Stem Cell Transplantation, Treatment
Conditions
Keywords
Untreated Ph+ ALL unfit for intense therapy and allo SCT
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.
Interventions
DRUGNilotinib
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.
DRUGImatinib
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.
Sponsors
Gruppo Italiano Malattie EMatologiche dell'Adulto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-Free Survival (DFS) | at 24 months |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Complete Hematological Response (CHR) rate | at 6, 12 and 24 weeks |
| 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 |
| Relationship between the response, biomarkers and gene expression profile (GEP) | At the end of study |
Countries
Italy
Outcome results
None listed