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

This study is currently recruiting participants.
Verified January 2017 by PETHEMA Foundation
Sponsor:
ClinicalTrials.gov Identifier:
NCT01540812
First Posted: February 29, 2012
Last Update Posted: January 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
PETHEMA Foundation
  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: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: 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 Outcome Measures:
  • Evaluate CR rate with addition of PEG-ASP in the induction phase [ Time Frame: 2 years ]
  • Standarization of minimal residual disease [ Time Frame: 2 years ]
    Determination of minimal residual disease in a central laboratory trying to homogenice the results

  • To assess the toxic mortality [ Time Frame: 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 [ Time Frame: 2 years ]
  • Overall survival [ Time Frame: 5 years ]

Estimated Enrollment: 200
Study Start Date: February 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
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

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
ALL patients
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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:
Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT01540812     History of Changes
Other Study ID Numbers: LAL-AR/2011
First Submitted: February 23, 2012
First Posted: February 29, 2012
Last Update Posted: January 12, 2017
Last Verified: January 2017

Keywords provided by PETHEMA Foundation:
Acute Lymphoblastic Leukemia

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Dexamethasone
Prednisone
Hydrocortisone
Fludarabine
Fludarabine phosphate
Pegaspargase
Cytarabine
Vincristine
Daunorubicin
Idarubicin
Asparaginase
Methotrexate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents