Nilotinib-Chemotherapy in CML Myeloid BP or Bcr-abl(+) AML (NICE-BORA)
The current standard therapy in previously untreated adults with chronic phase (CP) of CML is imatinib and the result of long-term follow-up of IRIS study proves that imatinib for CML CP is reasonable therapy.(1, 2) However, some patients were initially diagnosed as advanced CML, accelerated phase (AP) or blastic phase (BP). Various chemotherapies were tried and were found that there were no highly effective chemotherapies for CML BP.(3-11) Imatinib in patients with these advanced CML is also disappointing because of low response rates as well as short response duration, and sudden transformation to BC is found even in initial CML CP patients. (12-17). Recent studies showed that nilotinib or dasatinib is better than imatinib in terms of rapid response and higher molecular response in newly diagnosed CML patients.(18-21) More potent bcr-abl suppression of nilotinib is supposed to be more active than imatinib even in patients with advanced CML. However, nilotinib in patients with imatinib-resistant or -intolerant CML BP showed low hematologic response and major cytogenetic response.(22, 23)
Chronic Myeloid Leukemia in Myeloid Blast Crisis
Untreated Adult Acute Myeloid Leukemia
Drug: Nilotinib+AD induction
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Nilotinib Combined by Chemotherapy for Myeloid Blastic Phase of Chronic Myeloid Leukemia or Bcr-abl Positive Acute Myeloid Leukemia|
- Complete remission rate [ Time Frame: Within 8 weeks after induction therapy ] [ Designated as safety issue: No ]Primary purpose of this study is to define the efficacy of combined chemotherapy and nilotinib in chronic myeloid leukemia (CML) myeloid blastic phase (MBP) and bcr-abl positive acute myeloid leukemia (AML). The efficacy will be evaluated by complete remission (CR) rate.
- Safety [ Time Frame: Within 8 weeks after induction therapy ] [ Designated as safety issue: Yes ]
- This study will also evaluate the safety of nilotinib and chemotherapy combination therapy.
- CTCAE ver. 4.03 will be used for safety measurement.
- Time-dependent variables [ Time Frame: at least 2 years ] [ Designated as safety issue: No ]• This study will evaluate the impacts of nilotinib combined with chemotherapy on duration of CR, relapse-free survival (RFS), event-free survival (EFS), and overall survival (OS).
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
Experimental: Nilotinib+AD induction
Nilotinib plus AD induction chemotherapy
Drug: Nilotinib+AD induction
• Post-remission consolidation chemotherapy
Other Name: Tasigna
- IMATINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE ACUTE LYMPHOBLASTIC LYMPHOMA (PH+ ALL) The trials combining imatinib with high-dose chemotherapy were successfully resulting in high response rate and longer survival and a role for bridging therapy to allogeneic hematopoietic stem cell transplantation (alloHSCT) by means of concurrent or alternating regimen in patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL).(24-29) Current combination therapy of imatinib and chemotherapy became standard therapy of Ph+ ALL and new 2nd generation TKIs are investigating. These experiences may be translated into the treatment of CML BP.
- HIGH-DOSE DAUNORUBICIN IN ACUTE MYELOID LEUKEMIA (AML) INDUCTION CHEMOTHERAPY Two recently published papers of randomized trials comparing standard dose daunorubicin (45 mg/m2 for 3 days) and high dose daunorubicin (90 mg/m2 for 3 days) demonstrated improved CR rate and survival with high dose daunorubicin in younger (60 years or younger) and older (over 60 years) patients, respectively.(30, 31) Therefore high-dose daunorubicin can be applied safely and effectively to the treatment of CML BP.
- NILOTINIB COMBINED WITH CHEMOTHERAPY FOR PHYLADELPHIA POSITIVE CML MYELOID BLASTIC PHASE (MBP) OR PHYLADELPHIA POSITIVE AML We will try 2nd generation TKI, nilotinib and high-dose daunorubicin induction chemotherapy combination to find out the combination therapy can improve response rate and survival in patients with CML MBP.
|Contact: Hawk Kim, M.D., Ph.D.||+firstname.lastname@example.org|
|Contact: Min Jung Kim, R.N.||+email@example.com|
|Korea, Republic of|
|Seoul St Mary's Hospital||Recruiting|
|Seoul, Korea, Republic of|
|Contact: Dong-Wook Kim, M.D., Ph.D. firstname.lastname@example.org|
|Principal Investigator: Dong-Wook Kim, M.D., Ph.D.|
|Ulsan University Hospital||Recruiting|
|Ulsan, Korea, Republic of, 682714|
|Principal Investigator: Hawk Kim, M.D., Ph.D.|
|Sub-Investigator: Jae-Hoo Park, M.D., Ph.D.|
|Sub-Investigator: Jae-Cheol Jo, M.D., Ph.D.|
|Principal Investigator:||Hawk Kim, M.D., Ph.D.||Ulsan University Hospital, University of Ulsan College of Medicine|