Clinical trial NCT01540812: Treatment of Acute Lymphoblastic Leukemia HIGH RISK BCR / ABL NEGATIVE IN ADULTS
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Lymphoblastic Leukemia
Keywords: Acute Lymphoblastic Leukemia
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
First posted: 2012-02-29
Enrollment: 418
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: ALL patients

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


Eligibility criteria: 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

Primary outcomes:
measure: Overall response rate
timeFrame: 2 years
Secondary outcomes:
measure: Evaluate CR rate with addition of PEG-ASP in the induction phase
timeFrame: 2 years
measure: Standarization of minimal residual disease
timeFrame: 2 years
measure: To assess the toxic mortality
timeFrame: 2 years
measure: Assess the proportion of non-responders or slow responders
timeFrame: 2 years
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
Study officials:
References:
citation: Ribera JM, Morgades M, Ciudad J, Montesinos P, Esteve J, Genesca E, Barba P, Ribera J, Garcia-Cadenas I, Moreno MJ, Martinez-Carballeira D, Torrent A, Martinez-Sanchez P, Monsalvo S, Gil C, Tormo M, Artola MT, Cervera M, Gonzalez-Campos J, Rodriguez C, Bermudez A, Novo A, Soria B, Coll R, Amigo ML, Lopez-Martinez A, Fernandez-Martin R, Serrano J, Mercadal S, Cladera A, Gimenez-Conca A, Penarrubia MJ, Abella E, Vall-Llovera F, Hernandez-Rivas JM, Garcia-Guinon A, Bergua JM, de Rueda B, Sanchez-Sanchez MJ, Serrano A, Calbacho M, Alonso N, Mendez-Sanchez JA, Garcia-Boyero R, Olivares M, Barrena S, Zamora L, Granada I, Lhermitte L, Feliu E, Orfao A. Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia. Blood. 2021 Apr 8;137(14):1879-1894. doi: 10.1182/blood.2020007311.