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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by PETHEMA Foundation
Sponsor:
Information provided by (Responsible Party):
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT01491763
First received: December 12, 2011
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia Ph Positive
Drug: Imatinib
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • Efficacy in terms of number of complete response [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: January 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Imatinib
    600 mg p.o. from day 1 until consolidation
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

  Eligibility

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01491763

Contacts
Contact: Josep Mª Ribera, Dr 34 93 497 89 74 jribera@iconcologia.net

  Show 81 Study Locations
Sponsors and Collaborators
PETHEMA Foundation
  More Information

No publications provided

Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT01491763     History of Changes
Other Study ID Numbers: LAL Ph-2008
Study First Received: December 12, 2011
Last Updated: November 19, 2013
Health Authority: Spain: Ministry of Health

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014