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

NCT ID: NCT01540812

Last Updated: 2020-03-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

418 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-02-29

Study Completion Date

2019-12-01

Brief Summary

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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

Detailed Description

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Conditions

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Acute Lymphoblastic Leukemia

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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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

Vincristine in induction

Intervention Type DRUG

Daunorubicin in induction

Intervention Type DRUG

Prednisone in induction

Intervention Type DRUG

Metotrexato in induction

Intervention Type DRUG

Cytarabine in induction

Intervention Type DRUG

Hydrocortisone in induction

Intervention Type DRUG

Idarubicin in induction-2

Intervention Type DRUG

Fludarabine in induction-2

Intervention Type DRUG

Ara-C in induction-2

Intervention Type DRUG

G-CSF in induction-2

Intervention Type DRUG

Dexamethasone in consolidation-1

Intervention Type DRUG

Vincristrine in consolidation-1

Intervention Type DRUG

Metotrexato in consolidation-1

Intervention Type DRUG

PEG-ASP in consolidation-1

Intervention Type DRUG

Dexamethasone in consolidation-2

Intervention Type DRUG

ARA-C in consolidation-2

Intervention Type DRUG

PEG-ASP in consolidation-2

Intervention Type DRUG

Dexamethasone in consolidation-3

Intervention Type DRUG

Vincristine in consolidation-3

Intervention Type DRUG

Metotrexato in consolidation-3

Intervention Type DRUG

PEG-ASP in consolidation-3

Intervention Type DRUG

allogeneic HSCT

Intervention Type PROCEDURE

Allo HSCT with reduced-intensity conditioning

Intervention Type PROCEDURE

Interventions

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Vincristine in induction

Intervention Type DRUG

Daunorubicin in induction

Intervention Type DRUG

Prednisone in induction

Intervention Type DRUG

Metotrexato in induction

Intervention Type DRUG

Cytarabine in induction

Intervention Type DRUG

Hydrocortisone in induction

Intervention Type DRUG

Idarubicin in induction-2

Intervention Type DRUG

Fludarabine in induction-2

Intervention Type DRUG

Ara-C in induction-2

Intervention Type DRUG

G-CSF in induction-2

Intervention Type DRUG

Dexamethasone in consolidation-1

Intervention Type DRUG

Vincristrine in consolidation-1

Intervention Type DRUG

Metotrexato in consolidation-1

Intervention Type DRUG

PEG-ASP in consolidation-1

Intervention Type DRUG

Dexamethasone in consolidation-2

Intervention Type DRUG

ARA-C in consolidation-2

Intervention Type DRUG

PEG-ASP in consolidation-2

Intervention Type DRUG

Dexamethasone in consolidation-3

Intervention Type DRUG

Vincristine in consolidation-3

Intervention Type DRUG

Metotrexato in consolidation-3

Intervention Type DRUG

PEG-ASP in consolidation-3

Intervention Type DRUG

allogeneic HSCT

Intervention Type PROCEDURE

Allo HSCT with reduced-intensity conditioning

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

15 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PETHEMA Foundation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Countries

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Spain

References

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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.

Reference Type DERIVED
PMID: 33150388 (View on PubMed)

Other Identifiers

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LAL-AR/2011

Identifier Type: -

Identifier Source: org_study_id

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