Status:
TERMINATED
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
Lead Sponsor:
University Health Network, Toronto
Collaborating Sponsors:
Novartis Pharmaceuticals
Conditions:
Acute Myeloid Leukemia
Eligibility:
All Genders
18-65 years
Phase:
PHASE1
PHASE2
Brief Summary
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 w...
Eligibility Criteria
Inclusion
- AML as defined by WHO (World Health Organization) criteria, all subtypes except APL (acute promyelocytic leukemia).
- One of the following poor risk features:
- Persistent leukemia (at least 10% bone marrow blasts) after induction therapy, consisting of cytarabine 100-200 mg/m2 plus an anthracycline.
- Relapse within two years of achieving complete remission with such induction therapy. Any consolidation therapy is acceptable, including stem cell transplantation.
- No prior inductions, but antecedent myeloproliferative disorder or CMML (chronic myelomonocytic leukemia) (These patients are given NOVE-HiDAC as frontline therapy at Princess Margaret Hospital).
- Positivity for c-kit (CD117) in at least 30% of blasts as measured by flow cytometry. For relapsed patients, this will be assessed at the time of relapse. For primary induction failures the initial diagnostic sample may be used.
- Age 18-65.
- ECOG performance status \< 3 (see Appendix I).
- Patients must have the following laboratory values within normal limits (WNL) at the local institution lab or corrected to WNL with supplements prior to first dose of study medication.
- Potassium (WNL)
- Magnesium (WNL)
- No chemotherapy within the previous four weeks, other than hydroxyurea to control counts. Hydroxyurea may be continued up to Day 4 of treatment with nilotinib. If hydroxyurea is used, it must be stopped at least 48 hours prior to starting chemotherapy.
- Able to give informed consent.
Exclusion
- Active uncontrolled infection.
- Active CNS (central nervous system) leukemia
- Serum creatinine \> 200 umol/L.
- Serum bilirubin \> 1.5 x ULN, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) \> 2x ULN (upper limit of normal).
- Serum amylase and lipase \> 1.5x ULN
- Left ventricular ejection fraction \< 50%
- Impaired cardiac function including any of the following:
- Long QT syndrome or a known family history of long QT syndrome
- History or presence of clinically significant ventricular or atrial tachyarrhythmias
- Clinically significant resting bradycardia (\< 50 beats per minute)
- Inability to monitor the QT interval by ECG
- QTc \> 450 msec on baseline ECG (electrocardiogram). If QTc \> 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
- Myocardial infarction within 1 year of starting study drug
- Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
- Patients currently receiving treatment with strong CYP3A4 inhibitors as listed in Section 5.8 and treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
- Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
- History of acute or chronic pancreatic disease.
- Women who are pregnant, breast feeding, or of childbearing potential without a negative serum test at baseline. Male or female patients of childbearing potential unwilling to use contraceptive precautions throughout the trial and 3 months following discontinuation of study drug. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative serum pregnancy test prior to the first dose of nilotinib.
- Known hypersensitivity to study drugs or other components.
Key Trial Info
Start Date :
October 1 2010
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 1 2015
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT01222143
Start Date
October 1 2010
End Date
April 1 2015
Last Update
June 22 2015
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9