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

Phase 4

• Conditions: Acute Lymphoblastic Leukemia

• Registration Number: NCT01358201
• Lead Sponsor: PETHEMA Foundation

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

Study Timeline

• Study Start: 2010-05
• Study First Submitted: 2011-05-18
• Study First Submitted QC: 2011-05-20
• Study First Posted: 2011-05-23
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-17
• Last Update Posted: 2022-01-19
• Primary Completion: 2022-12
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Efficacy in terms of response rate	5 years

Secondary Outcome Measures

Name	Time	Method
Efficacy in terms disease free survival	5 years
Efficacy in terms of global survival	10 years

Trial Locations

Locations (73)

Hospital de Alcorcón; 🇪🇸 Alcorcón, Spain

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Fundación Hospital Alcorcón; 🇪🇸 Alcorcón, Spain

Institut Català d'oncología; 🇪🇸 Barcelona, Spain

H. de Jerez; 🇪🇸 Jerez de la Frontera, Spain

Hospital La Paz; 🇪🇸 Madrid, Spain

Complejo Asistencial Son Dureta; 🇪🇸 Palma de Mallorca, Spain

Hospital La Fe; 🇪🇸 Valencia, Spain

H. Son Llatzer; 🇪🇸 Palma de Mallorca, Baleares, Spain

Consorci Sanitari de Terrassa; 🇪🇸 Terrassa, Barcelona, Spain

Clínica Universitaria de Navarra; 🇪🇸 Pamplona, Navarra, Spain

Complejo Hospitalario Universitario de Albacete; 🇪🇸 Albacete, Spain

Hospital General de Alicante; 🇪🇸 Alicante, Spain

Hospital Valle Hebrón; 🇪🇸 Barcelona, Spain

Hospital de Fuenlabrada; 🇪🇸 Madrid, Spain

Hospital Sta. Maria del Rosell; 🇪🇸 Murcia, Spain

Hospital Clinic y Provincial de Barcelona; 🇪🇸 Barcelona, Spain

Hoapital General; 🇪🇸 Alicante, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Complejo Hospitalario de Cáceres; 🇪🇸 Cáceres, Spain

Basurtuko Ospitalea; 🇪🇸 Basurto, Spain

Area Hospitalaria Juan Ramón Jimenez; 🇪🇸 Huelva, Spain

Hospital Médico Quirúrgico Ciudad de Jaén; 🇪🇸 Jaen, Spain

Hospital Juan Canalejo; 🇪🇸 La Coruña, Spain

Clínica La Concepción; 🇪🇸 Madrid, Spain

Complejo Hospitalario León; 🇪🇸 Leon, Spain

Hospital Arnau de Vilanova; 🇪🇸 Lleida, Spain

Complexo Hospitalario Xeral-Calde; 🇪🇸 Lugo, Spain

Clínica Puerta de Hierro; 🇪🇸 Madrid, Spain

Clínica Rúber; 🇪🇸 Madrid, Spain

Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Hospital 12 de Octubre. Madrid; 🇪🇸 Madrid, Spain

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Althaia, Xarxa Asistencial de Manresa; 🇪🇸 Manresa, Spain

Hospital Central de Asturias; 🇪🇸 Oviedo, Spain

Hospital General Morales Meseguer; 🇪🇸 Murcia, Spain

Hospital Morales Messeguer. Murcia; 🇪🇸 Murcia, Spain

Hospital del Río Carrión; 🇪🇸 Palencia, Spain

Complejo Hospitalario de Pontevedra_Hospital Montecelo; 🇪🇸 Pontevedra, Spain

Complejo Hospitalario de Pontevedra_Hospital Provincial; 🇪🇸 Pontevedra, Spain

Corporació Sanitaria Parc Taulí; 🇪🇸 Sabadell, Spain

Hospital Clinico Universitario; 🇪🇸 Salamanca, Spain

Hospital Clínico de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Clínico Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital General de Segovia; 🇪🇸 Segovia, Spain

Clínica Sant Camil; 🇪🇸 Sant Pere de Ribes, Spain

Hospital Joan XXIII; 🇪🇸 Tarragona, Spain

Hoaspital Marqués de Valdecilla; 🇪🇸 Santander, Spain

Hoapital La Fe; 🇪🇸 Valencia, Spain

Hospital Clínico de Valencia; 🇪🇸 Valencia, Spain

Hospital Clínico de Valladolid; 🇪🇸 Valladolid, Spain

Comarcal de Vinaros; 🇪🇸 Vinaros, Spain

Hospital Clinico Lozano Blesa; 🇪🇸 Zaragoza, Spain

Hospital Lozano Blesa. Zaragoza; 🇪🇸 Zaragoza, Spain

Hospital de Madrid, S.A.- Norte Hospital General; 🇪🇸 Madrid, Spain

. Hospital Clínico Universitario Virgen de la Victoria; 🇪🇸 Málaga, Spain

Fundación Hospital Sant Joan de Déu de Martorell; 🇪🇸 Martorell, Spain

Complejo Hospital Costa del Sol; 🇪🇸 Málaga, Spain

Hospital Carlos Haya; 🇪🇸 Málaga, Spain

Hospital Clínico de Valencia.; 🇪🇸 Valencia, Spain

Complejo Hospitalario Reina Sofía; 🇪🇸 Córdoba, Spain

Hospital de Cruces; 🇪🇸 Bilbao, Spain

H. Carlos Haya; 🇪🇸 Málaga, Spain

Complejo Hospitalario Universitario de Vigo; 🇪🇸 Vigo, Spain

Hospital de la Santa Creu i Sant Pau.; 🇪🇸 Barcelona, Spain

Hospital Clínic; 🇪🇸 Valencia, Spain

Hospital Dr Pesset; 🇪🇸 Valencia, Spain

Hospital General; 🇪🇸 Valencia, Spain

Complejo Hospitalario Universitario de Santiago; 🇪🇸 Santiago de Compostela, Spain

Complejo Hospitalario Regional Virgen del Rocío; 🇪🇸 Sevilla, Spain

Fundación Instituto Valenciano de Oncología; 🇪🇸 Valencia, Spain

Hospital Clínico San Carlos de Madrid; 🇪🇸 Madrid, Spain

Hospital de la Princesa; 🇪🇸 Madrid, Spain