Chemotherapy and Imatinib in Young Adults With Acute Lymphoblastic Leukemia Ph (BCR-ABL) POSITIVE

NCT ID: NCT01491763

Last Updated: 2022-01-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2022-12-31

Brief Summary

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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.

Detailed Description

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Induction Chemotherapy

* Vincristine (VCR): 1.5 mg/m2 (maximum dose 2 mg) iv days 1, 8, 15 and 22
* daunorubicin (DNR) 45 mg/m2 i.v. days 1, 8, 15 and 22
* Prednisone (PDN): 60 mg/m2 per day, i.v. or p.o., days 1-27
* Imatinib 600 mg p.o. from day 1 until the beginning of the consolidation. Important Note: The administration of imatinib be initiated as soon as the outcome of cytogenetic and molecular study, which will be known under normal conditions during prophase consolidation

Patients should be in RC and shall be a minimum of 2 weeks of finding it. Patients did not discontinue treatment with imatinib during this period. Minimum counts to start the consolidation are: neutrophils\> 1x109 / L and platelets\> 100x109 / L.

* Mercaptopurine (MP) 50 mg/m2, p.o. days 1 to 7, 28 to 35 and 56 to 63
* MTX: 1.5 g/m2, i.v. continuous infusion for 24 hours on days 1, 28 and 56.
* VP-16: 100 mg/m2 every 12 hours, i.v. (1 hour infusion) on days 14 and 42
* ARA-C: 1000 mg/m2 every 12 hours, i.v. (3-hour infusion) days 14-15 and 42-43
* triple intrathecal treatment days 1, 28 and 56
* Imatinib 600 mg / d po, from day 1 to 15 days before the TPH.

During consolidation therapy is recommended in primary prophylaxis with G-CSF or found neutropenia (\<0.5 x109 / L). This factor was administered daily until the neutrophil count is \> 1x109 / L in two consecutive measurements. Alternatively, PEG-filgrastim can be used (eg 16 and 44), at the discretion of each center

Allogenic THP or Autologous TPH

Conditions

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Acute Lymphoblastic Leukemia Ph Positive

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Imatinib

600 mg p.o. from day 1 until consolidation

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PETHEMA Foundation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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H. Son Llatzer

Palma de Mallorca, Balearic Islands, Spain

Site Status RECRUITING

Hospital Germans Trias i Pujol and all Hospital Pethema

Badalona, Barcelona, Spain

Site Status RECRUITING

Hospital de Mataró

Mataró, Barcelona, Spain

Site Status RECRUITING

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Canary Islands, Spain

Site Status RECRUITING

Hospital general de Castellón

Castelló, Castellón, Spain

Site Status RECRUITING

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, La Coruña, Spain

Site Status RECRUITING

Clínica Universitaria de Navarra

Pamplona, Navarre, Spain

Site Status RECRUITING

Hospital de Navarra

Pamplona, Navarre, Spain

Site Status RECRUITING

Hospital Central de Asturias

Oviedo, Principality of Asturias, Spain

Site Status RECRUITING

Hospital General de Albacete

Albacete, , Spain

Site Status RECRUITING

Hospital de Alcorcón

Alcorcón, , Spain

Site Status RECRUITING

Hospital General de Alicante.

Alicante, , Spain

Site Status RECRUITING

Hospital de Cabueñes

Asturias, , Spain

Site Status RECRUITING

Hospital de Badalona Germans Trias i Pujol

Badalona, , Spain

Site Status RECRUITING

Hospital Clinic y Provincial de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital Clínico y Provincial de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital de la Santa Creu i Sant Pau.

Barcelona, , Spain

Site Status RECRUITING

Hospital de la Santa Creu i Sant Pau.

Barcelona, , Spain

Site Status RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Hospital de la santa Creu i Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Hospital del Mar

Barcelona, , Spain

Site Status RECRUITING

Hospital del Mar

Barcelona, , Spain

Site Status RECRUITING

Hospital del Mar

Barcelona, , Spain

Site Status RECRUITING

Hospital Duran i Reynals - ICO L'Hospitalet

Barcelona, , Spain

Site Status RECRUITING

Basurtuko Ospitalea

Basurto, , Spain

Site Status RECRUITING

Complejo Hospitalario de Cáceres

Cáceres, , Spain

Site Status RECRUITING

Complejo Hospitalario Reina Sofía

Córdoba, , Spain

Site Status RECRUITING

Area Hospitalaria Juan Ramón Jimenez

Huelva, , Spain

Site Status RECRUITING

Hospital Juan Ramón Jiménez

Huelva, , Spain

Site Status RECRUITING

Hospital del SAS de Jerez de la Frontera

Jerez de la Frontera, , Spain

Site Status RECRUITING

Hospital general de Jerez de la Frontera

Jerez de la Frontera, , Spain

Site Status RECRUITING

Hospital Arnau de Vilanova

Lleida, , Spain

Site Status RECRUITING

Complexo Hospitalario Xeral-Calde

Lugo, , Spain

Site Status RECRUITING

Clínica La Concepción

Madrid, , Spain

Site Status RECRUITING

Clínica Puerta de Hierro

Madrid, , Spain

Site Status RECRUITING

Hospital 12 de Octubre. Madrid

Madrid, , Spain

Site Status RECRUITING

Hospital Clinico San Carlos

Madrid, , Spain

Site Status RECRUITING

Hospital Clínico San Carlos de Madrid

Madrid, , Spain

Site Status RECRUITING

Hospital Clínico San Carlos de Madrid

Madrid, , Spain

Site Status RECRUITING

Hospital de Fuenlabrada

Madrid, , Spain

Site Status RECRUITING

Hospital de la Princesa

Madrid, , Spain

Site Status RECRUITING

Hospital de Madrid, S.A.- Norte Hospital General

Madrid, , Spain

Site Status RECRUITING

Hospital Gregorio Marañón

Madrid, , Spain

Site Status RECRUITING

Hospital Ramón y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario de la Princesa

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Princcipe de Asturias

Madrid, , Spain

Site Status RECRUITING

Althaia, Xarxa Asistencial de Manresa

Manresa, , Spain

Site Status RECRUITING

. Hospital Clínico Universitario Virgen de la Victoria

Málaga, , Spain

Site Status RECRUITING

. Hospital Clínico Universitario Virgen de la Victoria

Málaga, , Spain

Site Status RECRUITING

Hospital Carlos Haya

Málaga, , Spain

Site Status RECRUITING

Hospital Carlos Haya

Málaga, , Spain

Site Status RECRUITING

Hospital Carlos Haya

Málaga, , Spain

Site Status RECRUITING

Hospital de Mérida

Mérida, , Spain

Site Status RECRUITING

Hospital General Univeristario Morales Messeguer

Murcia, , Spain

Site Status RECRUITING

Hospital Sta. Maria del Rosell

Murcia, , Spain

Site Status RECRUITING

Hospital del Río Carrión

Palencia, , Spain

Site Status RECRUITING

Hospital de Gran Canaria Doctor Negrín

Palma de Gran Canaria, , Spain

Site Status RECRUITING

Clínica Universitaria de Navarra

Pamplona, , Spain

Site Status RECRUITING

Hospital de Montecelo

Pontevedra, , Spain

Site Status RECRUITING

Corporació Sanitaria Parc Taulí

Sabadell, , Spain

Site Status RECRUITING

Hospital Clínico de Salamanca

Salamanca, , Spain

Site Status RECRUITING

Hospital Clínico Universitario de Salamanca

Salamanca, , Spain

Site Status RECRUITING

Hospital Clínico Universitario

Salamanca, , Spain

Site Status RECRUITING

Hospital de Donostia

San Sebastián, , Spain

Site Status RECRUITING

Hoaspital Marqués de Valdecilla

Santander, , Spain

Site Status RECRUITING

Hospital General de Segovia

Segovia, , Spain

Site Status RECRUITING

Complejo Hospitalario Regional Virgen del Rocío

Seville, , Spain

Site Status RECRUITING

Hospital Joan XIII de

Tarragona, , Spain

Site Status RECRUITING

Hospital Joan XXIII

Tarragona, , Spain

Site Status RECRUITING

Hospital Clínico de Valencia.

Valencia, , Spain

Site Status RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status RECRUITING

Hospital Clínico Universitario

Valencia, , Spain

Site Status RECRUITING

Hospital Clínic

Valencia, , Spain

Site Status RECRUITING

Hospital Dr Pesset

Valencia, , Spain

Site Status RECRUITING

Hospital La Fe

Valencia, , Spain

Site Status RECRUITING

Hospital Universitario Dr. Peset

Valencia, , Spain

Site Status RECRUITING

Hospital Clínico de Valladolid

Valladolid, , Spain

Site Status RECRUITING

Complejo Hospitalario Xeral-Cies

Vigo, , Spain

Site Status RECRUITING

Hospital do Meixoeiro

Vigo, , Spain

Site Status RECRUITING

Hospital Txagorritxu

Vitoria-Gasteiz, , Spain

Site Status RECRUITING

Hospital Clínico Lozano Blesa

Zaragoza, , Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Josep Mª Ribera, Dr

Role: CONTACT

34 93 497 89 74

Facility Contacts

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Jose Mª Ribera, Dr

Role: primary

Bosch LLobet, Dr

Role: primary

González Brito Gloria, Dr

Role: primary

García Raimundo, Dr

Role: primary

Bello José Luis, Dr

Role: primary

Prosper Felipe, Dr

Role: primary

Perez Equiza Encarnación, Dr

Role: primary

Carrera Dolores, Dr

Role: primary

Peñalver Francisco, Dr

Role: primary

Rivas Concha, Dra

Role: primary

Esteve Jordi, Dr

Role: primary

Rovira Montse, Dr

Role: primary

Sierra Jordi, Dr

Role: primary

Jordi Sierra, Dr

Role: primary

Sureda Anna, Dr

Role: primary

Delgado Julio, Dr

Role: primary

Salar Antonio, Dr

Role: primary

Besses Carles, Dr

Role: primary

Dr. Rafael Duarte Palomino, Dr

Role: primary

Beltran de Heredia José Mª, Dr

Role: primary

Bergua Juan Miguel, Dr

Role: primary

Torres Antonio, Dr

Role: primary

Fernández Antonio, Dr

Role: primary

Fernández Antonio, Dr

Role: primary

Angel León, Dr

Role: primary

León Angel, Dr

Role: primary

Sanchez Juan Manuel, Dr

Role: primary

Román Alejandro, Dr

Role: primary

Nicolás Manuel, Dr

Role: primary

Lahuerta juan José, Dr

Role: primary

Martínez Rafael, Dr

Role: primary

Del Potro Eloy, Dr

Role: primary

Diaz Mediavilla Joaquin, Dr

Role: primary

Adrián Alegre, Dr

Role: primary

Pintado Tomás, Dr

Role: primary

Blanchard Mª Jesús, Dr

Role: primary

De la Cámara Rafael, Dr

Role: primary

Gema Ramirez

Role: primary

Cuesta Angeles, Dr

Role: primary

Bethancourt Concepción, Dr

Role: primary

Barrios Manuel, Dr

Role: primary

Felipe de Arriba, Dr

Role: primary

Ortega Frenando, Dr

Role: primary

Javier Pérez Calvo, Dr

Role: primary

San Miguel Jesús, Dr

Role: primary

Mateos Maria Victoria, Dr

Role: backup

Hernández Rivas José Mª, Dr

Role: primary

Mª Consuelo del Cañizo, Dr

Role: primary

Marín Julián, Dr

Role: primary

Conde Eulogio, Dr

Role: primary

Hernandez José, Dr

Role: primary

Martín Sánchez Jesús, Dr

Role: primary

Natalia Rodriguez, Dr

Role: primary

Escoda Lourdes, Dr

Role: primary

Tormo Mar, Dra

Role: primary

Solano Carlos, Dr

Role: primary

Hernández Juan Carlos, Dr

Role: primary

Terol Maria José, Dr

Role: primary

Ferrer Secundino, Dr

Role: primary

De la Rubia Javier, Dr

Role: primary

Rafecas Javier, Dr

Role: primary

Poderós Concepción, Dr

Role: primary

Guinea Josep Mª, Dr

Role: primary

Olivé Maite, Dr

Role: primary

References

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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.

Reference Type DERIVED
PMID: 31012967 (View on PubMed)

Related Links

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Other Identifiers

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LAL Ph-2008

Identifier Type: -

Identifier Source: org_study_id

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