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

Acute Lymphoblastic Leukemia Ph Positive Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01491763
• Other study ID #: LAL Ph-2008
• Status: Recruiting
• Phase: Phase 4
• Start date: January 2008
• Est. completion date: December 2022

Study information

• Verified date: January 2022
• Source: PETHEMA Foundation
• Contact: Josep Mª Ribera, Dr
• Phone: 34 93 497 89 74
• Email: jribera[@]iconcologia.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia Ph Positive
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Imatinib
600 mg p.o. from day 1 until consolidation

Locations

Country	Name	City	State
Spain	Hospital General de Albacete	Albacete
Spain	Hospital de Alcorcón	Alcorcón
Spain	Hospital General de Alicante.	Alicante
Spain	Hospital de Cabueñes	Asturias
Spain	Hospital de Badalona Germans Trias i Pujol	Badalona
Spain	Hospital Germans Trias i Pujol and all Hospital Pethema	Badalona	Barcelona
Spain	Hospital Clinic y Provincial de Barcelona	Barcelona
Spain	Hospital Clínico y Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital de la santa Creu i Sant Pau	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau.	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau.	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Duran i Reynals - ICO L'Hospitalet	Barcelona
Spain	Basurtuko Ospitalea	Basurto
Spain	Complejo Hospitalario de Cáceres	Cáceres
Spain	Hospital general de Castellón	Castello	Castellón
Spain	Complejo Hospitalario Reina Sofía	Córdoba
Spain	Area Hospitalaria Juan Ramón Jimenez	Huelva
Spain	Hospital Juan Ramón Jiménez	Huelva
Spain	Hospital del SAS de Jerez de la Frontera	Jerez de la Frontera
Spain	Hospital general de Jerez de la Frontera	Jerez de la Frontera
Spain	Hospital Arnau de Vilanova	Lleida
Spain	Complexo Hospitalario Xeral-Calde	Lugo
Spain	Clínica La Concepción	Madrid
Spain	Clínica Puerta de Hierro	Madrid
Spain	Hospital 12 de Octubre. Madrid	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Clínico San Carlos de Madrid	Madrid
Spain	Hospital Clínico San Carlos de Madrid	Madrid
Spain	Hospital de Fuenlabrada	Madrid
Spain	Hospital de la Princesa	Madrid
Spain	Hospital de Madrid, S.A.- Norte Hospital General	Madrid
Spain	Hospital Gregorio Marañón	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario Princcipe de Asturias	Madrid
Spain	. Hospital Clínico Universitario Virgen de la Victoria	Málaga
Spain	. Hospital Clínico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Carlos Haya	Málaga
Spain	Hospital Carlos Haya	Málaga
Spain	Hospital Carlos Haya	Málaga
Spain	Althaia, Xarxa Asistencial de Manresa	Manresa
Spain	Hospital de Mataró	Mataró	Barcelona
Spain	Hospital de Mérida	Mérida
Spain	Hospital General Univeristario Morales Messeguer	Murcia
Spain	Hospital Sta. Maria del Rosell	Murcia
Spain	Hospital Central de Asturias	Oviedo	Asturias
Spain	Hospital del Río Carrión	Palencia
Spain	Hospital de Gran Canaria Doctor Negrín	Palma De Gran Canaria
Spain	H. Son Llatzer	Palma de Mallorca	Baleares
Spain	Clínica Universitaria de Navarra	Pamplona	Navarra
Spain	Clínica Universitaria de Navarra	Pamplona
Spain	Hospital de Navarra	Pamplona	Navarra
Spain	Hospital de Montecelo	Pontevedra
Spain	Corporació Sanitaria Parc Taulí	Sabadell
Spain	Hospital Clínico de Salamanca	Salamanca
Spain	Hospital Clínico Universitario	Salamanca
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
Spain	Hospital de Donostia	San Sebastián
Spain	Hoaspital Marqués de Valdecilla	Santander
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela	La Coruña
Spain	Hospital General de Segovia	Segovia
Spain	Complejo Hospitalario Regional Virgen del Rocío	Sevilla
Spain	Hospital Joan XIII de	Tarragona
Spain	Hospital Joan XXIII	Tarragona
Spain	Hospital Universitario de Canarias	Tenerife	Canarias
Spain	Hospital Clínic	Valencia
Spain	Hospital Clínico de Valencia.	Valencia
Spain	Hospital Clínico Universitario	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Dr Pesset	Valencia
Spain	Hospital La Fe	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Spain	Hospital Clínico de Valladolid	Valladolid
Spain	Complejo Hospitalario Xeral-Cies	Vigo
Spain	Hospital do Meixoeiro	Vigo
Spain	Hospital Txagorritxu	Vitoria
Spain	Hospital Clínico Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy in terms of number of complete response		1 year

External Links

•   Pethema Foundation