Treatment of High Risk Adult Acute Lymphoblastic Leukemia

Condition(s) targeted: Acute Lymphoblastic Leukemia

Intervention: Vincristine (Drug); Daunorubicin (Drug); Prednisone (Drug); Mitoxantrone (Drug); Cytosine Arabinoside (Drug); Dexamethasone (Drug); Methotrexate (MTX) (Drug); Cytarabine (Drug); ASP (Drug); Mercaptopurine (Drug); Teniposide (Drug); Hydrocortisone (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: PETHEMA Foundation

Official(s) and/or principal investigator(s):
Ribera Josep Mª, Dr, Study Chair, Affiliation: PETHEMA Foundation

Overall contact:
Ribera Josep Mª, DR, Email: jribera@iconcologia.net

Current therapeutic protocols for adult ALL consider MRD together with the baseline risk factors (age, WBC count, immunophenotype, cytogenetics) and speed in response to therapy for treatment decisions. On the other hand, the systematic use of allogeneic SCT for all adult patients (pts) with Ph- HR-ALL is still a matter of debate. The aim of the prospective study ALL-AR-03 from the Spanish PETHEMA Group was to evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels (assessed by cytofluorometry at the end of induction and consolidation therapy) in HR Ph- adult ALL patients.

Official title: Treatment of High Risk Adult Acute Lymphoblastic Leukemia

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: To evaluate the response to a differentiated therapy (chemotherapy or allogeneic SCT) according to early bone marrow blast clearance and MRD levels in HR Ph- adult ALL patients.

Detailed description: HR ALL included one or more of the following baseline parameters: age 30-60 yr, WBC count >25x109/L and 11q23 or MLL rearrangements. Induction therapy included vincristine, prednisone and daunorubicin for 4 weeks. In pts with slow cytologic response to therapy (≥10% blasts in bone marrow assessed on d14) intensified induction with high dose ARA-C and mitoxantrone was administered. Early consolidation therapy included 3 cycles with rotating cytotoxic drugs including high-dose methotrexate, high-dose ARA-C and high-dose asparaginase. Pts. with slow cytologic response on d14 or MRD level >0. 05% after consolidation were assigned to allogeneic SCT (related or unrelated) and those with standard cytologic response on d14 and MRD level <0. 05% after consolidation received 3 additional cycles of delayed consolidation (identical to those of early consolidation) followed by maintenance therapy up to 2yr in CR.

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- High risk ALL adult patients (age> 15 years)no treated previously

- High-risk ALL:

- One or more of the following:

- Age 30-60 yr.

- WBC count >25x109/L

- 11q23 or ALL1/AF4

- Very high-risk ALL:

- HR ALL and one or the following:

- Slow cytologic response (>10% blasts in BM on d14 of induction therapy).

- MRD>0. 05% (by flow cytometry) at the end of consolidation

Exclusion Criteria:

- L3 ALL or B mature(sIg +) or t(8;14), t(2;8), t(8;22).

- ALL Ph (BCR/ABL) positive.

- Bifenotipics ALL as EGIL criteria.

- Indifferentiated ALL.

- Patients with cardiac pathology

- Patients with chronic liver disease in activity fase

- Pulmonary disease

- Renal insufficiency not due to ALL

- Neurological disorders not due to ALL

- PS (grades 3 and 4) not due to ALL.

Ribera Josep Mª, DR, Email: jribera@iconcologia.net

Hospital General, Alicante, Spain; Recruiting

Hospital Germans Trias i Pujol, Badalona, Spain; Recruiting
Ribera Josep Mª, Dr
Ribera Josep Mª, Dr, Principal Investigator

Hospital Duran y Reynals, Barcelona, Spain; Recruiting

Hospital de Sant Pau, Barcelona, Spain; Recruiting
Brunet Salut, Dr
Salut Brunet, Dr, Principal Investigator

Hospital Vall d'Hebrón, Barcelona, Spain; Recruiting

Clínica Teknon, Barcelona, Spain; Recruiting

Hospital Clínic i Provincial, Barcelona, Spain; Recruiting
Esteve Jordi, Dr
Esteve Jordi, Dr, Principal Investigator

Hospital General, Castellón, Spain; Recruiting

Hospital San Pedro de Alcántara, Cáceres, Spain; Recruiting

Hospital Puerta del Mar, Cádiz, Spain; Recruiting

Hospital Josep Trueta, Girona, Spain; Recruiting

Hospital Universitario, Guadalajara, Spain; Recruiting

Hospital Juan Canalejo, La Coruña, Spain; Recruiting

Hospital Xeral, Lugo, Spain; Recruiting

Hospital Clínico Universitario, Madrid, Spain; Recruiting

Hospital de Fuenlabrada, Madrid, Spain; Recruiting

Hospital 12 de Octubre, Madrid, Spain; Recruiting

Hospital Ramón y Cajal, Madrid, Spain; Recruiting

Hospital Morales Messeguer, Murcia, Spain; Recruiting

Hospital Carlos Haya, Málaga, Spain; Recruiting
Bethancourt Concepción, Dr
Bethancourt Concepción, Dr, Principal Investigator

Hospital Virgen de la Victoria, Málaga, Spain; Recruiting

Hospital Central de Asturias, Oviedo, Spain; Recruiting

Hospital Son Llàtzer, Palma de Mallorca, Spain; Recruiting

Clínica Universitaria de Navarra, Pamplona, Spain; Recruiting

Hospital Parc Taulí, Sabadell, Spain; Recruiting

Hospital Clínico Universitario, Salamanca, Spain; Recruiting

Hospital Marqués de Valdecilla, Santander, Spain; Recruiting

Hospital Xeral, Santiago, Spain; Recruiting

Hospital Virgen del Rocio, Sevilla, Spain; Recruiting
Parody Ricardo, Dr
Parody Ricardo, Dr, Principal Investigator

Hospital Joan XXIII, Tarragona, Spain; Recruiting

Hospital Mútua de Terrassa, Terrassa, Spain; Recruiting

Hospital Dr Pesset, Valencia, Spain; Recruiting

Hospital Clínico Universitario, Valencia, Spain; Recruiting

Hospital La Fe, Valencia, Spain; Recruiting
Sanz Miguel Angel, Principal Investigator

Hospital General, Valencia, Spain; Recruiting

Hospital Clínico, Valladolid, Spain; Recruiting

Hospital Virgen de la Concha, Zamora, Spain; Recruiting

Hospital Lozano Blesa, Zaragoza, Spain; Recruiting

Spanish Association of Hematology

Starting date: January 2003
Last updated: December 12, 2011