Chemotherapy and Imatinib in Young Adults With Acute Lymphoblastic Leukemia Ph (BCR-ABL) POSITIVE
1 other identifier
interventional
70
1 country
81
Brief Summary
20-25% of patients over 15 years with acute lymphoblastic leukemia (ALL) have the Philadelphia chromosome or BCR-ABL rearrangement. Traditionally, intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT) have formed the basis allogeneic treatment of this disease, but the results have been poor (60-75% complete remissions-RC-and probability of long-term survival less than 20%). The effectiveness of imatinib for hematologic responses in patients with Ph + (observed in phase I and II) led to its use in phase III trials in combination with chemotherapy. They saw a chance of obtaining the RC above 90%, with acceptable toxicity, a molecular response rate (MR) of 40-50%, and prolonged follow-up studies, a probability of disease-free survival (DFS ) of 30-50%, significantly higher than historical controls with the same chemotherapy without imatinib. This led to the approval of imatinib by the rating agencies in the U.S., Europe and Japan as a treatment for Ph + in combination with chemotherapy. Of the studies that led to the approval of this indication for imatinib, and other incurred after, the following conclusions can be drawn: There is no specific pattern of combination of imatinib (at doses of 600 mg / day, po) and chemotherapy. However, when compared with concomitant alternating with the first achieved a higher rate of RM at the end of induction, although this did not influence DFS. In studies in elderly patients has achieved a high CR rate (almost 100% in all series), only imatinib and glucocorticoids, suggesting that an attenuated induction may be sufficient to achieve CR in young patients with minimal toxicity, which further compromises the administration of treatment and allow for an allogeneic HSCT with minimal toxic load possible. Although there is no consensus on the indication of allogeneic HSCT in first CR when given imatinib associated with intensive chemotherapy is an option that is done in most studies. The allogeneic HSCT is most effective when carried out in complete molecular response to or greater than when there is more residual disease. However, the impact of MRI to obtain early (after induction) on survival is not clear. So far-reaching goal is to make the TPH in complete molecular response situation or greater. The relapse of the disease at the molecular level is still short-term (less than 3 months) of hematological relapse. This implies the need for frequent monitoring of residual disease (ER) The frequency of relapse post HSCT is high (around 30%), raising the need for any post HSCT treatment, including imatinib included. Are currently ongoing clinical trials comparing the systematic administration of imatinib after administration TPH face is detected only when ER. The applicability of the administration of imatinib after HSCT is limited by toxicity related to the procedure of TPH, is making frequent dose reduction or discontinuation. Therefore, a reasonable approximation treatment of Ph + outside the context of a clinical trial is to get as many molecular responses before allogeneic HSCT in a position to make the same MRI complete or greater. After TPH, must be very close monitoring of the ER, and imatinib is administered as soon as you notice the loss of molecular response. In patients who can not make an allogeneic HSCT for lack of histocompatible donor or contraindications for its realization it is recommended imatinib and chemotherapy, although there are studies that have undergone an autologous HSCT, followed or not treatment "maintenance" with imatinib. The low toxicity of autologous HSCT and no effect of graft versus leukemia are strongly recommended the administration of maintenance therapy with imatinib combined with chemotherapy or not.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_4
Started Jan 2008
Longer than P75 for phase_4
81 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2008
CompletedFirst Submitted
Initial submission to the registry
December 12, 2011
CompletedFirst Posted
Study publicly available on registry
December 14, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2022
CompletedJanuary 19, 2022
January 1, 2022
14.9 years
December 12, 2011
January 17, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Efficacy in terms of number of complete response
1 year
Interventions
600 mg p.o. from day 1 until consolidation
Eligibility Criteria
You may qualify if:
- Patients with Ph (BCR/ABL) positive de novo \< 55 years old (it is advisable to include patients over 55 years LAL07OPH protocol).
- Performance status 0-2 (Appendix B) may include patients with performance status \> 2 attributable to LAL.
- Patients without functional impairment of organs: liver function: total bilirubin, AST, ALT, alfa-GT and alkaline phosphatase less than 3 times the upper limit of normal laboratory renal function: serum creatinine \< 2 mg/dL or clearance creatinine \> 30 ml/min (except renal function attributable to LAL) cardiac function (Appendix B) normal: ventricular EF \> 50%, absence of severe chronic respiratory disease. In the event that alterations are secondary to the disease is at the discretion of the investigator to determine if the patient can be included in the trial.
You may not qualify if:
- Any other variety of LAL
- Patients with a history of coronary artery disease, valvular or hypertensive heart disease
- Patients with chronic liver disease
- Patients with chronic respiratory failure
- Renal failure not due to LAL
- Patients with positive HIV status
- No serious neurological abnormalities due to LAL
- Impact on overall severe (grade 3 or 4 of the WHO scale) not attributable to the LAL
- Pregnant or breastfeeding
- initial blast crisis CML
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (81)
H. Son Llatzer
Palma de Mallorca, Balearic Islands, Spain
Hospital Germans Trias i Pujol and all Hospital Pethema
Badalona, Barcelona, Spain
Hospital de Mataró
Mataró, Barcelona, Spain
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Canary Islands, Spain
Hospital general de Castellón
Castelló, Castellón, Spain
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, La Coruña, Spain
Clínica Universitaria de Navarra
Pamplona, Navarre, Spain
Hospital de Navarra
Pamplona, Navarre, Spain
Hospital Central de Asturias
Oviedo, Principality of Asturias, Spain
Hospital General de Albacete
Albacete, Spain
Hospital de Alcorcón
Alcorcón, Spain
Hospital General de Alicante.
Alicante, Spain
Hospital de Cabueñes
Asturias, Spain
Hospital de Badalona Germans Trias i Pujol
Badalona, Spain
Hospital Clinic y Provincial de Barcelona
Barcelona, Spain
Hospital Clínico y Provincial de Barcelona
Barcelona, Spain
Hospital de la Santa Creu i Sant Pau.
Barcelona, Spain
Hospital de la Santa Creu i Sant Pau.
Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital de la santa Creu i Sant Pau
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital Duran i Reynals - ICO L'Hospitalet
Barcelona, Spain
Basurtuko Ospitalea
Basurto, Spain
Complejo Hospitalario de Cáceres
Cáceres, Spain
Complejo Hospitalario Reina Sofía
Córdoba, Spain
Area Hospitalaria Juan Ramón Jimenez
Huelva, Spain
Hospital Juan Ramón Jiménez
Huelva, Spain
Hospital del SAS de Jerez de la Frontera
Jerez de la Frontera, Spain
Hospital general de Jerez de la Frontera
Jerez de la Frontera, Spain
Hospital Arnau de Vilanova
Lleida, Spain
Complexo Hospitalario Xeral-Calde
Lugo, Spain
Clínica La Concepción
Madrid, Spain
Clínica Puerta de Hierro
Madrid, Spain
Hospital 12 de Octubre. Madrid
Madrid, Spain
Hospital Clinico San Carlos
Madrid, Spain
Hospital Clínico San Carlos de Madrid
Madrid, Spain
Hospital Clínico San Carlos de Madrid
Madrid, Spain
Hospital de Fuenlabrada
Madrid, Spain
Hospital de la Princesa
Madrid, Spain
Hospital de Madrid, S.A.- Norte Hospital General
Madrid, Spain
Hospital Gregorio Marañón
Madrid, Spain
Hospital Ramón y Cajal
Madrid, Spain
Hospital Universitario de la Princesa
Madrid, Spain
Hospital Universitario Princcipe de Asturias
Madrid, Spain
Althaia, Xarxa Asistencial de Manresa
Manresa, Spain
. Hospital Clínico Universitario Virgen de la Victoria
Málaga, Spain
. Hospital Clínico Universitario Virgen de la Victoria
Málaga, Spain
Hospital Carlos Haya
Málaga, Spain
Hospital Carlos Haya
Málaga, Spain
Hospital Carlos Haya
Málaga, Spain
Hospital de Mérida
Mérida, Spain
Hospital General Univeristario Morales Messeguer
Murcia, Spain
Hospital Sta. Maria del Rosell
Murcia, Spain
Hospital del Río Carrión
Palencia, Spain
Hospital de Gran Canaria Doctor Negrín
Palma de Gran Canaria, Spain
Clínica Universitaria de Navarra
Pamplona, Spain
Hospital de Montecelo
Pontevedra, Spain
Corporació Sanitaria Parc Taulí
Sabadell, Spain
Hospital Clínico de Salamanca
Salamanca, Spain
Hospital Clínico Universitario de Salamanca
Salamanca, Spain
Hospital Clínico Universitario
Salamanca, Spain
Hospital de Donostia
San Sebastián, Spain
Hoaspital Marqués de Valdecilla
Santander, Spain
Hospital General de Segovia
Segovia, Spain
Complejo Hospitalario Regional Virgen del Rocío
Seville, Spain
Hospital Joan XIII de
Tarragona, Spain
Hospital Joan XXIII
Tarragona, Spain
Hospital Clínico de Valencia.
Valencia, Spain
Hospital Clínico Universitario de Valencia
Valencia, Spain
Hospital Clínico Universitario
Valencia, Spain
Hospital Clínic
Valencia, Spain
Hospital Dr Pesset
Valencia, Spain
Hospital La Fe
Valencia, Spain
Hospital Universitario Dr. Peset
Valencia, Spain
Hospital Clínico de Valladolid
Valladolid, Spain
Complejo Hospitalario Xeral-Cies
Vigo, Spain
Hospital do Meixoeiro
Vigo, Spain
Hospital Txagorritxu
Vitoria-Gasteiz, Spain
Hospital Clínico Lozano Blesa
Zaragoza, Spain
Related Publications (1)
Ribera JM, Garcia O, Moreno MJ, Barba P, Garcia-Cadenas I, Mercadal S, Montesinos P, Barrios M, Gonzalez-Campos J, Martinez-Carballeira D, Gil C, Ribera J, Vives S, Novo A, Cervera M, Serrano J, Lavilla E, Abella E, Tormo M, Amigo ML, Artola MT, Genesca E, Bravo P, Garcia-Belmonte D, Garcia-Guinon A, Hernandez-Rivas JM, Feliu E; PETHEMA Group of the Spanish Society of Hematology. Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group. Cancer. 2019 Aug 15;125(16):2810-2817. doi: 10.1002/cncr.32156. Epub 2019 Apr 23.
PMID: 31012967DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 12, 2011
First Posted
December 14, 2011
Study Start
January 1, 2008
Primary Completion
December 1, 2022
Study Completion
December 1, 2022
Last Updated
January 19, 2022
Record last verified: 2022-01