Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
RATIONALE: Nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving nilotinib together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving nilotinib together with combination chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Tasigna® (Nilotinib) Plus Multi-Agent Chemotherapy for Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia|
- Proportion of Patients Achieving Hematologic and Molecular Complete Remission (CR) After Induction Therapy [ Time Frame: 1 month ] [ Designated as safety issue: No ]approximate time: at the recovery of cytopenia
- Disease(Relapse)-Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||January 2009|
|Study Completion Date:||July 2014|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Patients who were Philadelphia-positive, newly-diagnosed adult ALL and treated with nilotinib + mVPD treatment plan
- 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 lineage leukemia.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00844298
|Korea, Republic of|
|Daegu Catholic University Hospital|
|Daegu, Korea, Republic of|
|Daegu Fatima Hospital|
|Daegu, Korea, Republic of, 701-600|
|Kyungpook National University Hospital|
|Daegu, Korea, Republic of, 702-701|
|Yeungnam University Medical Center|
|Daegu, Korea, Republic of, 712-749|
|National Cancer Center - Korea|
|Goyang, Korea, Republic of, 410-769|
|Chonnam National University Hwasun Hospital|
|Jeollanam-do, Korea, Republic of, 519-809|
|Gyeongsang National University Hospital|
|Jinju, Korea, Republic of, 660-701|
|Pusan National University Hospital|
|Pusan, Korea, Republic of, 602-739|
|Seoul National University Hospital|
|Seoul, Korea, Republic of, 110-744|
|Inje University Seoul Paik Hospital|
|Seoul, Korea, Republic of, 100-032|
|Konkuk University Medical Center|
|Seoul, Korea, Republic of, 143-729|
|Kyung Hee University Hospital|
|Seoul, Korea, Republic of, 130-702|
|Samsung Medical Center|
|Seoul, Korea, Republic of, 135-710|
|Asan Medical Center - University of Ulsan College of Medicine|
|Seoul, Korea, Republic of, 138-736|
|Ajou University Hospital|
|Suwon, Korea, Republic of, 441-749|
|Ulsan University Hospital|
|Ulsan, Korea, Republic of|
|Principal Investigator:||Kyoo H. Lee, MD||Asan Medical Center|