Clinical Trials Logo

Clinical Trial Summary

1. The use of imatinib in combination or in association with chemotherapy is now considered as the gold standard for the treatment of Ph+ ALL. The complete remission (CR) rate is 90% versus 20% to 40% with chemotherapy alone. The combination of imatinib, vincristine and dexamethasone is a well tolerated regimen in aged patients and is also associated with a high CR rate of 80% to 90% in patient aged 55 years and over.

2. However, despite high CR rates, the progression free survival rate at 12 months of patients treated with the combination of imatinib and chemotherapy is 30% to 50%. Relapses remain frequent and only patients intensified with allogenic haematopoietic stem cell transplantation are in long term remission. This strategy is not fully applicable to most patients aged 55 years and over.

3. Relapses after or during imatinib therapy in patients with Ph+ ALL are associated with BCR-ABL tyrosine kinase domain mutation in 80% of cases, predominantly of the p-loop. The exact incidence of the T315I mutation is controversial and can be estimated to be near 50%. Conversely, the detection of the T315I or F317 mutation in a patient is a very strong predictor of relapse.

4. Dasatinib is a potent SCR and BCR-ABL tyrosine kinase inhibitor with preserved in vitro activity in most of the BCR-ABL mutated cell lines, except for the T315I and F317 mutations. This is also the case in vivo, with patients harbouring BCR-ABL TK domain mutations remaining sensitive to dasatinib. The CHR rate in Ph+ ALL resistant to imatinib is 33% and the median progression-free survival is 3.7 months. Progression free survival (PFS) rate at 12 months is 22%.

The goal of this trial is to evaluate the efficacy and the tolerance of the combination of dasatinib with chemotherapy in the front-line setting as induction and consolidation therapy in Ph+ ALL patient aged 55 years and over. A European consensus has been reached to adopt a common chemotherapeutic schedule for patients aged 55 years and over. This schedule will be used in this trial with the addition of dasatinib as concomitant therapy during induction and alternating with chemotherapy during consolidation and maintenance. A CR rate of 90% and a progression free survival of 60% at 12 months are expected. The patients will be prospectively monitored for minimal residual disease and mutation.


Clinical Trial Description

n/a


Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT02888990
Study type Interventional
Source Central Hospital, Versailles
Contact
Status Completed
Phase Phase 2
Start date August 2007
Completion date January 2016

See also
  Status Clinical Trial Phase
Terminated NCT00916045 - Pilot Study of Unrelated Cord Blood Transplantation Phase 2
Completed NCT00458250 - Feasibility of Haploidentical Hematopoietic Stem Cell Transplantation Using CAMPATH-1H Phase 1
Completed NCT02264873 - Phase I, Dose Escalation Study of Decitabine Phase 1
Recruiting NCT01015742 - Unrelated Double Umbilical Cord Blood Units Transplantation Phase 2/Phase 3
Completed NCT00475280 - "Geriatric Assessment Adapted" Therapy for Ph- ALL Elderly Patients Phase 2
Recruiting NCT03331211 - Observation of the Effect of Chemotherapy Combined With Tyrosinase Inhibitor on the Reactivation of CMV and EBV in Patients With Acute Lymphoblastic Leukemia N/A
Terminated NCT01100658 - Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors N/A
Completed NCT00241358 - Study Evaluating AMD3100 for Transplantation of Sibling Donor Stem Cells in Patients With Hematological Malignancies Phase 1/Phase 2
Completed NCT01976442 - Use of Saline-Washed Platelet and Red Cell Transfusions in Adult Acute Leukemia N/A
Recruiting NCT00619879 - Myeloablative Hematopoietic Progenitor Cell Transplantation (HPCT) for Pediatric Malignancies Phase 3
Completed NCT00179764 - Immunoablative Mini Transplant (Hematopoietic Peripheral Blood Stem Cell Transplant [HPBSC]) N/A
Terminated NCT01045382 - MSC and HSC Coinfusion in Mismatched Minitransplants Phase 2
Completed NCT00186901 - A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors Phase 3
Completed NCT00859586 - Mismatched Donor Lymphocyte Infusions for Relapsed Disease Following Allogeneic Stem Cell Transplantation N/A
Terminated NCT00539656 - Transplantation of Umbilical Cord Blood Following Chemotherapy for Blood Cancers Phase 1/Phase 2
Terminated NCT01186328 - EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL) Phase 1
Terminated NCT01158885 - Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia Phase 2
Completed NCT03627208 - Optimal Methods of Disease Detection in Children and Young Adults With Acute Lymphoblastic Leukemia in the Pediatric Oncology Branch
Recruiting NCT03235973 - Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes Phase 1