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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01358201
• Other study ID #: PETHEMA LAL-07FRAIL
• Status: Recruiting
• Phase: Phase 4
• Start date: May 2010
• Est. completion date: December 2022

Study information

• Verified date: January 2022
• Source: PETHEMA Foundation
• Contact: Josep Mª Ribera, Dr
• Email: jribera[@]iconcologia.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• vINCRISTINE

• Dexamethasone

• Methotrexate

• Cytosine arabinoside

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy in terms of response rate		5 years
Secondary	Efficacy in terms disease free survival		5 years
Secondary	Efficacy in terms of global survival		10 years

External Links

•   Pethema Foundation