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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by PETHEMA Foundation
Sponsor:
Information provided by (Responsible Party):
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT01540812
First received: February 23, 2012
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

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


Condition Intervention Phase
Acute Lymphoblastic Leukemia
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
Phase 4

Study Type: Interventional
Study Design: Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Evaluate CR rate with addition of PEG-ASP in the induction phase [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Standarization of minimal residual disease [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Determination of minimal residual disease in a central laboratory trying to homogenice the results

  • To assess the toxic mortality [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Study Start Date: February 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Vincristine in induction
5 mg/m2 i.v. days 1, 8, 15 and 22 in induction phase
Drug: Vincristine in induction
Active Comparator: Daunorubicin in induction
45 mg/m2 i.v. days 1, 8, 15 and 22
Drug: Daunorubicin in induction
Active Comparator: 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
Drug: Prednisone in induction
Active Comparator: Metrotexato in induction
Metotrexato 12 mg days 1 and 22 (intrathecal)
Drug: Metotrexato in induction
Active Comparator: Cytarabine in induction
Cytarabine (ARA-C): 30 mg days 1 and 22 (intrathecal)
Drug: Cytarabine in induction
Active Comparator: Hydrocortisone in induction
Hydrocortisone: 20 mg days 1 and 22 (intrathecal)
Drug: Hydrocortisone in induction
Active Comparator: Idarubicin in induction-2
Idarubicin 12 mg/m2, i.v., days 1, 3 and 5
Drug: Idarubicin in induction-2
Active Comparator: Fludarabine in induction-2
Fludarabine 30 mg/m2, i.v., days, 1 to 5
Drug: Fludarabine in induction-2
Active Comparator: Ara-C in induction-2
Ara-C 2 g/m2, i.v., days 1 to 5
Drug: Ara-C in induction-2
Active Comparator: G-CSF in induction-2
G-CSF 300 µg/d, i.v. o s.c., days 1 to 5
Drug: G-CSF in induction-2
Active Comparator: Dexamethasone in consolidation-1
  • 20 mg/m2/day, p.o. o i.v. days 1-5
  • 10 mg/m2/day, p.o. o i.v., day 6
  • 5 mg/m2/day, p.o. o i.v., day 7
  • 2,5 mg/m2/day, p.o. o i.v., day 8
Drug: Dexamethasone in consolidation-1
Active Comparator: Vincristrine in consolidation-1
1,5 mg/m2/day, i.v., days 1 and 8
Drug: Vincristrine in consolidation-1
Active Comparator: Metotrexato in consolidation-1
3 g/m2, i.v in 24 h, day 1 in ALL B and 5 g/m2 in ALL T
Drug: Metotrexato in consolidation-1
Active Comparator: PEG-ASP in consolidation-1
2.000 U/m2 day 3
Drug: PEG-ASP in consolidation-1
Active Comparator: Dexamethasone in consolidation-2
  • 20 mg/m2/day, p.o. o i.v. days 1-5
  • 10 mg/m2/day, p.o. o i.v., day 6
  • 5 mg/m2/day, p.o. o i.v., day 7
  • 2,5 mg/m2/day, p.o. o i.v., day 8
Drug: Dexamethasone in consolidation-2
Active Comparator: ARA-C in consolidation-2
2 g/m2 every 12 h, in 3 h, days 1 and 2
Drug: ARA-C in consolidation-2
Active Comparator: PEG-ASP in consolidation-2
2.000 U/m2 day 3
Drug: PEG-ASP in consolidation-2
Active Comparator: Dexamethasone in consolidation-3
20 mg/m2/day, p.o. o i.v. days 1-5 10 mg/m2/day, p.o. o i.v., day 6 5 mg/m2/day, p.o. o i.v., day 7 2,5 mg/m2/day, p.o. o i.v., day 8
Drug: Dexamethasone in consolidation-3
Active Comparator: Vincristine in consolidation-3
1,5 mg/m2, i.v., days 1 and 8
Drug: Vincristine in consolidation-3
Active Comparator: Metotrexato in consolidation-3
3 g/m2, i.v in 24 h, day 1 in ALL B and 5 g/m2 in ALL T
Drug: Metotrexato in consolidation-3
Active Comparator: PEG-ASP in consolidation-3
2.000 U/m2 day 3
Drug: PEG-ASP in consolidation-3
Active Comparator: allogeneic HSCT Procedure: allogeneic HSCT
Active Comparator: Allo HSCT with reduced-intensity conditioning Procedure: Allo HSCT with reduced-intensity conditioning

  Eligibility

Ages Eligible for Study:   15 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01540812

Contacts
Contact: Josep Mª Ribera, Dr + 34 93 497 88 00 jmribera@iconcologia.com

Locations
Spain
Hospital Germans Trias i Pujol Recruiting
Badalona, Barcelona, Spain
Contact: Jose Mª Ribera, Dr       jmribera@iconcologia.com   
Sponsors and Collaborators
PETHEMA Foundation
  More Information

Additional Information:
No publications provided

Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT01540812     History of Changes
Other Study ID Numbers: LAL-AR/2011
Study First Received: February 23, 2012
Last Updated: November 19, 2013
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
Acute Lymphoblastic Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Methotrexate
Fludarabine phosphate
Fludarabine
Pegaspargase
Daunorubicin
Dexamethasone
Idarubicin
Prednisone
Vincristine
BB 1101
Dexamethasone acetate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Dexamethasone 21-phosphate
Hydrocortisone-17-butyrate
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014