Clinical trial NCT01358201: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Lymphoblastic Leukemia
Keywords: Acute Lymphoblastic Leukemia
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
First posted: 2011-05-23
Enrollment: 100
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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

Primary outcomes:
measure: Efficacy in terms of response rate
timeFrame: 5 years
Secondary outcomes:
measure: Efficacy in terms disease free survival
timeFrame: 5 years
measure: Efficacy in terms of global survival
timeFrame: 10 years
Other outcomes:
Locations:
city: Palma de Mallorca
country: Spain
facility: H. Son Llatzer
state: Baleares
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
state: Navarra
city: Albacete
country: Spain
facility: Complejo Hospitalario Universitario de Albacete
city: Alcorcón
country: Spain
facility: Fundación Hospital Alcorcón
city: Alcorcón
country: Spain
facility: Hospital de Alcorcón
city: Alicante
country: Spain
facility: Hoapital General
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic y Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau.
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Valle Hebrón
city: Barcelona
country: Spain
facility: Institut Català d'oncología
city: Basurto
country: Spain
facility: Basurtuko Ospitalea
city: Bilbao
country: Spain
facility: Hospital de Cruces
city: Cáceres
country: Spain
facility: Complejo Hospitalario de Cáceres
city: Córdoba
country: Spain
facility: Complejo Hospitalario Reina Sofía
city: Huelva
country: Spain
facility: Area Hospitalaria Juan Ramón Jimenez
city: Jaen
country: Spain
facility: Hospital Médico Quirúrgico Ciudad de Jaén
city: Jerez de la Frontera
country: Spain
facility: H. de Jerez
city: La Coruña
country: Spain
facility: Hospital Juan Canalejo
city: Leon
country: Spain
facility: Complejo Hospitalario León
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Lugo
country: Spain
facility: Complexo Hospitalario Xeral-Calde
city: Madrid
country: Spain
facility: Clínica La Concepción
city: Madrid
country: Spain
facility: Clínica Puerta de Hierro
city: Madrid
country: Spain
facility: Clínica Rúber
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital 12 de Octubre. Madrid
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos de Madrid
city: Madrid
country: Spain
facility: Hospital de Fuenlabrada
city: Madrid
country: Spain
facility: Hospital de la Princesa
city: Madrid
country: Spain
facility: Hospital de Madrid, S.A.- Norte Hospital General
city: Madrid
country: Spain
facility: Hospital La Paz
city: Manresa
country: Spain
facility: Althaia, Xarxa Asistencial de Manresa
city: Martorell
country: Spain
facility: Fundación Hospital Sant Joan de Déu de Martorell
city: Murcia
country: Spain
facility: Hospital General Morales Meseguer
city: Murcia
country: Spain
facility: Hospital Morales Messeguer. Murcia
city: Murcia
country: Spain
facility: Hospital Sta. Maria del Rosell
city: Málaga
country: Spain
facility: . Hospital Clínico Universitario Virgen de la Victoria
city: Málaga
country: Spain
facility: Complejo Hospital Costa del Sol
city: Málaga
country: Spain
facility: H. Carlos Haya
city: Málaga
country: Spain
facility: Hospital Carlos Haya
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Palencia
country: Spain
facility: Hospital del Río Carrión
city: Palma de Mallorca
country: Spain
facility: Complejo Asistencial Son Dureta
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Pontevedra_Hospital Montecelo
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Pontevedra_Hospital Provincial
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Taulí
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario
city: Salamanca
country: Spain
facility: Hospital Clínico de Salamanca
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario de Salamanca
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario de Salamanca
city: Sant Pere de Ribes
country: Spain
facility: Clínica Sant Camil
city: Santander
country: Spain
facility: Hoaspital Marqués de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Segovia
country: Spain
facility: Hospital General de Segovia
city: Sevilla
country: Spain
facility: Complejo Hospitalario Regional Virgen del Rocío
city: Tarragona
country: Spain
facility: Hospital Joan XXIII
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hoapital La Fe
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia.
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Valencia
country: Spain
facility: Hospital Clínic
city: Valencia
country: Spain
facility: Hospital Dr Pesset
city: Valencia
country: Spain
facility: Hospital General
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico de Valladolid
city: Vigo
country: Spain
facility: Complejo Hospitalario Universitario de Vigo
city: Vinaros
country: Spain
facility: Comarcal de Vinaros
city: Zaragoza
country: Spain
facility: Hospital Clinico Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Lozano Blesa. Zaragoza
Study officials:
References: