastic Leukemia (ALL) According to Their Minimal Residual Disease (MRD). Final Results of the Pethema ALL-HR-11 Trial

Josep‐María Ribera, Mireia Morgades, Juana Ciudad, Pau Montesinos, Pere Barba et al. (35 authors)

Blood2019-11-135 citations

10.1182/blood-2019-123613

Characteristics and Outcome of Early T Cell Precursor ALL (ETP-ALL) Patients Treated with High-Risk Spanish Pethema Protocols

Eulàlia Genescà, Mireia Morgades, Pau Montesinos, Pere Barba, Cristina Gil et al. (34 authors)

Blood2018-11-29

10.1182/blood-2018-99-114559

Interventions

DRUGVincristine in induction

DRUGDaunorubicin in induction

DRUGPrednisone in induction

DRUGMetotrexato in induction

DRUGCytarabine in induction

DRUGHydrocortisone in induction

DRUGIdarubicin in induction-2

DRUGFludarabine in induction-2

DRUGAra-C in induction-2

DRUGG-CSF in induction-2

DRUGDexamethasone in consolidation-1

DRUGVincristrine in consolidation-1

DRUGMetotrexato in consolidation-1

DRUGPEG-ASP in consolidation-1

DRUGDexamethasone in consolidation-2

DRUGARA-C in consolidation-2

DRUGPEG-ASP in consolidation-2

DRUGDexamethasone in consolidation-3

DRUGVincristine in consolidation-3

DRUGMetotrexato in consolidation-3

DRUGPEG-ASP in consolidation-3

PROCEDUREallogeneic HSCT

PROCEDUREAllo HSCT with reduced-intensity conditioning

Study design

Observational model

CASE_ONLY

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

15 Years to 60 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Overall response rate	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

Secondary

Measure	Time frame	Description
Evaluate CR rate with addition of PEG-ASP in the induction phase	2 years	—
Standarization of minimal residual disease	2 years	Determination of minimal residual disease in a central laboratory trying to homogenice the results
To assess the toxic mortality	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
Assess the proportion of non-responders or slow responders	2 years	—
Overall survival	5 years	—

Countries

Spain

Outcome results

None listed