Treatment of High Risk Adult Acute Lymphoblastic Leukemia

NCT ID: NCT00853008

Last Updated: 2020-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2012-12-31

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.

Conditions

Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Vincristine

Vincristine (VCR): 1.5 mg/m2 (max 2 mg) IV d 1, 8, 15, 22 in induction VCR 2 mg, IV, d 1,8 in consolidation (cycle 1, 2)

Intervention Type: DRUG

Daunorubicin

Daunorubicin (DNR): 60 mg/m2 IV d 1, 8, 15, 22

Intervention Type: DRUG

Prednisone

Prednisone (PDN): 60 mg/m2/d IV or PO, d 1-28

Intervention Type: DRUG

Mitoxantrone

Mitoxantrone:12 mg/m2, IV d 15-17 in induction 12 mg/m2, IV,d 5 in cycle 2 consolidation

Intervention Type: DRUG

Cytosine Arabinoside

ARA-C 2,000 mg/m2/12h IV, d18,19 (4 doses) in induction

Intervention Type: DRUG

Dexamethasone

Dexamethasone 20 mg/m2,IV, d 1-5,10 mg/m2,IV, d 6 and 5 mg/m2,IV, d 7 in Consolidation (3 cycles)

Intervention Type: DRUG

Methotrexate (MTX)

Methotrexate (MTX)3 g/m2,IV, d1 (24h)in consolidation, cycles 1 and 2 MTX (15 mg/m2/wk, IM)in maintenance MTX 15 mg, IT

Intervention Type: DRUG

Cytarabine

Cytarabine 2g/m2/12h, IV d5 in cycle 1 consolidation Cytarabine 2g/m2/12h, IV d 1,2 in cycle 3 consolidation Cytarabine 30 mg, intrathecal

Intervention Type: DRUG

ASP

ASP 25,000 IU/m2, IV, d5 in consolidation (cycle 1, 2, 3)

Intervention Type: DRUG

Mercaptopurine

Mercaptopurine 100 mg/m2, PO, d 1-5 in consolidation

Intervention Type: DRUG

Teniposide

Teniposide 150 mg/m2, IV d 3,4 in consolidation cycle 3

Intervention Type: DRUG

Hydrocortisone

Hydrocortisone 20 mg, IT d 1, 28, 49, 77, 105, 175, 203, 231, 259,287, 311 intrathecal

Intervention Type: DRUG

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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PETHEMA Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ribera Josep Mª, Dr

Role: STUDY_CHAIR

PETHEMA Foundation

Locations

Hospital Juan Canalejo

A Coruña, , Spain

Hospital General

Alicante, , Spain

Hospital Germans Trias i Pujol

Badalona, , Spain

Clínica Teknon

Barcelona, , Spain

Hospital Clínic i Provincial

Barcelona, , Spain

Hospital de Sant Pau

Barcelona, , Spain

Hospital Duran y Reynals

Barcelona, , Spain

Hospital Vall d'Hebrón

Barcelona, , Spain

Hospital Puerta del Mar

Cadiz, , Spain

Hospital General

Castellon, , Spain

Hospital San Pedro de Alcántara

Cáceres, , Spain

Hospital Josep Trueta

Girona, , Spain

Hospital Universitario

Guadalajara, , Spain

Hospital Xeral

Lugo, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Hospital Clínico Universitario

Madrid, , Spain

Hospital de Fuenlabrada

Madrid, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Hospital Carlos Haya

Málaga, , Spain

Hospital Virgen de la Victoria

Málaga, , Spain

Hospital Morales Messeguer

Murcia, , Spain

Hospital Central de Asturias

Oviedo, , Spain

Hospital Son Llàtzer

Palma de Mallorca, , Spain

Clínica Universitaria de Navarra

Pamplona, , Spain

Hospital Parc Taulí

Sabadell, , Spain

Hospital Clínico Universitario

Salamanca, , Spain

Hospital Marqués de Valdecilla

Santander, , Spain

Hospital Xeral

Santiago, , Spain

Hospital Virgen del Rocio

Seville, , Spain

Hospital Joan XXIII

Tarragona, , Spain

Hospital Mútua de Terrassa

Terrassa, , Spain

Hospital Clínico Universitario

Valencia, , Spain

Hospital Dr Pesset

Valencia, , Spain

Hospital General

Valencia, , Spain

Hospital La Fe

Valencia, , Spain

Hospital Clínico

Valladolid, , Spain

Hospital Virgen de la Concha

Zamora, , Spain

Hospital Lozano Blesa

Zaragoza, , Spain

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 24752047 (View on PubMed)

Related Links

http://aehh.org

Spanish Association of Hematology

Other Identifiers

LAL-AR/2003

Identifier Type: -

Identifier Source: org_study_id