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

Sponsor

PETHEMA Foundation (Other)

Overall Status

Recruiting

CT.gov ID

NCT01358201

Collaborator

(none)

100

Enrollment

Locations

151

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia	Drug: vINCRISTINE Drug: Dexamethasone Drug: Methotrexate Drug: Cytosine arabinoside	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 1, 2010

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Outcome Measures

Primary Outcome Measures

Efficacy in terms of response rate [5 years]

Secondary Outcome Measures

Efficacy in terms disease free survival [5 years]
Efficacy in terms of global survival [10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

Contacts and Locations

Locations

	Site	City	State	Country
1	H. Son Llatzer	Palma de Mallorca	Baleares	Spain
2	Consorci Sanitari de Terrassa	Terrassa	Barcelona	Spain
3	Clínica Universitaria de Navarra	Pamplona	Navarra	Spain
4	Complejo Hospitalario Universitario de Albacete	Albacete		Spain
5	Fundación Hospital Alcorcón	Alcorcón		Spain
6	Hospital de Alcorcón	Alcorcón		Spain
7	Hoapital General	Alicante		Spain
8	Hospital General de Alicante	Alicante		Spain
9	Hospital General de Alicante	Alicante		Spain
10	Hospital Germans Trias i Pujol	Badalona		Spain
11	Hospital Clinic y Provincial de Barcelona	Barcelona		Spain
12	Hospital de la Santa Creu i Sant Pau.	Barcelona		Spain
13	Hospital del Mar	Barcelona		Spain
14	Hospital Valle Hebrón	Barcelona		Spain
15	Institut Català d'oncología	Barcelona		Spain
16	Basurtuko Ospitalea	Basurto		Spain
17	Hospital de Cruces	Bilbao		Spain
18	Complejo Hospitalario de Cáceres	Cáceres		Spain
19	Complejo Hospitalario Reina Sofía	Córdoba		Spain
20	Area Hospitalaria Juan Ramón Jimenez	Huelva		Spain
21	Hospital Médico Quirúrgico Ciudad de Jaén	Jaen		Spain
22	H. de Jerez	Jerez de la Frontera		Spain
23	Hospital Juan Canalejo	La Coruña		Spain
24	Complejo Hospitalario León	Leon		Spain
25	Hospital Arnau de Vilanova	Lleida		Spain
26	Complexo Hospitalario Xeral-Calde	Lugo		Spain
27	Clínica La Concepción	Madrid		Spain
28	Clínica Puerta de Hierro	Madrid		Spain
29	Clínica Rúber	Madrid		Spain
30	Fundación Jiménez Díaz	Madrid		Spain
31	Hospital 12 de Octubre. Madrid	Madrid		Spain
32	Hospital Clinico San Carlos	Madrid		Spain
33	Hospital Clínico San Carlos de Madrid	Madrid		Spain
34	Hospital de Fuenlabrada	Madrid		Spain
35	Hospital de la Princesa	Madrid		Spain
36	Hospital de Madrid, S.A.- Norte Hospital General	Madrid		Spain
37	Hospital La Paz	Madrid		Spain
38	Althaia, Xarxa Asistencial de Manresa	Manresa		Spain
39	Fundación Hospital Sant Joan de Déu de Martorell	Martorell		Spain
40	Hospital General Morales Meseguer	Murcia		Spain
41	Hospital Morales Messeguer. Murcia	Murcia		Spain
42	Hospital Sta. Maria del Rosell	Murcia		Spain
43	. Hospital Clínico Universitario Virgen de la Victoria	Málaga		Spain
44	Complejo Hospital Costa del Sol	Málaga		Spain
45	H. Carlos Haya	Málaga		Spain
46	Hospital Carlos Haya	Málaga		Spain
47	Hospital Central de Asturias	Oviedo		Spain
48	Hospital del Río Carrión	Palencia		Spain
49	Complejo Asistencial Son Dureta	Palma de Mallorca		Spain
50	Complejo Hospitalario de Pontevedra_Hospital Montecelo	Pontevedra		Spain
51	Complejo Hospitalario de Pontevedra_Hospital Provincial	Pontevedra		Spain
52	Corporació Sanitaria Parc Taulí	Sabadell		Spain
53	Hospital Clinico Universitario	Salamanca		Spain
54	Hospital Clínico de Salamanca	Salamanca		Spain
55	Hospital Clínico Universitario de Salamanca	Salamanca		Spain
56	Hospital Clínico Universitario de Salamanca	Salamanca		Spain
57	Clínica Sant Camil	Sant Pere de Ribes		Spain
58	Hoaspital Marqués de Valdecilla	Santander		Spain
59	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela		Spain
60	Hospital General de Segovia	Segovia		Spain
61	Complejo Hospitalario Regional Virgen del Rocío	Sevilla		Spain
62	Hospital Joan XXIII	Tarragona		Spain
63	Fundación Instituto Valenciano de Oncología	Valencia		Spain
64	Hoapital La Fe	Valencia		Spain
65	Hospital Clínico de Valencia.	Valencia		Spain
66	Hospital Clínico de Valencia	Valencia		Spain
67	Hospital Clínic	Valencia		Spain
68	Hospital Dr Pesset	Valencia		Spain
69	Hospital General	Valencia		Spain
70	Hospital La Fe	Valencia		Spain
71	Hospital Clínico de Valladolid	Valladolid		Spain
72	Complejo Hospitalario Universitario de Vigo	Vigo		Spain
73	Comarcal de Vinaros	Vinaros		Spain
74	Hospital Clinico Lozano Blesa	Zaragoza		Spain
75	Hospital Lozano Blesa. Zaragoza	Zaragoza		Spain