Safety and Efficacy Study of Nilotinib Combined With Mitoxantrone, Etoposide, and High-dose Cytarabine Induction Chemotherapy Followed by Consolidation for Patients With C-kit Positive Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT01222143|
Recruitment Status : Terminated
First Posted : October 18, 2010
Last Update Posted : June 22, 2015
This is a phase I/II open-label study that is evaluating the toxicity and efficacy of nilotinib combined with mitoxantrone, etoposide, and high-dose cytarabine (NOVE-HiDAC) chemotherapy for patients with poor-risk acute myeloid leukemia (AML). There are two parts to the study. The first part (Phase I) will determine the maximum dose of nilotinib that can safely be given when combined with NOVE-HiDAC. This dose will then be used in combination with the NOVE-HiDAC regimen in the second part of the study (Phase II), which will evaluate the antileukemic activity of the treatment. The patients who achieve complete remission from the induction therapy (1 cycle) will then receive consolidation therapy combined with nilotinib (maximum of 2 cycles).
The patient population for this study will have AML and will fall into a poor risk category. This means they have persistent leukemia after induction therapy, they relapse within two years of achieving complete remission with induction therapy, or they have certain poor risk features at diagnosis. The AML cells will also be positive for c-kit (a stem cell factor receptor), which is involved in cancer cell growth. Nilotinib is a drug that blocks the effects of c-kit. Using this drug in combination with chemotherapy may improve ability of the chemotherapy drugs to kill leukemia cells. This may then increase the chances of the leukemia going into complete remission.
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: NOVE-HiDAC Drug: Nilotinib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study Evaluating the Safety and Efficacy of Nilotinib Combined With Mitoxantrone, Etoposide, and High-Dose Cytarabine (NOVE-HiDAC) Induction Chemotherapy Followed by Consolidation Therapy for Poor-Risk Patients With C-kit Positive Acute Myeloid Leukemia (AML) up to Age 65|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||April 2015|
|Actual Study Completion Date :||April 2015|
Experimental: NOVE-HiDAC and Nilotinib
All patients will be receiving nilotinib combined with mitoxantrone, etoposide and high-dose cytarabine reinduction therapy. Patients achieving complete remission will receive consolidation therapy with nilotinib combined with high-dose cytarabine and mitoxantrone.
NOVE-HiDAC consists of mitoxantrone, etoposide, and modified high-dose cytarabine. During induction patients will receive mitoxantrone by IV on Days 6-10, etoposide by IV on Days 6-10 and cytarabine by IV on Days 11-12.
During consolidation patients will be receiving mitoxantrone by IV on Days 1-10 and cytarabine by IV on Days 6, 8 and 10.
The dose of nilotinib will be determined according to a dose escalation design. There will be three dose levels used in the study.
During induction, nilotinib will be given orally on Days 1-12.
During consolidation, nilotinib will be given orally on Days 1-10.
- To determine the maximum tolerated dose (MTD) of nilotinib when combined with the NOVE-HiDAC regimen (mitoxantrone, etoposide, and modified high-dose cytarabine). [ Time Frame: 2 years ]To determine the maximum tolerated dose (MTD) of nilotinib combined with mitoxantrone, etoposide, and modified high-dose cytarabine (NOVE-HiDAC) induction chemotherapy followed by consolidation chemotherapy for patients with poor risk c-kit positive AML.
- To evaluate the toxicity of the treatment regimen. [ Time Frame: 2 years ]
- To determine the complete response (CR) rate of this combination at the maximum tolerate dose (MTD) of nilotinib. [ Time Frame: 2 years ]
- To determine the disease-free survival of this combination. [ Time Frame: 2 years ]
- To evaluate the pharmacodynamic effects of nilotinib on pERK and pAKT (phosphorylated ERK and AKT) in AML cells in vivo. [ Time Frame: 2 years ]
- To correlate clinical responses with the degree of pAKT and pERK inhibition achieved in vivo. [ Time Frame: 2 years ]
- To correlate the degree of pAKT and pERK inhibition with nilotinib pharmacokinetics. [ Time Frame: 2 years ]
- To correlate pAKT and pERK inhibition with c-kit mutations. [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01222143
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Joseph M Brandwein, MD, FRCPC||Princess Margaret Hospital, Canada|