Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by PETHEMA Foundation
Sponsor:
Information provided by (Responsible Party):
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00504764
First received: July 19, 2007
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

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


Condition Intervention Phase
Acute Promyelocytic Leukemia
Drug: Arsenic Trioxide
Procedure: Autologous Transplantation
Procedure: Allogenic Transplantation
Drug: ATRA
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: APL-R2007: Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • Evaluate the hematological and molecular remission rate after induction and consolidation with ATO [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Evaluate the induction mortality with ATO in monotherapy [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Evaluate the hematological and molecular relapse rate in patients treated with autologous transplantation, allogenic transplantation or ATO + ATRA +/- Mylotarg [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate kinetics of the MDR of PML/RARa during and after ATO [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Evaluate the mortality related with postremission treatment [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Side effects of ATO and the different treatments post-consolidation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: July 2007
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Arsenic Trioxide

    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

    Procedure: Autologous Transplantation
    Autologous Transplantation
    Procedure: Allogenic Transplantation
    Allogenic Transplantation
    Drug: ATRA
    Consolidation: ATRA 45 mg/m²/day oral during 5 weeks
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 )
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00504764

Contacts
Contact: Sanz Miguel Angel, Dr 34 (96) 197 3057 msanz@uv.es
Contact: Priego Miguel, Data manager 34 635 964 539 miguepriego@gmail.com

  Hide Study Locations
Locations
Spain
Hospital Central de Asturias Recruiting
Oviedo, Asturias, Spain
Contact: Carrera Dolores, Dr         
Principal Investigator: Carrera Dolores, Dr         
Hospital Germans Trias i Pujol Recruiting
Badalona, Barcelona, Spain
Contact: Jospe Mª Ribera, Doctor         
Principal Investigator: Ribera Josep Mª, Dr         
Hospital de Mataró Recruiting
Mataró, Barcelona, Spain
Contact: Bosch LLobet, Dr         
Principal Investigator: Bosch Alba, Dr         
Hospital general de Castellón Recruiting
Castello, Castellón, Spain
Contact: García Raimundo, Dr         
Principal Investigator: Garcia Raimundo, Dr         
Complejo Hospitalario Universitario de Santiago Recruiting
Santiago de Compostela, La Coruña, Spain
Contact: Bello José Luis, Dr         
Principal Investigator: Bello José Luis, Dr         
Hospital de Alcorcón Recruiting
Alcorcón, Madrid, Spain
Contact: Villalón lucía, Dr         
Principal Investigator: Villalón Lucía, Dr         
Clínica Universitaria de Navarra Recruiting
Pamplona, Navarra, Spain
Contact: Prosper Felipe, Dr         
Principal Investigator: Prosper Felipe, Dr         
Hospital Verge de la Cinta Recruiting
Tortosa, Tarragona, Spain
Contact: Font llorenç, Dr         
Principal Investigator: Font Llorenç, Dr         
Complejo Hospitalario Universitario de Albacete Recruiting
Albacete, Spain
Principal Investigator: Santiago José, Dr         
Fundación Hospital Alcorcón Recruiting
Alcorcón, Spain
Principal Investigator: Peñalver Francisco Javier, Dr         
Hospital General de Alicante Recruiting
Alicante, Spain
Principal Investigator: Rivas Concepción, Dr         
Hospital de la Ribera Recruiting
Alzira, Spain
Hospital Ntra. Sra. Sonsoles Recruiting
Avila, Spain
Contact: Barez Abelardo, Dr         
Principal Investigator: Barez Abelardo, Dr         
Hospital del Mar Recruiting
Barcelona, Spain
Contact: Besses Carles, Dr         
Principal Investigator: Besses Carles, Dr         
Hospital Valle Hebrón Recruiting
Barcelona, Spain
Principal Investigator: Bueno Javier, Dr         
Hospital Clinic Recruiting
Barcelona, Spain
Principal Investigator: Esteve Jordi, Dr         
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain
Contact: Sureda Anna, Dr         
Principal Investigator: Sureda Anna, Dr         
Basurtuko Ospitalea Recruiting
Basurto, Spain
Contact: Beltran de Heredia José Mª, Dr         
Principal Investigator: Beltran de Heredia Jose Mª, Dr         
Hospital de Cruces Recruiting
Bilbao, Spain
Principal Investigator: García Juan Carlos, Dr         
Complejo Hospitalario de Cáceres Recruiting
Cáceres, Spain
Contact: Bergua Juan Miguel, Dr         
Principal Investigator: Bergua Juan Miguel, Dr         
Hospital Puerta del Mar Recruiting
Cádiz, Spain
Contact: Capote Francisco Javier, Dr         
Principal Investigator: Capote Francisco Javier, Dr         
Complejo Hospitalario Reina Sofía Recruiting
Córdoba, Spain
Contact: Torres Antonio, Dr         
Principal Investigator: Torres Antonio, DR         
Hospital Donostia Recruiting
Donostia, Spain
Principal Investigator: Bengoetxea Enrique, Dr         
Hospital General de Elda Recruiting
Elda, Spain
Principal Investigator: Borrego Domingo, Dr         
Hospital de Fuenlabrada Recruiting
Fuenlabrada, Spain
Principal Investigator: Hernández José Angel, DR         
Hospital Virgen de las Nieves Recruiting
Granada, Spain
Contact: Jurado Manuel, Dr         
Principal Investigator: Jurado Manuel, Dr         
Hospital General de Guadalajara Recruiting
Guadalajara, Spain
Principal Investigator: Diaz Miguel, Dr         
Area Hospitalaria Juan Ramón Jimenez Recruiting
Huelva, Spain
Contact: Fernández Antonio, Dr         
Principal Investigator: Fernández Antonio, Dr         
Hospital de San Jorge Recruiting
Huesca, Spain
Principal Investigator: Puente Fernando         
Hospital Médico Quirúrgico Ciudad de Jaén Recruiting
Jaen, Spain
Contact: Alcala Antonio, Dr         
Principal Investigator: Alcalá Antonio, Dr         
Hospital de Jerez de la Frontera Recruiting
Jerez de la Frontera, Spain
Principal Investigator: León Angel, Dr         
Hospital Juan Canalejo Recruiting
La Coruña, Spain
Contact: Deben Guillermo, Dr         
Principal Investigator: Deben Guillermo, Dr         
Hospital General de Lanzarote Recruiting
Lanzarote, Spain
Principal Investigator: Calvo José Manuel, Dr         
Complejo Hospitalario León Recruiting
Leon, Spain
Principal Investigator: Ramos Fernando, Dr         
Hospital Arnau de Vilanova Recruiting
Lleida, Spain
Contact: Sanchez Juan Manuel, Dr         
Principal Investigator: Sanchez Juan Manuel, Dr         
Complexo Hospitalario Xeral-Calde Recruiting
Lugo, Spain
Principal Investigator: Arias Jesús, Dr         
Hospital Clínico San Carlos de Madrid Recruiting
Madrid, Spain
Contact: Diaz Mediavilla Joaquin, Dr         
Principal Investigator: Díaz Mediavilla Joaquín, Dr         
Hospital Doce de Octubre Recruiting
Madrid, Spain
Principal Investigator: Lahuerta Juan José, Dr         
Hospital Central de la Defensa Recruiting
Madrid, Spain
Principal Investigator: Montero Antonio, Dr         
Clínica Moncloa Recruiting
Madrid, Spain
Principal Investigator: Perez Angeles, Dr         
Hospital General Universitario Gregorio Marañón, Madrid Recruiting
Madrid, Spain
Contact: Serrano David, Dr         
Principal Investigator: Serrano David, Dr         
Clínica Puerta de Hierro Recruiting
Madrid, Spain
Principal Investigator: Krisnk Isabel, Dr         
Hospital de la Princesa Recruiting
Madrid, Spain
Contact: Adrián Alegre, Dr         
Clínica Puerta de Hierro Recruiting
Madrid, Spain
Contact: Nicolás Manuel, Dr         
Principal Investigator: Nicolás Manuel, Dr         
Clínica La Concepción Recruiting
Madrid, Spain
Contact: Román Alejandro, Dr         
Principal Investigator: Román Alejandro, Dr         
Fundación Jiménez Díaz Recruiting
Madrid, Spain
Principal Investigator: Prieto Elena, Dr         
Hospital 12 de Octubre Recruiting
Madrid, Spain
Principal Investigator: de la Serna Javier, Dr         
Clínica Rúber Recruiting
Madrid, Spain
Principal Investigator: Martínez Carmen, Dr         
Hospital la Paz Recruiting
Madrid, Spain
Contact: De Paz Raquel, Dr         
Althaia, Xarxa Asistencial de Manresa Recruiting
Manresa, Spain
Principal Investigator: Subira Maricel, Dr         
Fundación Hospital Sant Joan de Déu de Martorell Recruiting
Martorell, Spain
Principal Investigator: Las Heras German, Dr         
Hospital General Morales Meseguer Recruiting
Murcia, Spain
Principal Investigator: De Arriba Felipe, Dr         
. Hospital Clínico Universitario Virgen de la Victoria Recruiting
Málaga, Spain
Principal Investigator: Moreno Mª José, Dr         
Hospital de Mérida Recruiting
Mérida, Spain
Principal Investigator: Lopez Carlos, Dr         
Hospital de Móstoles Recruiting
Móstoles, Spain
Principal Investigator: Jaro Esther, Dr         
Hospital del Río Carrión Recruiting
Palencia, Spain
Contact: Ortega Frenando, Dr         
Principal Investigator: Ortega Fernando, Dr         
Hospital de Gran Canaria Doctor Negrín Recruiting
Palma de Gran Canaria, Spain
Principal Investigator: Suarez Alexia, Dr         
Hospital Verge del Toro Recruiting
Palma de Mallorca, Spain
Principal Investigator: Galán Pilar, Dr         
Hospital Son Dureta Recruiting
Palma de Mallorca, Spain
Contact: Besalduch Joan, Dr         
Principal Investigator: Besalduch Joan, Dr         
Hospital Son Llàtzer Recruiting
Palma de Mallorca, Spain
Contact: Joan Bargay, Dr         
Contact: Catalina Forteza, Dr         
Principal Investigator: Joan Bargay, Dr         
Complejo Hospitalario de Pontevedra_Hospital Montecelo Recruiting
Pontevedra, Spain
Principal Investigator: Allegue Mª José, Dr         
Complejo Hospitalario de Pontevedra_Hospital Provincial Recruiting
Pontevedra, Spain
Principal Investigator: Constela Manuel, Dr         
Corporació Sanitaria Parc Taulí Recruiting
Sabadell, Spain
Principal Investigator: Rámila Elena, Dr         
Hospital de Sagunto Recruiting
Sagunto, Spain
Principal Investigator: Navarro Isabel, Dr         
Hospital Clínico de Salamanca Recruiting
Salamanca, Spain
Contact: Jesús San Miguel, Dr         
Clínica Sant Camil Recruiting
Sant Pere de Ribes, Spain
Principal Investigator: Asensio Antonio, Dr         
Hospital Universitario Marqués de Valdecilla Recruiting
Santander, Spain
Contact: Conde Eulogio, Dr         
Principal Investigator: Conde Eulogio, Dr         
Hospital General de Segovia Recruiting
Segovia, Spain
Principal Investigator: Hernández José Mariano         
H.U. Virgen del Rocio Recruiting
Sevilla, Spain
Principal Investigator: Parody Ricardo, Dr         
Hospital Joan XXIII Recruiting
Tarragona, Spain
Contact: Escoda Lourdes, Dr         
Principal Investigator: Escoda Lourdes         
Hospital Universitario de Canarias Recruiting
Tenerife, Spain
Contact: Miguel Teodoro Hernández, Dr         
Hospital Nuestra Señora del Prado Recruiting
Toledo, Spain
Principal Investigator: Solano Fernando, DR         
Hospital Dr. Peset Recruiting
Valencia, Spain
Principal Investigator: Sayas Mª José         
Hospital General Universitario Recruiting
Valencia, Spain
Contact: Montesinos Pau, Dr         
Principal Investigator: Sanchez Magdalena, Dr         
Hospital Clínic Recruiting
Valencia, Spain
Contact: Terol Maria José, Dr         
Principal Investigator: Terol Mª José, Dr         
Hospital Francesc de Borja Recruiting
Valencia, Spain
Principal Investigator: Ruiz Mª Angeles, Dr         
Hospital La Fe Recruiting
Valencia, Spain
Contact: Sanz Miguel Angel         
Principal Investigator: Sanz Miguel Angel, Dr         
Fundación Instituto Valenciano de Oncología Recruiting
Valencia, Spain
Principal Investigator: Llorente Pablo, Dr         
Hospital Clínico de Valladolid Recruiting
Valladolid, Spain
Principal Investigator: Fernandez Calvo Francisco, Dr         
Hospital Comarcal Pius de Valls Recruiting
Valls, Spain
Principal Investigator: Herranz Mª José, Dr         
Complejo Hospitalario Xeral-Cies Recruiting
Vigo, Spain
Contact: Poderós Concepción, Dr         
Principal Investigator: Poderós Concepción, Dr         
Comarcal de Vinaros Recruiting
Vinaros, Spain
Principal Investigator: Montagud Mario, Dr         
Hospital Txagorritxu Recruiting
Vitoria, Spain
Contact: Guinea Josep Mª, Dr         
Principal Investigator: Guinea José Mª, Dr         
Hospital de Galdakao Recruiting
Vizcaya, Spain
Principal Investigator: Ojanguren Jesús, Dr         
Hospital Clínico Lozano Blesa Recruiting
Zaragoza, Spain
Contact: Palomera Luis, Dr         
Principal Investigator: Palomera Luis, Dr         
Hospital Miguel Servet Recruiting
Zaragoza, Spain
Principal Investigator: Rubio Araceli, Dr         
Sponsors and Collaborators
PETHEMA Foundation
Investigators
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 de Valencia
  More Information

Additional Information:
No publications provided

Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT00504764     History of Changes
Other Study ID Numbers: LAP-R2007
Study First Received: July 19, 2007
Last Updated: November 19, 2013
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
Relapsed Acute Promyelocytic Leukemia
Arsenic Trioxide

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Arsenic trioxide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014