Clinical Trials /

PETHEMA LAL-07FRAIL: All Treatment In Fragile Patients Ph' Negative Over 55 Years

NCT01358201

Description:

The biological characteristics of the adult LAL, karyotypic and phenotypic particular, are fundamentally different from those of Acute Lymphoblastic Leukemia (ALL) children and, consequently, the results of treatment are substantially lower. Additionally, elderly patients tolerate the drugs considered relatively low-key in the management of the LAL and suffer more toxicity. Although the LAL is much more common in patients over 60 years of age than in younger adults, older adults with ALL are clearly underrepresented in prospective controlled studies. A good portion of elderly patients are not able to tolerate the intensity of the standard treatment applied to children or young adults and a significant portion of them receive only palliative or supportive treatment. The data in the literature relating specifically to the elderly population are scarce and most of them have obtained a stratification by age of study designed for young people (CALGB, GMALL, PETHEMA). To date, the group's recommendation was to treat PETHEMA the LAL-96RI protocol for elderly patients because this protocol less aggressive than those used in high-risk ALL. However, the development of inhibitors of tyrosine kinases LAL effective in Bcr / abl positive, a relatively common type of LAL in the older patient, requires a differentiated treat these patients. Moreover, analysis of data from patients treated so far with the LAL-96RI protocol has shown mediocre results even for LAL Bcr / abl negative. This analysis also showed a significant benefit in survival related to the reduction of treatment (removal of the L-asparaginase during induction and cyclophosphamide at the end of induction) attributed to a reduction in toxicity

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 4

Trial Eligibility

Document

Title

  • Brief Title: PETHEMA LAL-07FRAIL: All Treatment In Fragile Patients Ph' Negative Over 55 Years
  • Official Title: Treatment Protocol For All Fragile Patients Ph' Negative Over 55 Years

Clinical Trial IDs

  • ORG STUDY ID: PETHEMA LAL-07FRAIL
  • NCT ID: NCT01358201

Conditions

  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
vINCRISTINE
Dexamethasone
Methotrexate
Cytosine arabinoside

Purpose

The biological characteristics of the adult LAL, karyotypic and phenotypic particular, are fundamentally different from those of Acute Lymphoblastic Leukemia (ALL) children and, consequently, the results of treatment are substantially lower. Additionally, elderly patients tolerate the drugs considered relatively low-key in the management of the LAL and suffer more toxicity. Although the LAL is much more common in patients over 60 years of age than in younger adults, older adults with ALL are clearly underrepresented in prospective controlled studies. A good portion of elderly patients are not able to tolerate the intensity of the standard treatment applied to children or young adults and a significant portion of them receive only palliative or supportive treatment. The data in the literature relating specifically to the elderly population are scarce and most of them have obtained a stratification by age of study designed for young people (CALGB, GMALL, PETHEMA). To date, the group's recommendation was to treat PETHEMA the LAL-96RI protocol for elderly patients because this protocol less aggressive than those used in high-risk ALL. However, the development of inhibitors of tyrosine kinases LAL effective in Bcr / abl positive, a relatively common type of LAL in the older patient, requires a differentiated treat these patients. Moreover, analysis of data from patients treated so far with the LAL-96RI protocol has shown mediocre results even for LAL Bcr / abl negative. This analysis also showed a significant benefit in survival related to the reduction of treatment (removal of the L-asparaginase during induction and cyclophosphamide at the end of induction) attributed to a reduction in toxicity

Detailed Description

      Prephase (days -5 to -1) Dexamethasone 10 mg/m2 bolus day EV for 5 days (-5 to -1).
      Supplementary treatment: hydration minimum 2000 ml / day. allopurinol 300 mg / day. gastric
      protection (as center). daily monitoring of blood glucose daily monitoring of renal function.

      Intrathecal treatment (diagnosis and prophylactic / therapeutic) day -5: 12 mg were
      administered intrathecal methotrexate. The morphological study of the CSF will be defining
      initial CNS involvement by LAL. Although it is recommended immunophenotypic study of CSF, the
      definition of CNS involvement by LAL (and its therapeutic consequences) based on
      morphological observation of blasts in CSF cytocentrifuge.

      Remission induction :

      Tolerance prephase period can be used to establish the final indication of treatment
      (standard protocol or frail patients). Day 0 is free of treatment and is considered as +1 the
      first day of induction.

      Systemic treatment

        -  Vincristine (VCR) 1 mg (absolute dose) EV 1, 8, 15 and 22.

        -  Dexamethasone (DEX): 10 mg/m2 EV, IM or PO days 1-2, 8-9 days 15-16, 22-23.

      Intrathecal chemotherapy

      Triple therapy was administered with methotrexate (MTX), cytosine arabinoside (ARA-C) and
      hydrocortisone, days 1, 8, 15 and 22 (five doses total prophylactic between prephase and
      induction):

      MTX 12 mg ARA-C 40 mg Dexamethasone 4 mg

      If initial infiltration of the CNS is administered once every 72 hours until the
      disappearance of blast cell morphology CSF (cytocentrifugation) in at least two consecutive
      taps. Alternatively be administered liposomal cytarabine (DepoCyt) fortnightly if authorized
      by the center or in the context of a clinical trial

      Maintenance treatment of first year :

      Maintenance during the first year will start after full recovery after induction and after
      complete reassessment of the disease (including myelogram) and will last until one year from
      the time of documentation of complete remission.

      The basic treatment to include mercaptopurine 50 mg/m2 PO day and methotrexate 20 mg/m2 IM
      weekly.

      Once every 3 months will be added to maintenance treatment a "mini-reinduction" consisting

        -  VCR: 1 mg (absolute dose), i.v., day 1.

        -  Dexamethasone 40 mg / day, i.v. or p.o., days 1-2.

        -  Not considered more doses of triple intrathecal therapy. Reinduction only be practiced
           during the first year after remission, so a total of 4 quarterly.

      Maintenance of the second year:

      After the first year of maintenance will perform a complete reassessment of the disease
      (including myelogram) and if the patient remains in complete remission maintenance will
      continue (without reinduction) until two years from the time of diagnosis.

      The initial dose of mercaptopurine and methotrexate will be identical to the first year. Must
      comply (by increases or decreases of 20% of the dose) to maintain the numbers of neutrophil
      counts between 1.5 and 3x109/l and platelets above 100x109 / L
    

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

        Adults over 55 years diagnosed with acute lymphoblastic leukemia Ph 'negative and not
        previously treated with frailty (> 3 points in the Charlson comorbidity index)

        Exclusion Criteria:

        LAL

        1. L3 type mature B phenotype (sIg +) or cytogenetic abnormalities characteristic of
        Burkitt LAL (t [8, 14], t [2, 8], t [8, 22]).

        2 . biphenotypic acute leukemias and bilinear 3 . acute undifferentiated leukemia 4 .
        Patients with a Charlson comorbidity index less than or equal to 3 (and therefore that
        could potentially benefit from more intensive treatment PETHEMA LAL-07OLD).

        5 . General condition affected (grades 3 and 4 WHO scale), not attributable to the LAL.

        6 . LAL Ph 'positive (though still must register their LAL07OPH specific protocol).

        7 . Lack of consent by the patient to use their clinical data
      
Maximum Eligible Age:N/A
Minimum Eligible Age:55 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Efficacy in terms of response rate
Time Frame:5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Efficacy in terms disease free survival
Time Frame:5 years
Safety Issue:
Description:
Measure:Efficacy in terms of global survival
Time Frame:10 years
Safety Issue:
Description:

Details

Phase:Phase 4
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:PETHEMA Foundation

Trial Keywords

  • Acute Lymphoblastic Leukemia

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