Clinical trial NCT02888977: Tyrosine Kinase Inhibitors and Low Intensity Chemotherapy in Ph+ ALL
Official title: An Observatory for Patients Aged 55 Years and Over With Philadelphia Chromosome Positive (Ph+ or BCR-ABL+) Acute Lymphoblastic Leukemia (ALL) and Treated With the Combination of Tyrosine Kinase Inhibitors and Low Intensity Chemotherapy.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lymphoblastic Leukemia, Acute
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2016-09-05
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All consecutive previously untreated patients aged 55 years and over with Philadelphia positive acute lymphoblastic leukaemia (Ph+ ALL) not included in a prospective clinical trial and treated with the combination of TKIs and low-intensity chemotherapy (EWALL backbone see Appendix 1) should be recorded in each center.

Brief summary: The use of imatinib in combination 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. Dasatinib is indicated as first line therapy in Ph+ ALL. Results from the EWALLPH-01 are supporting the use of dasatinib in combination with low-intensity chemotherapy. A new EWALL-PH-02 study combining nilotinib in combination with low-intensity chemotherapy is currently initiated within the EWALL centers.

3. The EWALL-PH-01 trial is now closed after the recruitment of 71 patients. The activation of the EWALL-PH-02 trial is expected for Q1 2012. Based on the recruitment of the EWALL-PH-01 study it could be anticipated that 50 to 100 patients aged more than 55 years will be diagnosed during this 6 months period of time. In addition, all the EWALL centers are not participating to the EWALL-PH-02 study and thus these centers could be offered to treat patient following the EWALL backbone in addition to imatinib. 4. A minimum data set will be defined in order to collect the data of the patients treated following the EWALL-PH imatinib study. The main recommendation is to follow as close as possible the procedures of the EWALL-PH-01 trial (mutation analysis, MRD follow-up) in order to have a comparable data set. This imatinib treated cohort of patients would be of particular importance in order to better define the potential benefit of using one TKI compared to one other. From the end of the EWALL-PH-01 study recruitment to the initiation of the EWALL-PH-02 study, patients were treated following the common backbone schedule in combination with imatinib or others TKI. Patients not included in clinical trials for other reasons were also offered a treatment with the combination of TKIs and backbone low-intensity chemotherapy. The goal of this observatory retrospective and prospective is to describe the efficacy and the tolerance of the combination of tyrosine kinase inhibitors in combination with low intensity chemotherapy (EWALL backbone) in patients with Ph+ ALL aged 55 years and over.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients ≥ 55 years
2. Philadelphia chromosome or BCR-ABL positive acute lymphoblastic leukaemia
3. Not included in a prospective clinical trial
4. Treatment with the combination of tyrosine kinase inhibitors and low dose chemotherapy as recommended by the EWALL group (EWALL backbone).

Exclusion Criteria:

1. Patients deceded and having previously refused data collection.

Primary outcomes:
measure: The primary end-point will be Progression Free Survival (PFS) rate at 12 months
timeFrame: 12 months
Secondary outcomes:
measure: The proportion of Complete haematological remission
timeFrame: 12 months
measure: The proportion of Major molecular response defined by a BCR-ABL/ABL ≤ 0.1% in bone marrow
timeFrame: 12 months
measure: The proportion of Complete molecular response
timeFrame: 12 months
measure: Event free survival
timeFrame: 12 months
measure: Relapse free survival
timeFrame: 12 months
measure: Progression free survival
timeFrame: 12 months
measure: The proportion of Detection of a T315I or F317 BCR-ABL TK mutation
timeFrame: 12 months
measure: The proportion of molecular progression defined by the loss of major molecular response
timeFrame: 12 months
measure: Overall survival
timeFrame: 12 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 12 months
Other outcomes:
Locations:
city: Le Chesnay
country: France
facility: CH Versailles
city: Nimes
country: France
facility: CHU Nimes
city: Reims
country: France
facility: CH Reims
Study officials:
affiliation: CH Versailles
name: Rousselot philippe, MD
role: PRINCIPAL_INVESTIGATOR
References: