Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00504764
First received: July 19, 2007
Last updated: October 27, 2014
Last verified: October 2014
  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
Study Completion Date: October 2014
Primary Completion Date: October 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

  Hide Study Locations
Locations
Spain
Hospital Central de Asturias
Oviedo, Asturias, Spain
Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital de Mataró
Mataró, Barcelona, Spain
Hospital general de Castellón
Castello, Castellón, Spain
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, La Coruña, Spain
Hospital de Alcorcón
Alcorcón, Madrid, Spain
Clínica Universitaria de Navarra
Pamplona, Navarra, Spain
Hospital Verge de la Cinta
Tortosa, Tarragona, Spain
Complejo Hospitalario Universitario de Albacete
Albacete, Spain
Fundación Hospital Alcorcón
Alcorcón, Spain
Hospital General de Alicante
Alicante, Spain
Hospital de la Ribera
Alzira, Spain
Hospital Ntra. Sra. Sonsoles
Avila, Spain
Hospital Valle Hebrón
Barcelona, Spain
Hospital Clinic
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Basurtuko Ospitalea
Basurto, Spain
Hospital de Cruces
Bilbao, Spain
Complejo Hospitalario de Cáceres
Cáceres, Spain
Hospital Puerta del Mar
Cádiz, Spain
Complejo Hospitalario Reina Sofía
Córdoba, Spain
Hospital Donostia
Donostia, Spain
Hospital General de Elda
Elda, Spain
Hospital de Fuenlabrada
Fuenlabrada, Spain
Hospital Virgen de las Nieves
Granada, Spain
Hospital General de Guadalajara
Guadalajara, Spain
Area Hospitalaria Juan Ramón Jimenez
Huelva, Spain
Hospital de San Jorge
Huesca, Spain
Hospital Médico Quirúrgico Ciudad de Jaén
Jaen, Spain
Hospital de Jerez de la Frontera
Jerez de la Frontera, Spain
Hospital Juan Canalejo
La Coruña, Spain
Hospital General de Lanzarote
Lanzarote, Spain
Complejo Hospitalario León
Leon, Spain
Hospital Arnau de Vilanova
Lleida, Spain
Complexo Hospitalario Xeral-Calde
Lugo, Spain
Fundación Jiménez Díaz
Madrid, Spain
Hospital la Paz
Madrid, Spain
Hospital Central de la Defensa
Madrid, Spain
Hospital 12 de Octubre
Madrid, Spain
Clínica Rúber
Madrid, Spain
Hospital Clínico San Carlos de Madrid
Madrid, Spain
Clínica La Concepción
Madrid, Spain
Hospital de la Princesa
Madrid, Spain
Clínica Moncloa
Madrid, Spain
Hospital General Universitario Gregorio Marañón, Madrid
Madrid, Spain
Clínica Puerta de Hierro
Madrid, Spain
Hospital Doce de Octubre
Madrid, Spain
Althaia, Xarxa Asistencial de Manresa
Manresa, Spain
Fundación Hospital Sant Joan de Déu de Martorell
Martorell, Spain
Hospital General Morales Meseguer
Murcia, Spain
. Hospital Clínico Universitario Virgen de la Victoria
Málaga, Spain
Hospital de Mérida
Mérida, Spain
Hospital de Móstoles
Móstoles, Spain
Hospital del Río Carrión
Palencia, Spain
Hospital de Gran Canaria Doctor Negrín
Palma de Gran Canaria, Spain
Hospital Son Llàtzer
Palma de Mallorca, Spain
Hospital Verge del Toro
Palma de Mallorca, Spain
Hospital Son Dureta
Palma de Mallorca, Spain
Complejo Hospitalario de Pontevedra_Hospital Provincial
Pontevedra, Spain
Complejo Hospitalario de Pontevedra_Hospital Montecelo
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 Marqués de Valdecilla
Santander, Spain
Hospital General de Segovia
Segovia, Spain
H.U. Virgen del Rocio
Sevilla, Spain
Hospital Joan XXIII
Tarragona, Spain
Hospital Universitario de Canarias
Tenerife, Spain
Hospital Nuestra Señora del Prado
Toledo, Spain
Hospital Dr. Peset
Valencia, Spain
Hospital Francesc de Borja
Valencia, Spain
Hospital Clínic
Valencia, Spain
Hospital General Universitario
Valencia, Spain
Fundación Instituto Valenciano de Oncología
Valencia, Spain
Hospital La Fe
Valencia, Spain
Hospital Clínico de Valladolid
Valladolid, Spain
Hospital Comarcal Pius de Valls
Valls, Spain
Complejo Hospitalario Xeral-Cies
Vigo, Spain
Comarcal de Vinaros
Vinaros, Spain
Hospital Txagorritxu
Vitoria, Spain
Hospital de Galdakao
Vizcaya, Spain
Hospital Miguel Servet
Zaragoza, Spain
Hospital Clínico Lozano Blesa
Zaragoza, Spain
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: October 27, 2014
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
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Arsenic trioxide
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014