Ph+/Bcr-Abl+ ALL Imatinib and Nilotinib Rotational Study

Study Overview
=================
Brief Summary
-----------------
This study is an open-label, multicentric, exploratory, single arm, phase II study of adults who are either more than 60 years old, or are unfit for intensive chemotherapy and allo SCT. The patients are treated with NILOTINIB, administered orally twice daily, for 6 weeks (Course A) followed by IMATINIB, administered orally twice daily, for other 6 weeks (Course B).The courses will be repeated (rotated) for a total of 4 times or until relapse, or until it is in the interest of the patients. Prednisone (P) will be administered to all patients for 7-14 days, before TKIs, so as to make it possible to wait for the results of cytogenetic and molecular tests, and to evaluate the response to P alone, hence for another 21 days. Intrathecal therapy (IT) with MTX/AraC/DEX is mandatory, monthly, in patients without clinical-cytologic evidence of meningeal involvement, while in patients with CNS involvement it is performed twice weekly until clearance of leukemic cells, hence once weekly. IM will be administered at the dosage of 600 mg daily (300 mg twice daily) and Nilotinib at the dosage of 800 mg daily (400 mg twice daily) in all courses. All patients are scheduled to receive at least 4 courses of either drugs, for a total of 4 courses (4 x 6 = 24 weeks). After 4 courses, patients are either allowed to continue the treatment until relapse or progression, if it is in their interest, or to discontinue the treatment and receive other therapies.

Official Title
-----------------
Front-line Treatment of Ph Positive (Ph+)/Bcr-Abl Positive Acute Lymphoblastic Leukemia (ALL) With Two Tyrosine Kinase Inhibitors (TKI) (Imatinib and Nilotinib). A Phase II Exploratory Multicentric Study in Elderly Patients and in Patients Unfit for Program of Intensive Therapy and Allogeneic Stem Cell Transplantation. GIMEMA Protocol LAL1408. EudraCT 2009-01327122

Conditions
-----------------
Treatment, Stem Cell Transplantation

Intervention / Treatment
-----------------
* Drug: Nilotinib
* Drug: Imatinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Previously untreated Ph+ ALL more than 60 years old or more than 18 years old, but unfit for program of intensive therapy and allogeneic SCT

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Nilotinib|The dose of NIL is 800 mg daily (400 mg twice daily). It must be adapted according to specific guidelines in case of adverse events (AE). It cannot be increased.|
|Drug: Imatinib|The dose of IM is 600 mg daily (300 mg b.i.d.). It must be adapted according to specific guidelines in case of AE. It cannot be increased.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival (DFS) |  | at 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Hematological Response (CHR) rate |  | at 6, 12 and 24 weeks | 
| Complete Cytogenetic Response (CCgR) rate |  | at 6, 12 and 24 weeks and duration of CCgR | 
| Complete molecular response rate (CMR) |  | at 12 and 24 weeks and duration of CMolR | 
| Type and number of BCR-ABL kinase domain mutations |  | developing during and after the study | 
| Relationship between the response, biomarkers and gene expression profile (GEP) |  | At the end of study | 
| Event-Free Survival (EFS) and Overall Survival (OS) |  | defined as the time from the 1st dose of corticosteroids to death or last contact | 
| Side effects, adverse events (AE) and serious AE (SAE) |  | At the end of study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Untreated Ph+ ALL unfit for intense therapy and allo SCT