Tasigna® (Nilotinib) Plus Multi-Agent Chemotherapy for Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
- To determine the clinical efficacy of nilotinib and combination chemotherapy, in terms
of hematologic and molecular complete remission (CR) rates, in patients with newly
diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia or acute mixed
- To establish the prognostic factors for patients treated with this regimen.
- To determine the duration of CR in patients treated with this regimen.
- To determine the duration of progression-free and overall survival of these patients.
- To determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to age (15 to 64
years vs ≥ 65 years).
- Induction therapy: Patients receive daunorubicin hydrochloride IV continuously over 24
hours on days 1-3, vincristine sulfate IV on days 1 and 8, and oral prednisolone on
days 1-14. Patients undergo bone marrow examination on day 14. Patients in hematologic
remission proceed to consolidation therapy. Patients with residual leukemic cells > 5%
receive an additional dose of daunorubicin hydrochloride IV continuously over 24 hours
on day 15 before proceeding to consolidation therapy.
- Consolidation therapy: For course 1, patients receive daunorubicin hydrochloride IV
continuously over 24 hours on days 1 and 2, vincristine sulfate IV on days 1 and 8, and
oral prednisolone on days 1-14. For courses 2 and 4, patients receive cytarabine IV
over 2 hours and etoposide IV over 3 hours on days 1-4. For courses 3 and 5, patients
receive methotrexate IV continuously over 36 hours on days 1, 2, 15, and 16 and
leucovorin calcium IV every 6 hours for 3 doses and then orally until blood
methotrexate levels are in a safe range.
Patients also receive oral nilotinib twice daily beginning on day 8 of induction therapy and
continuing until the completion of consolidation therapy.
After completion of consolidation therapy, patients with a hematopoietic stem cell donor
proceed to allogeneic hematopoietic stem cell transplantation (HSCT). Patients who do not
undergo HSCT continue to receive oral nilotinib twice daily for up to 2 years after
completion of consolidation therapy.
After completion of study therapy, patients are followed periodically for up to 1 year.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients achieving hematologic and molecular complete remission (CR) after induction therapy
approximate time: at the recovery of cytopenia
Kyoo H. Lee, MD
Asan Medical Center
South Korea: Korea Food and Drug Administration (KFDA)