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Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase IV Treatment Active 18 and over Other LAP-R2007 NCT00504764

Trial Description

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

Further Study Information

Induction ATO 0.15 mg/kg/día IV in continuous perfusion 1-2 hours/day until complete response (CR) or maximum of 60 days.

Oral hydroxyurea treatment (initial dose 2 g/day)is recommended in patients with leucocyte counts at relapse >10x109/L or in the two first weeks of induction.

Isolated molecular relapsed patients will be treated with ATO (same dose) 5 days at week, during 6 weeks.

Consolidation ATO 0.15 mg/kg/día IV 5 days at week, during 5 weeks, combined with oral ATRA 45 mg/m²/day during the same 5 weeks.

Post-consolidation therapy TPH (autologous or allogenic) in candidate patients. In case of molecular remission, is recommended autologous-TPH.

Patients no candidates to auto-TPH or alo-TPH, should will follow treatment with ATO cycles + ATRA +/- Mylotarg.

1. Option Alo-TPH If PCR post-consolidation is negative is recommended auto-TPH. However, if alo-TPH is decided, it will be done immediately without preceding chemotherapy.

If PCR post-consolidation is positive, should done alo-TPH.

2. Option Auto-TPH If PCR post-consolidation is negative it will be administered one cycle of MTZ + Ara-C follow by auto-TPH.

In cas of failure: a) if patient has autologous stem cells preserved (PCR negative) are suitable for auto-TPH; b) patients with HLA-compatible donor who are suitable for allogenic stem cell transplantation should be transplanted; c) Patients who are not eligible for allogenic or autologous transplantation, receive various cycles with ATO + ATRA combined or not with Mylotarg.

If PCR post-consolidation is positive and patient is eligible for allogenic TPH, should be done a allogenic TPH.

If patient is no eligible for allogenic TPH or dont has compatible donor, will be administrate one cycle of MTZ + Ara-C and collect stem cells. Autologous transplantation will be done if after this cycle, a molecular remission is obtained. No molecular remission or no enough stem cells collection, patient follows treatment with subsequent cycles of ATO + ATRA combined or no with Mylotarg.

3. ATO + ATRA combined or no with Mylotarg Patients no eligible to autologous TPH or allogenic TPH follows treatment with subsequent cycles of ATO + ATRA combined or no with Mylotarg.

If Mylotarg is no possible, treatment will be with subsequent cycles of ATO + ATRA.

ATO + ATRA + Mylotarg: Mylotarg 6 mg/m2 day 1, ATO 0.15 mg/kg days 1 to 5 and 8 to 12, and ATRA 45 mg/m2/d days 1 to 15. Doses of mylotarg should be reduced to 3 mg/m2 in patients aged over 60 years. Administration of 3 cycles with a month interval, follow of 3 to 6 cycles of ATO + ATRA without Mylotarg. After, ATRA 45 mg/m2/d 15 days every 3 months until complete two years of maintenance.

ATO + ATRA: ATO 0.15 mg/kg days 1 to 5 and 8 to 12, and ATRA 45 mg/m2/d days 1 to 15, every 29 days. Administration of 9 cycles, and followed by ATRA 45 mg/m2/d during 15 days every 3 months until complete two years of maintenance.

Eligibility 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 )

Trial Contact Information

Trial Lead Organizations/Sponsors

Program for the Study and Treatment of Hematological Malignancies

Sanz Miguel Angel, Dr

Study Chair

Esteve Jordi, Dr

Study Chair

Montesinos Pau, Dr

Study Chair

Sanz Miguel Angel, Dr		Ph: 34 (96) 197 3057
		Email: msanz@uv.es

Priego Miguel, Data manager		Ph: 34 635 964 539
		Email: miguepriego@gmail.com

Spain
	Albacete
	Hospital General de Albacete
		Santiago José, Dr	Principal Investigator
	Alcorcón
	Fundacion Hospital Alcorcon
		Peñalver Francisco Javier, Dr	Principal Investigator
		Villalón lucía, Dr
		Villalón Lucía, Dr	Principal Investigator
	Alicante
	Hospital General - Alicante
		Rivas Concepción, Dr	Principal Investigator
	Alzira
	Hospital de La Ribera
	Avila
	Hospital Nuestra Senora de Sonsoles
		Barez Abelardo, Dr
		Barez Abelardo, Dr	Principal Investigator
	Badalona
	Hospital Universitari Germans Trias i Pujol
		Jospe Mª Ribera, Doctor
		Ribera Josep Mª, Dr	Principal Investigator
	Barcelona
	Hospital Clinic de Barcelona
		Esteve Jordi, Dr	Principal Investigator
	Hospital de la Santa Cruz i Sant Pau
		Sureda Anna, Dr
		Sureda Anna, Dr	Principal Investigator
	Hospital Del Mar
		Besses Carles, Dr
		Besses Carles, Dr	Principal Investigator
	Vall d'Hebron University Hospital
		Bueno Javier, Dr	Principal Investigator
	Basurto
	Hospital de Basurto
		Beltran de Heredia José Mª, Dr
		Beltran de Heredia Jose Mª, Dr	Principal Investigator
	Bilbao
	Hospital de Cruces
		García Juan Carlos, Dr	Principal Investigator
	Cáceres
	Complejo Hospitalario de Caceres
		Bergua Juan Miguel, Dr
		Bergua Juan Miguel, Dr	Principal Investigator
	Cádiz
	Hospital Universitario Puerta Del Mar
		Capote Francisco Javier, Dr
		Capote Francisco Javier, Dr	Principal Investigator
	Castello
	Hospital General de Castellon
		García Raimundo, Dr
		Garcia Raimundo, Dr	Principal Investigator
	Córdoba
	Hospital Universarito Reina Sofia
		Torres Antonio, Dr
		Torres Antonio, DR	Principal Investigator
	Donostia
	Hospital Donostia
		Bengoetxea Enrique, Dr	Principal Investigator
	Elda
	Hospital General de Elda
		Borrego Domingo, Dr	Principal Investigator
	Fuenlabrada
	Hospital Universitario de Fuenlabrada
		Hernández José Angel, DR	Principal Investigator
	Granada
	Hospital Virgen de las Nieves
		Jurado Manuel, Dr
		Jurado Manuel, Dr	Principal Investigator
	Guadalajara
	Hospital General Universitario De Guadalajara
		Diaz Miguel, Dr	Principal Investigator
	Huelva
	Hospital Juan Ramon Jimenez
		Fernández Antonio, Dr
		Fernández Antonio, Dr	Principal Investigator
	Huesca
	Hospital San Jorge
		Puente Fernando	Principal Investigator
	Jaen
	Hospital Cuidad de Jaen
		Alcala Antonio, Dr
		Alcalá Antonio, Dr	Principal Investigator
	Jerez de la Frontera
	Hospital General de Jerez de la Frontera
		León Angel, Dr	Principal Investigator
	La Coruña
	Hospital Universitario Juan Canalejo
		Deben Guillermo, Dr
		Deben Guillermo, Dr	Principal Investigator
	Lanzarote
	Hospital General de Lanzarote
		Calvo José Manuel, Dr	Principal Investigator
	Leon
	Complejo Hospitalario de Leon
		Ramos Fernando, Dr	Principal Investigator
	Lleida
	Hospital Universitari Arnau de Vilanova
		Sanchez Juan Manuel, Dr
		Sanchez Juan Manuel, Dr	Principal Investigator
	Lugo
	Hospital Xeral de Lugo
		Arias Jesús, Dr	Principal Investigator
	Madrid
	Clinica Moncloa
		Perez Angeles, Dr	Principal Investigator
	Clinica Puerta de Hierro
		Krisnk Isabel, Dr	Principal Investigator
		Nicolás Manuel, Dr
		Nicolás Manuel, Dr	Principal Investigator
	Fundacion Jimenez Diaz
		Prieto Elena, Dr	Principal Investigator
		Román Alejandro, Dr
		Román Alejandro, Dr	Principal Investigator
	Hospital Central de la Defensa
		Montero Antonio, Dr	Principal Investigator
	Hospital de la Princesa
		Adrián Alegre, Dr
	Hospital General Universitario Gregorio Maranon
		Serrano David, Dr
		Serrano David, Dr	Principal Investigator
	Hospital Ruber Internacional
		Martínez Carmen, Dr	Principal Investigator
	Hospital Universitario 12 de Octubre
		de la Serna Javier, Dr	Principal Investigator
		Lahuerta Juan José, Dr	Principal Investigator
	Hospital Universitario La Paz
		De Paz Raquel, Dr
	Hospital Universitario San Carlos
		Diaz Mediavilla Joaquin, Dr
		Díaz Mediavilla Joaquín, Dr	Principal Investigator
	Málaga
	Hospital Universitario Virgen de la Victoria
		Moreno Mª José, Dr	Principal Investigator
	Manresa
	Althaia Xarxa Asistencial de Manresa
		Subira Maricel, Dr	Principal Investigator
	Martorell
	Fundacio Hospital Sant Joan de Deu
		Las Heras German, Dr	Principal Investigator
	Mataró
	Hospital de Mataro
		Bosch LLobet, Dr
		Bosch Alba, Dr	Principal Investigator
	Mérida
	Hospital de Merida
		Lopez Carlos, Dr	Principal Investigator
	Móstoles
	Hospital de Mostoles
		Jaro Esther, Dr	Principal Investigator
	Murcia
	Hospital General Universitario Morales Meseguer
		De Arriba Felipe, Dr	Principal Investigator
	Oviedo
	Hospital Universitario Central de Asturias
		Carrera Dolores, Dr
		Carrera Dolores, Dr	Principal Investigator
	Palencia
	Hospital del Rio Carrion
		Ortega Frenando, Dr
		Ortega Fernando, Dr	Principal Investigator
	Palma de Gran Canaria
	Hospital de Gran Canaria Dr. Negrin
		Suarez Alexia, Dr	Principal Investigator
	Palma de Mallorca
	Hospital Son Dureta
		Besalduch Joan, Dr
		Besalduch Joan, Dr	Principal Investigator
	Hospital Son Llatzer
		Joan Bargay, Dr
		Catalina Forteza, Dr
		Joan Bargay, Dr	Principal Investigator
	Hospital Verge del Toro
		Galán Pilar, Dr	Principal Investigator
	Pamplona
	Clinica Universitaria
		Prosper Felipe, Dr
		Prosper Felipe, Dr	Principal Investigator
	Pontevedra
	Complejo Hospitalario de Pontevedra
		Allegue Mª José, Dr	Principal Investigator
		Constela Manuel, Dr	Principal Investigator
	Sabadell
	Hospital de Sabadell
		Rámila Elena, Dr	Principal Investigator
	Sagunto
	Hospital de Sagunto
		Navarro Isabel, Dr	Principal Investigator
	Salamanca
	University Hospital - Salamanca
		Jesús San Miguel, Dr
	Sant Pere de Ribes
	Hospital - Residencia Sant Camil
		Asensio Antonio, Dr	Principal Investigator
	Santander
	Hospital Universitario Marques de Valdecilla
		Conde Eulogio, Dr
		E. Conde	Principal Investigator
	Santiago de Compostela
	Santiago de Compostela University Hospital
		Bello José Luis, Dr
		Bello José Luis, Dr	Principal Investigator
	Segovia
	Hospital General de Segovia
		Hernández José Mariano	Principal Investigator
	Sevilla
	Hospital Universidad Virgen Del Rocio
		Parody Ricardo, Dr	Principal Investigator
	Tarragona
	Hospital Universitari de Tarragona Joan XXIII
		Escoda Lourdes, Dr
		Escoda Lourdes	Principal Investigator
	Tenerife
	Hospital Universitario de Canarias
		Miguel Teodoro Hernández, Dr
	Toledo
	Hospital Nuestra Senora del Prado
		Solano Fernando, DR	Principal Investigator
	Tortosa
	Hospital de Tortosa Verge de la Cinta
		Font llorenç, Dr
		Font Llorenç, Dr	Principal Investigator
	Valencia
	Hospital Clinico Universitario de Valencia
		Terol Maria José, Dr
		Terol Mª José, Dr	Principal Investigator
	Hospital Francesc de Borja
		Ruiz Mª Angeles, Dr	Principal Investigator
	Hospital General Universitario Valencia
		Montesinos Pau, Dr
		Sanchez Magdalena, Dr	Principal Investigator
	Hospital Universitario Dr. Peset
		Sayas Mª José	Principal Investigator
	Hospital Universitario La Fe
		Sanz Miguel Angel
		Sanz Miguel Angel, Dr	Principal Investigator
	Instituto Valenciano De Oncologia
		Llorente Pablo, Dr	Principal Investigator
	Valladolid
	Universidad de Valladolid
		Fernandez Calvo Francisco, Dr	Principal Investigator
	Valls
	Pius Hospital de Valls
		Herranz Mª José, Dr	Principal Investigator
	Vigo
	Complejo Hospitalario Xeral de Vigo
		Poderós Concepción, Dr
		Poderós Concepción, Dr	Principal Investigator
	Vinaros
	Hospital Comarcal de Vinaros
		Montagud Mario, Dr	Principal Investigator
	Vitoria
	Hospital Txagorritxu
		Guinea Josep Mª, Dr
		Guinea José Mª, Dr	Principal Investigator
	Vizcaya
	Hospital de Galdakao
		Ojanguren Jesús, Dr	Principal Investigator
	Zaragoza
	Hospital Clinico Universitario Lozano Blesa
		Palomera Luis, Dr
		Palomera Luis, Dr	Principal Investigator
	Hospital Universitario Miguel Servet
		Rubio Araceli, Dr	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00504764
Information obtained from ClinicalTrials.gov on July 16, 2008