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

Acute Lymphoblastic Leukemia Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01540812
• Other study ID #: LAL-AR/2011
• Status: Completed
• Start date: February 2012
• Est. completion date: December 1, 2019

Study information

• Verified date: March 2020
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 418
• Est. completion date: December 1, 2019
• Est. primary completion date: November 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Vincristine in induction

• Daunorubicin in induction

• Prednisone in induction

• Metotrexato in induction

• Cytarabine in induction

• Hydrocortisone in induction

• Idarubicin in induction-2

• Fludarabine in induction-2

• Ara-C in induction-2

• G-CSF in induction-2

• Dexamethasone in consolidation-1

• Vincristrine in consolidation-1

• Metotrexato in consolidation-1

• PEG-ASP in consolidation-1

• Dexamethasone in consolidation-2

• ARA-C in consolidation-2

• PEG-ASP in consolidation-2

• Dexamethasone in consolidation-3

• Vincristine in consolidation-3

• Metotrexato in consolidation-3

• PEG-ASP in consolidation-3

Procedure:
• allogeneic HSCT

• Allo HSCT with reduced-intensity conditioning

Locations

Country	Name	City	State
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

Outcome

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

External Links

•   Pethema Foundation web