Treatment of High Risk Adult Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

— LAL-AR/2003  

Official title:

Treatment of High Risk Adult Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00853008
• Other study ID #: LAL-AR/2003
• Status: Completed
• Phase: Phase 4
• Start date: January 2003
• Est. completion date: December 2012

Study information

• Verified date: April 2020
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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)
• Daunorubicin
Daunorubicin (DNR): 60 mg/m2 IV d 1, 8, 15, 22
• Prednisone
Prednisone (PDN): 60 mg/m2/d IV or PO, d 1-28
• Mitoxantrone
Mitoxantrone:12 mg/m2, IV d 15-17 in induction 12 mg/m2, IV,d 5 in cycle 2 consolidation
• Cytosine Arabinoside
ARA-C 2,000 mg/m2/12h IV, d18,19 (4 doses) in induction
• 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)
• 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
• 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
• ASP
ASP 25,000 IU/m2, IV, d5 in consolidation (cycle 1, 2, 3)
• Mercaptopurine
Mercaptopurine 100 mg/m2, PO, d 1-5 in consolidation
• Teniposide
Teniposide 150 mg/m2, IV d 3,4 in consolidation cycle 3
• Hydrocortisone
Hydrocortisone 20 mg, IT d 1, 28, 49, 77, 105, 175, 203, 231, 259,287, 311 intrathecal

Locations

Country	Name	City	State
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 San Pedro de Alcántara	Cáceres
Spain	Hospital Puerta del Mar	Cádiz
Spain	Hospital General	Castellón
Spain	Hospital Josep Trueta	Girona
Spain	Hospital Universitario	Guadalajara
Spain	Hospital Juan Canalejo	La Coruña
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	Sevilla
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

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		2 years

External Links

•   Spanish Association of Hematology