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Treatment of High Risk Adult Acute Lymphoblastic Leukemia (LAL-AR/2003)

Primary Purpose

Acute Lymphoblastic Leukemia

Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Vincristine
Daunorubicin
Prednisone
Mitoxantrone
Cytosine Arabinoside
Dexamethasone
Methotrexate (MTX)
Cytarabine
ASP
Mercaptopurine
Teniposide
Hydrocortisone
Sponsored by
PETHEMA Foundation
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Acute Lymphoblastic Leukemia, High-Risk (HR), Philadelphia Chromosome-Negative

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • High risk ALL adult patients (age> 15 years)no treated previously
  • High-risk ALL:

  • One or more of the following:

    • Age 30-60 yr.
    • WBC count >25x109/L
    • 11q23 or ALL1/AF4
  • Very high-risk ALL:

  • HR ALL and one or the following:

    • Slow cytologic response (>10% blasts in BM on d14 of induction therapy).
    • MRD>0.05% (by flow cytometry) at the end of consolidation

Exclusion Criteria:

  • L3 ALL or B mature(sIg +) or t(8;14), t(2;8), t(8;22).
  • ALL Ph (BCR/ABL) positive.
  • Bifenotipics ALL as EGIL criteria.
  • Indifferentiated ALL.
  • Patients with cardiac pathology
  • Patients with chronic liver disease in activity fase
  • Pulmonary disease
  • Renal insufficiency not due to ALL
  • Neurological disorders not due to ALL
  • PS (grades 3 and 4) not due to ALL.

Sites / Locations

  • Hospital General
  • Hospital Germans Trias i Pujol
  • Clínica Teknon
  • Hospital Clínic i Provincial
  • Hospital de Sant Pau
  • Hospital Duran y Reynals
  • Hospital Vall d'Hebrón
  • Hospital General
  • Hospital San Pedro de Alcántara
  • Hospital Puerta del Mar
  • Hospital Josep Trueta
  • Hospital Universitario
  • Hospital Juan Canalejo
  • Hospital Xeral
  • Hospital 12 de Octubre
  • Hospital Clínico Universitario
  • Hospital de Fuenlabrada
  • Hospital Ramón y Cajal
  • Hospital Morales Messeguer
  • Hospital Carlos Haya
  • Hospital Virgen de la Victoria
  • Hospital Central de Asturias
  • Hospital Son Llàtzer
  • Clínica Universitaria de Navarra
  • Hospital Parc Taulí
  • Hospital Clínico Universitario
  • Hospital Marqués de Valdecilla
  • Hospital Xeral
  • Hospital Virgen del Rocio
  • Hospital Joan XXIII
  • Hospital Mútua de Terrassa
  • Hospital Clínico Universitario
  • Hospital Dr Pesset
  • Hospital General
  • Hospital La Fe
  • Hospital Clínico
  • Hospital Virgen de la Concha
  • Hospital Lozano Blesa

Outcomes

Primary Outcome Measures

To evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels in HR Ph- adult ALL patients.

Secondary Outcome Measures

Full Information

First Posted
February 25, 2009
Last Updated
April 6, 2020
Sponsor
PETHEMA Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00853008
Brief Title
Treatment of High Risk Adult Acute Lymphoblastic Leukemia
Acronym
LAL-AR/2003
Official Title
Treatment of High Risk Adult Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
January 2003 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PETHEMA Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Current therapeutic protocols for adult ALL consider MRD together with the baseline risk factors (age, WBC count, immunophenotype, cytogenetics) and speed in response to therapy for treatment decisions. On the other hand, the systematic use of allogeneic SCT for all adult patients (pts) with Ph- HR-ALL is still a matter of debate. The aim of the prospective study ALL-AR-03 from the Spanish PETHEMA Group was to evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels (assessed by cytofluorometry at the end of induction and consolidation therapy) in HR Ph- adult ALL patients.
Detailed Description
HR ALL included one or more of the following baseline parameters: age 30-60 yr, WBC count >25x109/L and 11q23 or MLL rearrangements. Induction therapy included vincristine, prednisone and daunorubicin for 4 weeks. In pts with slow cytologic response to therapy (≥10% blasts in bone marrow assessed on d14) intensified induction with high dose ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including high-dose methotrexate, high-dose ARA-C and high-dose asparaginase. Pts. with slow cytologic response on d14 or MRD level >0.05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level <0.05% after consolidation received 3 additional cycles of delayed consolidation (identical to those of early consolidation) followed by maintenance therapy up to 2yr in CR.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia
Keywords
Acute Lymphoblastic Leukemia, High-Risk (HR), Philadelphia Chromosome-Negative

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
Vincristine (VCR): 1.5 mg/m2 (max 2 mg) IV d 1, 8, 15, 22 in induction VCR 2 mg, IV, d 1,8 in consolidation (cycle 1, 2)
Intervention Type
Drug
Intervention Name(s)
Daunorubicin
Intervention Description
Daunorubicin (DNR): 60 mg/m2 IV d 1, 8, 15, 22
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone (PDN): 60 mg/m2/d IV or PO, d 1-28
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Intervention Description
Mitoxantrone:12 mg/m2, IV d 15-17 in induction 12 mg/m2, IV,d 5 in cycle 2 consolidation
Intervention Type
Drug
Intervention Name(s)
Cytosine Arabinoside
Intervention Description
ARA-C 2,000 mg/m2/12h IV, d18,19 (4 doses) in induction
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone 20 mg/m2,IV, d 1-5,10 mg/m2,IV, d 6 and 5 mg/m2,IV, d 7 in Consolidation (3 cycles)
Intervention Type
Drug
Intervention Name(s)
Methotrexate (MTX)
Intervention Description
Methotrexate (MTX)3 g/m2,IV, d1 (24h)in consolidation, cycles 1 and 2 MTX (15 mg/m2/wk, IM)in maintenance MTX 15 mg, IT
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
Cytarabine 2g/m2/12h, IV d5 in cycle 1 consolidation Cytarabine 2g/m2/12h, IV d 1,2 in cycle 3 consolidation Cytarabine 30 mg, intrathecal
Intervention Type
Drug
Intervention Name(s)
ASP
Intervention Description
ASP 25,000 IU/m2, IV, d5 in consolidation (cycle 1, 2, 3)
Intervention Type
Drug
Intervention Name(s)
Mercaptopurine
Intervention Description
Mercaptopurine 100 mg/m2, PO, d 1-5 in consolidation
Intervention Type
Drug
Intervention Name(s)
Teniposide
Intervention Description
Teniposide 150 mg/m2, IV d 3,4 in consolidation cycle 3
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Intervention Description
Hydrocortisone 20 mg, IT d 1, 28, 49, 77, 105, 175, 203, 231, 259,287, 311 intrathecal
Primary Outcome Measure Information:
Title
To evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels in HR Ph- adult ALL patients.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: High risk ALL adult patients (age> 15 years)no treated previously High-risk ALL: One or more of the following: Age 30-60 yr. WBC count >25x109/L 11q23 or ALL1/AF4 Very high-risk ALL: HR ALL and one or the following: Slow cytologic response (>10% blasts in BM on d14 of induction therapy). MRD>0.05% (by flow cytometry) at the end of consolidation Exclusion Criteria: L3 ALL or B mature(sIg +) or t(8;14), t(2;8), t(8;22). ALL Ph (BCR/ABL) positive. Bifenotipics ALL as EGIL criteria. Indifferentiated ALL. Patients with cardiac pathology Patients with chronic liver disease in activity fase Pulmonary disease Renal insufficiency not due to ALL Neurological disorders not due to ALL PS (grades 3 and 4) not due to ALL.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ribera Josep Mª, Dr
Organizational Affiliation
PETHEMA Foundation
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital General
City
Alicante
Country
Spain
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
Country
Spain
Facility Name
Clínica Teknon
City
Barcelona
Country
Spain
Facility Name
Hospital Clínic i Provincial
City
Barcelona
Country
Spain
Facility Name
Hospital de Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital Duran y Reynals
City
Barcelona
Country
Spain
Facility Name
Hospital Vall d'Hebrón
City
Barcelona
Country
Spain
Facility Name
Hospital General
City
Castellón
Country
Spain
Facility Name
Hospital San Pedro de Alcántara
City
Cáceres
Country
Spain
Facility Name
Hospital Puerta del Mar
City
Cádiz
Country
Spain
Facility Name
Hospital Josep Trueta
City
Girona
Country
Spain
Facility Name
Hospital Universitario
City
Guadalajara
Country
Spain
Facility Name
Hospital Juan Canalejo
City
La Coruña
Country
Spain
Facility Name
Hospital Xeral
City
Lugo
Country
Spain
Facility Name
Hospital 12 de Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Clínico Universitario
City
Madrid
Country
Spain
Facility Name
Hospital de Fuenlabrada
City
Madrid
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Hospital Morales Messeguer
City
Murcia
Country
Spain
Facility Name
Hospital Carlos Haya
City
Málaga
Country
Spain
Facility Name
Hospital Virgen de la Victoria
City
Málaga
Country
Spain
Facility Name
Hospital Central de Asturias
City
Oviedo
Country
Spain
Facility Name
Hospital Son Llàtzer
City
Palma de Mallorca
Country
Spain
Facility Name
Clínica Universitaria de Navarra
City
Pamplona
Country
Spain
Facility Name
Hospital Parc Taulí
City
Sabadell
Country
Spain
Facility Name
Hospital Clínico Universitario
City
Salamanca
Country
Spain
Facility Name
Hospital Marqués de Valdecilla
City
Santander
Country
Spain
Facility Name
Hospital Xeral
City
Santiago
Country
Spain
Facility Name
Hospital Virgen del Rocio
City
Sevilla
Country
Spain
Facility Name
Hospital Joan XXIII
City
Tarragona
Country
Spain
Facility Name
Hospital Mútua de Terrassa
City
Terrassa
Country
Spain
Facility Name
Hospital Clínico Universitario
City
Valencia
Country
Spain
Facility Name
Hospital Dr Pesset
City
Valencia
Country
Spain
Facility Name
Hospital General
City
Valencia
Country
Spain
Facility Name
Hospital La Fe
City
Valencia
Country
Spain
Facility Name
Hospital Clínico
City
Valladolid
Country
Spain
Facility Name
Hospital Virgen de la Concha
City
Zamora
Country
Spain
Facility Name
Hospital Lozano Blesa
City
Zaragoza
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
24752047
Citation
Ribera JM, Oriol A, Morgades M, Montesinos P, Sarra J, Gonzalez-Campos J, Brunet S, Tormo M, Fernandez-Abellan P, Guardia R, Bernal MT, Esteve J, Barba P, Moreno MJ, Bermudez A, Cladera A, Escoda L, Garcia-Boyero R, Del Potro E, Bergua J, Amigo ML, Grande C, Rabunal MJ, Hernandez-Rivas JM, Feliu E. Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol. 2014 May 20;32(15):1595-604. doi: 10.1200/JCO.2013.52.2425. Epub 2014 Apr 21.
Results Reference
derived
Links:
URL
http://aehh.org
Description
Spanish Association of Hematology

Learn more about this trial

Treatment of High Risk Adult Acute Lymphoblastic Leukemia

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