Phase 2
N=34
Daunorubicin Hydrochloride, Cytarabine, and Nilotinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT01806571 ↗Enrolled (actual)
34
Serious AEs
91.2%
Results posted
Nov 2019
Primary outcome: Primary: Proportion of Complete Responses (CR or CRi) During Induction Therapy — 0.618 proportion of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cytarabine (Drug); Daunorubicin Hydrochloride (Drug); Laboratory Biomarker Analysis (Other); Nilotinib (Drug); Pharmacological Study (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Mayo Clinic
- Primary completion
- Jul 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Proportion of Complete Responses (CR or CRi) During Induction Therapy |
0.618 | — |
| SECONDARY Disease Free Survival(DFS) Rate |
56.4 | — |
| SECONDARY Duration of Complete Response |
NA | — |
| SECONDARY Incidence of Adverse Events as Assessed by NCI CTCAE Version 4.0 |
34 | — |
| SECONDARY Overall Survival(OS) Rate |
70.6 | — |
Summary
This phase II trial studies how well daunorubicin hydrochloride, cytarabine, and nilotinib work in treating patients newly diagnosed with acute myeloid leukemia. Drugs used in chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving daunorubicin hydrochloride with cytarabine and nilotinib may kill more cancer cells.
Eligibility Criteria
Inclusion Criteria
- Untreated, histological confirmed acute myeloid leukemia (AML) based on World Health Organization (WHO) 2008 criteria with Kit expression (cluster of differentiation [CD] 117) of myeloblasts >= 20% by flow cytometry from bone marrow aspirate at diagnosis
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- Magnesium within normal limits (WNL)
- Potassium WNL
- Phosphorus WNL
- Serum amylase = 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
- Myocardial infarction = 5-fold increase in the plasma area under the curve (AUC) values or more than 80% decrease in clearance
- Boceprevir (Victrelis)
- Clarithromycin (Biaxin, Biaxin XL)
- Conivaptan (Vaprisol)
- Grapefruit juice
- Indinavir (Crixivan)
- Itraconazole (Sporanox)
- Ketoconazole (Nizoral)
- Lopinavir/ritonavir (Kaletra)
- Mibefradil
- Nefazodone (Serzone)
- Nelfinavir (Viracept)
- Posaconazole (Noxafil)
- Ritonavir (Novir, Kaletra)
- Saquinivir (Fortovase, Invirase)
- Telaprevir (Incivek)
- Telithromycin (Ketek)
- Voriconazole (Vfend)
- Moderate inhibitors of CYP3A4/5 > 2-fold in the plasma AUC values or 50-80% decrease in clearance
- Amprenavir (Agenerase)
- Aprepitant (Emend)
- Atazanavir (Reyataz)
- Ciprofloxacin (Cipro)
- Darunavir (Prezista)
- Diltiazem (Cardizem, Cardizem CD, Cardizem LA, Cardizem SR, Cartia XT, Dilacor XR, Diltia XT, Taztia XT, Tiazac)
- Erythromycin (Erythrocin, E.E.S. , Ery-Tab, Eryc, EryPed, PCE)
- Fluconazole (Diflucan)
- Fosamprenavir (Lexiva)
- Imatinib (Gleevec)
- Verapamil (Calan, Calan SR, Covera-HS, Isoptin SR, Verelan, Verelan PM)
- Receiving any medications or substances that are inducers of CYP3A4; use of the following inducers are prohibited = 80% decrease in AUC
- Avasimibe
- Carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Tegretol-XR)
- Phenytoin (Dilantin, Phenytek)
- Rifampin (Rifadin)
- St. John's wort
- Moderate inducers of CYP3A4/5 50-80% decrease in AUC
- Bosentan (Tracleer)
- Efavirenz (Sustiva)
- Etravirine (Intelence)
- Modafinil (Provigil)
- Nafcillin
- Nevirapine (Viramune)
- Phenobarbital (Luminal)
- Rifabutin (Mycobutin)
- Troglitazone
- Patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the 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 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery)
- Acute or chronic pancreatic disease
- Known cytopathologically confirmed central nervous system (CNS) infiltration
- Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
- History of significant congenital or acquired bleeding disorder unrelated to cancer
- Major surgery =< 4 weeks prior to registration of the study or who have not recovered from prior surgery
- Treatment with other investigational agents =< 14 days of registration
- Diagnosis of AML-M3 (or acute promyelocytic leukemia)
Data sourced from ClinicalTrials.gov (NCT01806571). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.