Clinical trial NCT00853008: Treatment of High Risk Adult Acute Lymphoblastic Leukemia
Official title: Treatment of High Risk Adult Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Lymphoblastic Leukemia
Keywords: Acute Lymphoblastic Leukemia
High-Risk (HR)
Philadelphia Chromosome-Negative
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
First posted: 2009-02-27
Enrollment: 100
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Alicante
country: Spain
facility: Hospital General
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Clínica Teknon
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
city: Barcelona
country: Spain
facility: Hospital Duran y Reynals
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebrón
city: Castellón
country: Spain
facility: Hospital General
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Cádiz
country: Spain
facility: Hospital Puerta del Mar
city: Girona
country: Spain
facility: Hospital Josep Trueta
city: Guadalajara
country: Spain
facility: Hospital Universitario
city: La Coruña
country: Spain
facility: Hospital Juan Canalejo
city: Lugo
country: Spain
facility: Hospital Xeral
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Clínico Universitario
city: Madrid
country: Spain
facility: Hospital de Fuenlabrada
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Murcia
country: Spain
facility: Hospital Morales Messeguer
city: Málaga
country: Spain
facility: Hospital Carlos Haya
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llàtzer
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
city: Sabadell
country: Spain
facility: Hospital Parc Taulí
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
city: Santiago
country: Spain
facility: Hospital Xeral
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Tarragona
country: Spain
facility: Hospital Joan XXIII
city: Terrassa
country: Spain
facility: Hospital Mútua de Terrassa
city: Valencia
country: Spain
facility: Hospital Clínico Universitario
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
city: Zamora
country: Spain
facility: Hospital Virgen de la Concha
city: Zaragoza
country: Spain
facility: Hospital Lozano Blesa
Study officials:
affiliation: PETHEMA Foundation
name: Ribera Josep Mª, Dr
role: STUDY_CHAIR
References:
citation: Ribera JM, Oriol A, Morgades M, Montesinos P, Sarra J, Gonzalez-Campos J, Brunet S, Tormo M, Fernandez-Abellan P, Guardia R, Bernal MT, Esteve J, Barba P, Moreno MJ, Bermudez A, Cladera A, Escoda L, Garcia-Boyero R, Del Potro E, Bergua J, Amigo ML, Grande C, Rabunal MJ, Hernandez-Rivas JM, Feliu E. Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol. 2014 May 20;32(15):1595-604. doi: 10.1200/JCO.2013.52.2425. Epub 2014 Apr 21.