An open-label phase I/II (proof of concept) trial of an combination of Nilotinib (AMN 107) and RAD001 in patients with acute myeloid leukemia - CAMN107ADE01

Active, not recruiting

Conditions: To determine the rate of hematological response in adult patients with c-kit + AML. state the primary objective of the study

Registration Number: EUCTR2007-000502-70-DE

Lead Sponsor: Technical University of Munich

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

- Patients with:
De novo AML or secondary AML from MDS who are not candidates for
myelosuppressive chemotherapy, or
De novo AML or secondary AML from MDS who have relapsed disease or are
refractory to standard therapy
- Patients at least 18 years or older
- Patients with WHO performance status of 0
to 2 with a life expectancy under treatment of at least 3 months
- Patients must have recovered from prior cytotoxic chemotherapy; treatment with
Hydroxyurea or Ara-C is allowed until 24 hours to first administration of study drug.
- Patients must have a serum creatinine of and total bilirubin - Female patients of childbearing potential must have negative pregnancy test within
7 days before initiation of study drug dosing. Postmenopausal women must be
amenorrheic for at least 12 months to be considered of non-childbearing potential.
Male and female patients of reproductive potential must agree to employ an
effective barrier method of birth control throughout the study and for up to 6
months following discontinuation of study drug.
- Written informed consent obtained according to local guidelines.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Patients with AML FAB M3.
- Patients with an expected doubling of the peripheral blast within one week.
- Patients who had prior allogeneic, syngeneic, or autologous bone marrow
transplant or stem cell transplant less than 2 months previously.
- Impaired cardiac function, including any one of the following:
LVEF < 45% or below the institutional lower limit of the normal range
(whichever is higher) as determined by MUGA scan or echocardiogram
Complete left bundle branch block
Use of a cardiac pacemaker
ST depression of > 1mm in 2 or more leads and/or T wave inversions in 2 or
more contiguous leads
Congenital long QT syndrome
History of or presence of significant ventricular or atrial tachyarrhythmias
Clinically significant resting bradycardia (< 50 beats per minute)
QTc > 450 msec on screening ECG (using the QTcF formula)
Right bundle branch block plus left anterior hemiblock, bifascicular block
Myocardial infarction within 12 months prior to starting otinib
Unstable angina diagnosed or treated during the past 12 months
Other clinically significant heart disease (e.g., congestive heart failure,
uncontrolled hypertension, history of labile hypertension, or history of poor
compliance with an antihypertensive regimen)
- Female patients who are pregnant or breast feeding, or adults of childbearing age
not employing an effective method of birth control.
- Concurrent severe and/or uncontrolled medical or psychiatric condition which may
interfere with the completion of the study.
- Patients who had more than 2 prior regimens for their current relapsed or current
primary refractory disease
- Patients with uncontrolled active infection.
- Patient with any pulmonary infiltrate on the baseline chest X-ray known to be new
in the previous 4 weeks. Prior treatment with any investigational drug within the
preceding 4 weeks
- Chronic treatment with systemic steroids or another immunosuppressive agent
- Uncontrolled brain or leptomeningeal metastases, including patients who continue
to require glucocorticoids for brain or leptomeningeal metastases
- Other malignancies within the past 3 years except for adequately treated
carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
- Other concurrent severe and/or uncontrolled medical disease which could
compromise participation in the study (i.e., uncontrolled diabetes, uncontrolled
hypertension, severe infection, severe malnutrition, unstable angina, or congestive
heart failure - New York Heart Association Class III or IV, ventricular arrhythmias
active ischemic heart disease, myocardial infarction within six months, chronic liver
or renal disease, active upper GI tract ulceration)
- A known history of HIV seropositivity
- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis or on oral anti-vitamin K medication
(except low dose coumarin)
- Women who are pregnant or breast feeding, or women able to conceive and
unwilling to practice an effective method of birth control. (Women of childbearing
potential must have a negative urine or serum pregnancy test within 7 days prior
to administration of RAD001). Oral, imp