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

January 17, 2022 updated by: PETHEMA Foundation

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Anticipated)

70

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Spain
      • Albacete, Spain
        • Recruiting
        • Hospital General de Albacete
      • Alcorcón, Spain
        • Recruiting
        • Hospital de Alcorcón
      • Alicante, Spain
        • Recruiting
        • Hospital General de Alicante.
        • Contact:
          • Rivas Concha, Dra
      • Asturias, Spain
        • Recruiting
        • Hospital de Cabueñes
      • Badalona, Spain
        • Recruiting
        • Hospital de Badalona Germans Trias i Pujol
        • Principal Investigator:
          • Oriol Albert, DR
      • Barcelona, Spain
        • Recruiting
        • Hospital Del Mar
        • Contact:
          • Besses Carles, Dr
        • Principal Investigator:
          • Besses Carles, Dr
      • Barcelona, Spain
        • Recruiting
        • Hospital de la Santa Creu i Sant Pau
        • Contact:
          • Delgado Julio, Dr
        • Principal Investigator:
          • Delgado Julio, Dr
      • Barcelona, Spain
        • Recruiting
        • Hospital Clinic y Provincial de Barcelona
      • Barcelona, Spain
        • Recruiting
        • Hospital Clínico y Provincial de Barcelona
        • Contact:
          • Rovira Montse, Dr
        • Principal Investigator:
          • Rovira Montse, Dr
      • Barcelona, Spain
        • Recruiting
        • Hospital de la Santa Creu i Sant Pau.
        • Contact:
          • Jordi Sierra, Dr
      • Barcelona, Spain
        • Recruiting
        • Hospital Duran i Reynals - ICO L'Hospitalet
        • Contact:
          • Dr. Rafael Duarte Palomino, Dr
      • Basurto, Spain
        • Recruiting
        • Basurtuko Ospitalea
      • Cáceres, Spain
        • Recruiting
        • Complejo Hospitalario de Caceres
      • Córdoba, Spain
        • Recruiting
        • Complejo Hospitalario Reina Sofía
      • Huelva, Spain
        • Recruiting
        • Hospital Juan Ramón Jimenez
      • Huelva, Spain
        • Recruiting
        • Area Hospitalaria Juan Ramón Jimenez
      • Jerez de la Frontera, Spain
        • Recruiting
        • Hospital Del Sas de Jerez de La Frontera
        • Contact:
          • Angel León, Dr
      • Jerez de la Frontera, Spain
        • Recruiting
        • Hospital general de Jerez de la Frontera
        • Contact:
          • León Angel, Dr
        • Principal Investigator:
          • León Angel, Dr
      • Lleida, Spain
        • Recruiting
        • Hospital Arnau de Vilanova
      • Lugo, Spain
        • Recruiting
        • Complexo Hospitalario Xeral-Calde
      • Madrid, Spain
        • Recruiting
        • Hospital Gregorio Marañon
        • Contact:
          • Pintado Tomás, Dr
        • Principal Investigator:
          • Pintado Tomás, Dr
      • Madrid, Spain
        • Recruiting
        • Hospital Clinico San Carlos
      • Madrid, Spain
        • Recruiting
        • Hospital Ramon y Cajal
        • Contact:
          • Blanchard Mª Jesús, Dr
        • Principal Investigator:
          • Blanchard Mª Jesús, Dr
      • Madrid, Spain
        • Recruiting
        • Clínica La Concepción
      • Madrid, Spain
        • Recruiting
        • Clínica Puerta de Hierro
        • Contact:
          • Nicolás Manuel, Dr
        • Principal Investigator:
          • Nicolás Manuel, Dr
      • Madrid, Spain
        • Recruiting
        • Hospital 12 de Octubre. Madrid
      • Madrid, Spain
        • Recruiting
        • Hospital Clínico San Carlos de Madrid
      • Madrid, Spain
        • Recruiting
        • Hospital De Fuenlabrada
        • Principal Investigator:
          • Bravo Barahona Pilar, Dr
      • Madrid, Spain
        • Recruiting
        • Hospital de La Princesa
      • Madrid, Spain
        • Recruiting
        • Hospital de Madrid, S.A.- Norte Hospital General
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario de La Princesa
        • Contact:
          • De la Cámara Rafael, Dr
        • Principal Investigator:
          • de la Cámara Rafael, Dr
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario Princcipe de Asturias
        • Principal Investigator:
          • Burgaleta Carmen, Dr
      • Manresa, Spain
        • Recruiting
        • Althaia, Xarxa Asistencial de Manresa
      • Murcia, Spain
        • Recruiting
        • Hospital General Univeristario Morales Messeguer
        • Contact:
          • Felipe de Arriba, Dr
      • Murcia, Spain
        • Recruiting
        • Hospital Sta. Maria del Rosell
      • Málaga, Spain
        • Recruiting
        • Hospital Carlos Haya
      • Málaga, Spain
        • Recruiting
        • . Hospital Clínico Universitario Virgen de la Victoria
        • Contact:
          • Gema Ramirez
        • Principal Investigator:
          • Ramirez Gema, Dr
      • Mérida, Spain
        • Recruiting
        • Hospital de Mérida
        • Principal Investigator:
          • Lopez Carlos, Dr
      • Palencia, Spain
        • Recruiting
        • Hospital del Río Carrión
      • Palma De Gran Canaria, Spain
        • Recruiting
        • Hospital de Gran Canaria Doctor Negrin
        • Principal Investigator:
          • Suarez Alexia, Dr
      • Pamplona, Spain
        • Recruiting
        • Clinica Universitaria de Navarra
        • Contact:
          • Javier Pérez Calvo, Dr
        • Principal Investigator:
          • Javier Pérez Calvo, Dr
      • Pontevedra, Spain
        • Recruiting
        • Hospital de Montecelo
      • Sabadell, Spain
        • Recruiting
        • Corporacio Sanitaria Parc Tauli
      • Salamanca, Spain
        • Recruiting
        • Hospital Clinico Universitario de Salamanca
        • Contact:
          • Hernández Rivas José Mª, Dr
        • Principal Investigator:
          • Hernández Rivas José Mª, Dr
      • Salamanca, Spain
        • Recruiting
        • Hospital Clinico De Salamanca
      • Salamanca, Spain
        • Recruiting
        • Hospital Clinico Universitario
        • Contact:
          • Mª Consuelo del Cañizo, Dr
        • Principal Investigator:
          • Mª Consuelo del Cañizo, Dr
      • San Sebastián, Spain
        • Recruiting
        • Hospital de Donostia
        • Contact:
          • Marín Julián, Dr
        • Principal Investigator:
          • Marín Julián, Dr
      • Santander, Spain
        • Recruiting
        • Hoaspital Marqués de Valdecilla
        • Contact:
          • Conde Eulogio, Dr
      • Segovia, Spain
        • Recruiting
        • Hospital General de Segovia
        • Contact:
          • Hernandez José, Dr
        • Principal Investigator:
          • Hernández José, Dr
      • Sevilla, Spain
        • Recruiting
        • Complejo Hospitalario regional Virgen del Rocio
      • Tarragona, Spain
        • Recruiting
        • Hospital Joan XIII de
        • Contact:
          • Natalia Rodriguez, Dr
        • Principal Investigator:
          • Natalia Rodriguez, Dr
      • Tarragona, Spain
        • Recruiting
        • Hospital Joan XXIII
      • Valencia, Spain
        • Recruiting
        • Hospital Clinico Universitario
        • Contact:
          • Hernández Juan Carlos, Dr
        • Principal Investigator:
          • Hernández Juan Carlos, DR
      • Valencia, Spain
        • Recruiting
        • Hospital la Fe
      • Valencia, Spain
        • Recruiting
        • Hospital Clínico Universitario de Valencia
        • Contact:
          • Solano Carlos, Dr
        • Principal Investigator:
          • Solano Carlos, Dr
      • Valencia, Spain
        • Recruiting
        • Hospital Clínico de Valencia.
      • Valencia, Spain
        • Recruiting
        • Hospital Clinic
      • Valencia, Spain
        • Recruiting
        • Hospital Dr Pesset
      • Valencia, Spain
        • Recruiting
        • Hospital Universitario Dr. Peset
        • Contact:
          • Rafecas Javier, Dr
        • Principal Investigator:
          • Rafecas Javier, Dr
      • Valladolid, Spain
        • Recruiting
        • Hospital Clínico de Valladolid
      • Vigo, Spain
        • Recruiting
        • Complejo Hospitalario Xeral-Cies
        • Contact:
          • Poderós Concepción, Dr
      • Vigo, Spain
        • Recruiting
        • Hospital Do Meixoeiro
      • Vitoria, Spain
        • Recruiting
        • Hospital Txagorritxu
        • Contact:
          • Guinea Josep Mª, Dr
        • Principal Investigator:
          • Guinea José Mª, Dr
      • Zaragoza, Spain
        • Recruiting
        • Hospital Clinico Lozano Blesa
        • Contact:
          • Olivé Maite, Dr
        • Principal Investigator:
          • Olivé Maite, Dr
    • Asturias
      • Oviedo, Asturias, Spain
        • Recruiting
        • Hospital Central de Asturias
        • Contact:
          • Carrera Dolores, Dr
        • Principal Investigator:
          • Carrera Dolores, Dr
    • Baleares
      • Palma de Mallorca, Baleares, Spain
        • Recruiting
        • H. Son Llàtzer
    • Barcelona
      • Badalona, Barcelona, Spain
        • Recruiting
        • Hospital Germans Trias i Pujol and all Hospital Pethema
      • Mataró, Barcelona, Spain
        • Recruiting
        • Hospital de Mataro
        • Contact:
          • Bosch LLobet, Dr
        • Principal Investigator:
          • Bosch Alba, Dr
    • Canarias
      • Tenerife, Canarias, Spain
        • Recruiting
        • Hospital Universitario de Canarias
        • Contact:
          • González Brito Gloria, Dr
        • Principal Investigator:
          • Gonzalez brito Gloria, Dr
    • Castellón
      • Castello, Castellón, Spain
        • Recruiting
        • Hospital General de Castellon
        • Contact:
          • García Raimundo, Dr
        • Principal Investigator:
          • Garcia Raimundo, Dr
    • La Coruña
      • Santiago de Compostela, La Coruña, Spain
        • Recruiting
        • Complejo Hospitalario Universitario de Santiago
        • Contact:
          • Bello José Luis, Dr
    • Navarra
      • Pamplona, Navarra, Spain
        • Recruiting
        • Clinica Universitaria de Navarra
      • Pamplona, Navarra, Spain
        • Recruiting
        • Hospital de Navarra
        • Contact:
          • Perez Equiza Encarnación, Dr
        • Principal Investigator:
          • Perez Equiza Encarnación, Dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 55 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy in terms of number of complete response
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PETHEMA Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2008

Primary Completion (Anticipated)

December 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

December 12, 2011

First Submitted That Met QC Criteria

December 13, 2011

First Posted (Estimate)

December 14, 2011

Study Record Updates

Last Update Posted (Actual)

January 19, 2022

Last Update Submitted That Met QC Criteria

January 17, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LAL Ph-2008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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