Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)
APL-R2007: Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)
1 other identifier
interventional
60
1 country
86
Brief Summary
Summary Acute promyelocytic leukemia is defined by a characteristic morphology (AML FAB M3/M3v), by the specific translocation t(15;17) and its molecular correlates (PML/RARa and RARa/PML). Thereby it can be separated from all other forms of acute leukemia. By all-trans retinoic acid in combination with chemotherapy cure rates of 70 to 80% can be reached. On average, about 10% of patients still die in the early phase of the treatment and about 20 to 30% relapse. Molecular monitoring of the minimal residual disease (MRD) by qualitative nested RT-PCR and quantitative REAL-time PCR of PML/RARa allows to follow the individual kinetics of MRD and to identify patients with an imminent hematological relapse. A standardized treatment for patients with relapsed APL has not yet been established. With arsenic trioxide (ATO) monotherapy remission rates over 80% were achieved and long-lasting molecular remissions are described. The drug was mostly well tolerated. ATO exerts a dose dependent dual effect on APL blasts, apoptosis in higher and partial differentiation in lower concentrations. ATO was also successfully administered before allogeneic and autologous transplantation. ATO is approved for the treatment of relapsed and refractory APL in Europe and in the USA. After remission induction, there are several options for postremission therapy Previous studies shows that risk of relapse is higher in patients treated with ATO postremission in monotherapy , than in other that receive ATO plus chemotherapy or transplantation (TPH). Also, compared with chemotherapy, ATO induction and consolidation has a favorable impact in posterior response to transplantation. It is due to a low toxicity or a best quality of remission to TPH. It seems better, for these reasons, the intensification with TPH (autologous or allogenic) in patients with relapsed APL treated with ATO. For another hand, patients no candidates to TPH can be treated with ATO combined with other active agents in APL, as ATRA, anthracyclines o Mylotarg
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 Jul 2007
Longer than P75 for phase_4
86 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2007
CompletedFirst Submitted
Initial submission to the registry
July 19, 2007
CompletedFirst Posted
Study publicly available on registry
July 20, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2014
CompletedOctober 28, 2014
October 1, 2014
7.3 years
July 19, 2007
October 27, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Evaluate the hematological and molecular remission rate after induction and consolidation with ATO
1 year
Evaluate the induction mortality with ATO in monotherapy
1 year
Evaluate the hematological and molecular relapse rate in patients treated with autologous transplantation, allogenic transplantation or ATO + ATRA +/- Mylotarg
1 year
Secondary Outcomes (4)
Evaluate kinetics of the MDR of PML/RARa during and after ATO
2 years
Evaluate the mortality related with postremission treatment
1 year
Side effects of ATO and the different treatments post-consolidation
2 years
Overall survival
2 years
Interventions
Induction ATO 0.15 mg/kg/day IV until CR or a maximum of 60 days In isolated molecular relapse ATO will be administered at same dose, 5 days a week, during 6 weeks. Consolidation ATO 0.15 mg/kg/day IV 5 days week, during 5 weeks
Autologous Transplantation
Allogenic Transplantation
Consolidation: ATRA 45 mg/m²/day oral during 5 weeks
Eligibility Criteria
You may qualify if:
- ECOG ≤ 3.
- Patients in first or subsequent hematological or molecular relapse of APL
- Persistence of a positive PCR (positive PCR after 3 consolidation cycles of first line therapy).
- Diagnostic measures Confirmation of relapse by RT-PCR of PML/RARa, cytogenetics, FISH or positive PGM3.
- Age over 18 years (No upper age limit)
- Informed consent of the patient
You may not qualify if:
- ECOG 4.
- Heart failure NYHA grade III and IV.
- Renal or hepatic failure WHO grade ³III
- Positive HIV.
- Psychological dysfunction
- Associated active neoplasia
- Pregnancy.
- Arsenic Hypersensibility.
- QTc-interval prolonged over 460 msec before therapy (normal electrolytes, no other drugs prolonging the QT-interval )
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (86)
Hospital General de Alicante
Alicante, Alicante, Spain
Hospital Ntra. Sra. Sonsoles
Ávila, Avila, Spain
Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, Spain
Hospital del Mar
Barcelona, Barcelona, Spain
Hospital Valle Hebrón
Barcelona, Barcelona, Spain
Hospital de Mataró
Mataró, Barcelona, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, Spain
Hospital general de Castellón
Castelló, Castellón, Spain
Hospital Puerta del Mar
Cadiz, Cádiz, Spain
Complejo Hospitalario Reina Sofía
Córdoba, Córdoba, Spain
Hospital Virgen de las Nieves
Granada, Granada, Spain
Hospital Médico Quirúrgico Ciudad de Jaén
Jaén, Jaen, Spain
Hospital Juan Canalejo
A Coruña, La Coruña, Spain
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, La Coruña, Spain
Hospital Arnau de Vilanova
Lleida, Lleida, Spain
Hospital de Alcorcón
Alcorcón, Madrid, Spain
Clínica La Concepción
Madrid, Madrid, Spain
Clínica Puerta de Hierro
Madrid, Madrid, Spain
Hospital Clínico San Carlos de Madrid
Madrid, Madrid, Spain
Hospital General Universitario Gregorio Marañón, Madrid
Madrid, Madrid, Spain
. Hospital Clínico Universitario Virgen de la Victoria
Málaga, Málaga, Spain
Clínica Universitaria de Navarra
Pamplona, Navarre, Spain
Hospital del Río Carrión
Palencia, Palencia, Spain
Hospital Son Dureta
Palma de Mallorca, Palma de Mallorca, Spain
Hospital Son Llàtzer
Palma de Mallorca, Palma de Mallorca, Spain
Hospital Central de Asturias
Oviedo, Principality of Asturias, Spain
Hospital Joan XXIII
Tarragona, Tarragona, Spain
Hospital Verge de la Cinta
Tortosa, Tarragona, Spain
Hospital Clínic
Valencia, Valencia, Spain
Hospital General Universitario
Valencia, Valencia, Spain
Hospital La Fe
Valencia, Valencia, Spain
Complejo Hospitalario Xeral-Cies
Vigo, Vigo, Spain
Hospital Clínico Lozano Blesa
Zaragoza, Zaragoza, Spain
Complejo Hospitalario Universitario de Albacete
Albacete, Spain
Fundación Hospital Alcorcón
Alcorcón, Spain
Hospital de la Ribera
Alzira, Spain
Hospital Clinic
Barcelona, Spain
Basurtuko Ospitalea
Basurto, Spain
Hospital de Cruces
Bilbao, Spain
Complejo Hospitalario de Cáceres
Cáceres, Spain
Hospital Donostia
Donostia / San Sebastian, Spain
Hospital General de Elda
Elda, Spain
Hospital de Fuenlabrada
Fuenlabrada, Spain
Hospital General de Guadalajara
Guadalajara, Spain
Area Hospitalaria Juan Ramón Jimenez
Huelva, Spain
Hospital de San Jorge
Huesca, Spain
Hospital de Jerez de la Frontera
Jerez de la Frontera, Spain
Hospital General de Lanzarote
Lanzarote, Spain
Complejo Hospitalario León
León, Spain
Complexo Hospitalario Xeral-Calde
Lugo, Spain
Clínica Moncloa
Madrid, Spain
Clínica Puerta de Hierro
Madrid, Spain
Clínica Rúber
Madrid, Spain
Fundación Jiménez Díaz
Madrid, Spain
Hospital 12 de Octubre
Madrid, Spain
Hospital Central de la Defensa
Madrid, Spain
Hospital de la Princesa
Madrid, Spain
Hospital Doce de Octubre
Madrid, Spain
Hospital la Paz
Madrid, Spain
Althaia, Xarxa Asistencial de Manresa
Manresa, Spain
Fundación Hospital Sant Joan de Déu de Martorell
Martorell, Spain
Hospital de Mérida
Mérida, Spain
Hospital de Móstoles
Móstoles, Spain
Hospital General Morales Meseguer
Murcia, Spain
Hospital de Gran Canaria Doctor Negrín
Palma de Gran Canaria, Spain
Hospital Verge del Toro
Palma de Mallorca, Spain
Complejo Hospitalario de Pontevedra_Hospital Montecelo
Pontevedra, Spain
Complejo Hospitalario de Pontevedra_Hospital Provincial
Pontevedra, Spain
Corporació Sanitaria Parc Taulí
Sabadell, Spain
Hospital de Sagunto
Sagunto, Spain
Hospital Clínico de Salamanca
Salamanca, Spain
Clínica Sant Camil
Sant Pere de Ribes, Spain
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Spain
Hospital General de Segovia
Segovia, Spain
H.U. Virgen del Rocio
Seville, Spain
Hospital Nuestra Señora del Prado
Toledo, Spain
Fundación Instituto Valenciano de Oncología
Valencia, Spain
Hospital Dr. Peset
Valencia, Spain
Hospital Francesc de Borja
Valencia, Spain
Hospital Clínico de Valladolid
Valladolid, Spain
Hospital Comarcal Pius de Valls
Valls, Spain
Comarcal de Vinaros
Vinaròs, Spain
Hospital Txagorritxu
Vitoria-Gasteiz, Spain
Hospital de Galdakao
Vizcaya, Spain
Hospital Miguel Servet
Zaragoza, Spain
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Sanz Miguel Angel, Dr
Hospital La Fe
- STUDY CHAIR
Esteve Jordi, Dr
Hospital Clinic of Barcelona
- STUDY CHAIR
Montesinos Pau, Dr
Hospital General Universitario de Valencia
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 19, 2007
First Posted
July 20, 2007
Study Start
July 1, 2007
Primary Completion
October 1, 2014
Study Completion
October 1, 2014
Last Updated
October 28, 2014
Record last verified: 2014-10