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

Treatment Protocol For All Fragile Patients Ph' Negative Over 55 Years

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

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Methotrexate; Drug: Dexamethasone; Drug: vINCRISTINE; Drug: Cytosine arabinoside

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

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Josep Mª Ribera, Dr; Email: jribera@iconcologia.net

Study Locations

• Spain
  • Albacete, Spain
    • Recruiting
    • Complejo Hospitalario Universitario de Albacete
    • Principal Investigator: Santiago José, Dr
  • Alcorcón, Spain
    • Recruiting
    • Hospital de Alcorcón
  • Alcorcón, Spain
    • Recruiting
    • Fundacion Hospital Alcorcon
    • Principal Investigator: Peñalver Francisco Javier, Dr
  • Alicante, Spain
    • Recruiting
    • Hospital General de Alicante
    • Contact: Fernández Abellán Pascual, Dr
    • Principal Investigator: Fernández Abellán Pascual, Dr
  • Alicante, Spain
    • Recruiting
    • Hoapital General
    • Contact: Fernández Abellán Pascual, Dr
  • Badalona, Spain
    • Recruiting
    • Hospital Germans Trias i Pujol
    • Contact: Ribera Josep Mª, Dr
    • Principal Investigator: Ribera Josep Mª, Dr
  • Barcelona, Spain
    • Recruiting
    • Hospital del Mar
  • Barcelona, Spain
    • Recruiting
    • Institut Catala d'Oncologia
    • Contact: Boqué Concha, Dr
    • Principal Investigator: Boqué Concha, Dr
  • Barcelona, Spain
    • Recruiting
    • Hospital Clinic y Provincial de Barcelona
  • Barcelona, Spain
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau.
  • Barcelona, Spain
    • Recruiting
    • Hospital Valle Hebrón
    • Principal Investigator: Bueno Javier, Dr
  • Basurto, Spain
    • Recruiting
    • Basurtuko Ospitalea
  • Bilbao, Spain
    • Recruiting
    • Hospital de Cruces
    • Principal Investigator: Amutio Díez Elena, Dr
  • Cáceres, Spain
    • Recruiting
    • Complejo Hospitalario de Cáceres
  • Córdoba, Spain
    • Recruiting
    • Complejo Hospitalario Reina Sofía
  • Huelva, Spain
    • Recruiting
    • Area Hospitalaria Juan Ramón Jimenez
  • Jaen, Spain
    • Recruiting
    • Hospital Médico Quirúrgico Ciudad de Jaén
    • Contact: Alcala Antonio, Dr
    • Principal Investigator: Alcalá Antonio, Dr
  • Jerez de la Frontera, Spain
    • Recruiting
    • H. de Jerez
    • Contact: José Luis Guzmán Zamudio, Dr
    • Principal Investigator: Guzmán Zamudio José Luis, Dr
  • La Coruña, Spain
    • Recruiting
    • Hospital Juan Canalejo
    • Contact: Deben Guillermo, Dr
    • Principal Investigator: Deben Guillermo, Dr
  • Leon, Spain
    • Recruiting
    • Complejo Hospitalario León
    • Principal Investigator: Fuertes Nuñez Marta, Dr
  • Lleida, Spain
    • Recruiting
    • Hospital Arnau De Vilanova
  • Lugo, Spain
    • Recruiting
    • Complexo Hospitalario Xeral-Calde
  • Madrid, Spain
    • Recruiting
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Recruiting
    • Hospital La Paz
    • Contact: Canales Miguel Ángel, Dr
    • Principal Investigator: Canales Miguel Angel, Dr
  • Madrid, Spain
    • Recruiting
    • Fundacion Jimenez Diaz
    • Principal Investigator: Prieto Elena, Dr
  • Madrid, Spain
    • Recruiting
    • Clínica La Concepción
  • Madrid, Spain
    • Recruiting
    • Clínica Puerta de Hierro
    • Principal Investigator: Krisnk Isabel, Dr
  • Madrid, Spain
    • Recruiting
    • Hospital 12 de Octubre. Madrid
  • Madrid, Spain
    • Recruiting
    • Hospital Clínico San Carlos de Madrid
  • Madrid, Spain
    • Recruiting
    • Hospital De Fuenlabrada
    • Contact: Hernández Rivas José Angel, Dr
    • Principal Investigator: Hernández Rivas José Angel, Dr
  • Madrid, Spain
    • Recruiting
    • Hospital De La Princesa
  • Madrid, Spain
    • Recruiting
    • Hospital de Madrid, S.A.- Norte Hospital General
  • Madrid, Spain
    • Recruiting
    • Clinica Ruber
    • Principal Investigator: Martínez Carmen, Dr
  • Manresa, Spain
    • Recruiting
    • Althaia, Xarxa Asistencial de Manresa
  • Martorell, Spain
    • Recruiting
    • Fundación Hospital Sant Joan de Déu de Martorell
    • Principal Investigator: Las Heras German, Dr
  • Murcia, Spain
    • Recruiting
    • Hospital Sta. Maria del Rosell
  • Murcia, Spain
    • Recruiting
    • Hospital General Morales Meseguer
  • Murcia, Spain
    • Recruiting
    • Hospital Morales Messeguer. Murcia
    • Contact: Amigo Mª Luz, Dr
    • Principal Investigator: Amigo Mª Luz, Dr
  • Málaga, Spain
    • Recruiting
    • Hospital Carlos Haya
  • Málaga, Spain
    • Recruiting
    • . Hospital Clínico Universitario Virgen de la Victoria
  • Málaga, Spain
    • Recruiting
    • Complejo Hospital Costa Del Sol
    • Contact: María Casanova Espinosa, Dr
    • Principal Investigator: Casanova Espinosa María, Dr
  • Málaga, Spain
    • Recruiting
    • H. Carlos Haya
    • Principal Investigator: Negri Silvia, Dr
  • Oviedo, Spain
    • Recruiting
    • Hospital Central de Asturias
    • Contact: Rayón MC, Dr
  • Palencia, Spain
    • Recruiting
    • Hospital del Río Carrión
  • Palma de Mallorca, Spain
    • Recruiting
    • Complejo Asistencial Son Dureta
    • Principal Investigator: Sampol Antonia
  • Pontevedra, Spain
    • Recruiting
    • Complejo Hospitalario de Pontevedra_Hospital Montecelo
  • Pontevedra, Spain
    • Recruiting
    • Complejo Hospitalario de Pontevedra_Hospital Provincial
    • Principal Investigator: Constela Manuel, Dr
  • Sabadell, Spain
    • Recruiting
    • Corporacio Sanitaria Parc Tauli
  • Salamanca, Spain
    • Recruiting
    • Hospital Clinico Universitario de Salamanca
    • Contact: Mateos Mª Victoria, Dr
    • Principal Investigator: Mateos Mª Victoria, Dr
    • Sub-Investigator: Mateo Gema, Dr
    • Sub-Investigator: García Sanz Ramón, Dr
  • Salamanca, Spain
    • Recruiting
    • Hospital Clínico de Salamanca
  • Salamanca, Spain
    • Recruiting
    • Hospital Clínico Universitario
    • Contact: Del Cañizo Consuelo, Dr
  • Sant Pere de Ribes, Spain
    • Recruiting
    • Clínica Sant Camil
    • Principal Investigator: Asensio Antonio, Dr
  • Santander, Spain
    • Recruiting
    • Hoaspital Marqués de Valdecilla
  • Santiago de Compostela, Spain
    • Recruiting
    • Complejo Hospitalario Universitario de Santiago
  • Segovia, Spain
    • Recruiting
    • Hospital General de Segovia
    • Principal Investigator: Hernández José Mariano
  • Sevilla, Spain
    • Recruiting
    • Complejo Hospitalario Regional Virgen del Rocío
  • Tarragona, Spain
    • Recruiting
    • Hospital Joan XXIII
  • Valencia, Spain
    • Recruiting
    • Hospital La Fe
  • Valencia, Spain
    • Recruiting
    • Hospital Clínico de Valencia.
  • Valencia, Spain
    • Recruiting
    • Hospital Clinic
  • Valencia, Spain
    • Recruiting
    • Hospital Dr Pesset
  • Valencia, Spain
    • Recruiting
    • Hospital Clinico de Valencia
    • Principal Investigator: Tormo Mar, Dr
  • Valencia, Spain
    • Recruiting
    • Fundación Instituto Valenciano de Oncología
    • Principal Investigator: Llorente Pablo, Dr
  • Valencia, Spain
    • Recruiting
    • Hoapital La Fe
    • Contact: Sanz Miguel Angel, Dr; Phone Number: 96 386 27 58; Email: msanz@uv.es
  • Valencia, Spain
    • Recruiting
    • Hospital General
    • Contact: Carbonell Félix, Dr
    • Principal Investigator: Carbonell Félix, Dr
  • Valladolid, Spain
    • Recruiting
    • Hospital Clínico de Valladolid
  • Vigo, Spain
    • Recruiting
    • Complejo Hospitalario Universitario de Vigo
  • Vinaros, Spain
    • Recruiting
    • Comarcal de Vinaros
    • Principal Investigator: Montagud Mario, Dr
  • Zaragoza, Spain
    • Recruiting
    • Hospital Clinico Lozano Blesa
    • Principal Investigator: Palomera Bernal Luis, Dr
  • Zaragoza, Spain
    • Recruiting
    • Hospital Lozano Blesa. Zaragoza
    • Contact: Olave Mª Teresa, Dr
    • Principal Investigator: Olave Mª Teresa, Dr
  • Baleares
    • Palma de Mallorca, Baleares, Spain
      • Recruiting
      • H. Son Llatzer
  • Barcelona
    • Terrassa, Barcelona, Spain
      • Recruiting
      • Consorci Sanitari de Terrassa
  • Navarra
    • Pamplona, Navarra, Spain
      • Recruiting
      • Clinica Universitaria De Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy in terms of response rate	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy in terms disease free survival	5 years
Efficacy in terms of global survival	10 years

Collaborators and Investigators

• Sponsor: PETHEMA Foundation

Publications and helpful links

Helpful Links

• Pethema Foundation

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2010
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: May 18, 2011
• First Submitted That Met QC Criteria: May 20, 2011
• First Posted (ESTIMATE): May 23, 2011

Study Record Updates

• Last Update Posted (ACTUAL): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Acute Lymphoblastic Leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Dexamethasone; Cytarabine; Methotrexate; Vincristine
• Other Study ID Numbers: PETHEMA LAL-07FRAIL