Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04518644




Registration number
NCT04518644
Ethics application status
Date submitted
14/08/2020
Date registered
19/08/2020
Date last updated
28/04/2023

Titles & IDs
Public title
Nilotinib, for Patients With CML-CP or CML-AP
Scientific title
Managed Access Program to Provide Access to Nilotinib, for Patients With Imatinib-intolerant and/or Resistant Ph+ Chronic Myelogenous Leukemia (CML) in Chronic Phase or CML in Accelerated Phase
Secondary ID [1] 0 0
CAMN107A2411
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myelogenous Leukemia (CML) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Expanded Access
Description of intervention(s) / exposure
Treatment: Drugs - Nilotinib

Treatment: Drugs: Nilotinib
The recommended dosing of nilotinib is 400 mg orally twice daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes

Eligibility
Key inclusion criteria
1. Age = 18 years

2. One of the diagnoses listed below

- Imatinib resistant Philadelphia chromosome positive CML in chronic phase and the
presence of the following criteria:

- < 15% blasts in peripheral blood or bone marrow

- < 30% blasts plus promyelocytes in peripheral blood and bone marrow

- < 20 % basophils in the peripheral blood

- = 100 x 10^9 / L (= 100,000/mm3) platelets

- No evidence of extramedullary leukemic involvement, with the exception of liver
or spleen

- Imatinib resistant Philadelphia chromosome positive CML in accelerated phase
defined as never in blast crisis before starting treatment with one or more of
the following criteria present within 4 weeks prior to beginning treatment:

- = 15% but < 30% blasts in blood or bone marrow

- = 30% blasts plus promyelocytes in peripheral blood or bone marrow (providing
that <30% blasts present in bone marrow)

- peripheral basophils = 20%

- thrombocytopenia < 100 x 10^9 / L unrelated to therapy

- WHO Performance status of 0, 1, or 2

- Imatinib must be discontinued at least 5 days prior to beginning nilotinib
therapy

- Normal organ, electrolyte and marrow functions as described below:

Potassium = LLN (lower limit of normal) or corrected to within normal limits with
supplements prior to the first dose of investigational medication Total calcium (corrected
for serum albumin) = LLN or correctable with supplements Magnesium = LLN or corrected to
within normal limits with supplements prior to the first dose of investigational medication
AST and ALT = 2.5 x ULN or = 5.0 x ULN if considered due to tumor Alkaline phosphatase =
2.5 x ULN unless considered due to tumor Serum bilirubin = 1.5 x ULN Serum amylase and
lipase = 1.5 x ULN Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance =50 ml/min
(calculated creatinine clearance using Cockcroft formula is acceptable) Serum phosphorous =
LLN or corrected to within normal limits with supplements prior to the first dose of
nilotinib medication Written patient informed consent must be obtained prior to start of
treatment. If consent cannot be expressed in writing, it must be formally documented and
witnessed, ideally via an independent trusted witness. An acceptable alternative (e.g., an
assent form, or consent from a parent or guardian) should be signed for legally incompetent
patients (e.g., children).
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of hypersensitivity to any drugs or metabolites of similar chemical classes as
nilotinib.

2. Previous treatment with any cytotoxic investigational drug =4 weeks prior to beginning
nilotinib. At least 2 weeks must have elapsed since the last dose of hormonal therapy
or any approved or investigational "targeted" kinase inhibitor agent with the
exception of imatinib which must be discontinued at least 5 days prior to beginning
therapy with nilotinib.

3. Impaired cardiac function, including any one of the following:

Inability to determine the QT interval on ECG Complete left bundle branch block Long
QT syndrome or family history of long QT syndrome History of or presence of
significant ventricular or atrial tachyarrhythmias Clinically significant resting
brachycardia (<50 beats per minute) QTc > 450 msec on baseline ECG (using the QTcF
formula). If QTc >450 and electrolytes are not within normal ranges, electrolytes
should be corrected and then the patient rescreened for QTc Myocardial infarction
within 12 months prior to starting nilotinib Other clinically significant heart
disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension).

4. any medications that prolong the QT interval and CYP3A4 inhibitors if the treatment
cannot Use of be either safely discontinued or switched to a different medication
prior to starting treatment. Please see http://crediblemeds.org/index.php for a
comprehensive list of agents that prolong the QT interval

5. Severe and/ or uncontrolled concurrent medical disease that in the opinion of the
treating physicians could cause unacceptable safety risks or compromise compliance
with the compassionate use treatment (e.g. impairment of gastrointestinal (GI)
function or GI disease that may significantly alter the absorption of nilotinib,
ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome,
or small bowel resection, uncontrolled diabetes, )

6. Patients who have undergone major surgery = 2 weeks prior to Visit 1 or who have not
recovered from side effects of such surgery

7. Known Cytopathologically confirmed Central Nervous System infiltration.

8. Use of therapeutic warfarin.

9. Acute or chronic liver or renal disease considered unrelated to tumor.

10. Treatment with any hematopoietic colony-stimulating growth factors = 1 week prior to
starting Nilotinib. Erythropoietin is allowed.

11. Patient who has not recovered from side effects of prior chemotherapy, immunotherapy,
other investigational drugs, wide field radiotherapy, or major surgery. Patient who
has received imatinib < 5 days prior to starting nilotinib or has not recovered from
side effects of therapy. Hydroxyurea is permitted during the first 28 days of
treatment (up to 5 g/day) for a maximum of 7 days.

12. Patient with a history of another primary malignancy that is currently clinically
significant or requires active intervention.

13. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test (> 5 mIU/mL).

14. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, including women whose career, lifestyle, or sexual orientation
precludes intercourse with a male partner and women whose partners have been
sterilized by vasectomy or other means, UNLESS they are using two birth control
methods. The two methods can be a double barrier method or a barrier method plus a
hormonal method.

Adequate barrier methods of contraception include: diaphragm, condom (by the partner),
intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives
include any marketed contraceptive agent that includes an estrogen and/or a progestational
agent.

Study design
Purpose of the study
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
No longer available
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this Cohort Treatment Plan is to allow access to Nilotinib for eligible
patients diagnosed with imatinib-intolerant and/or resistant Philadelphia Chromosome positive
(Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) or Chronic Myelogenous Leukemia
in Accelerated Phase (CML-AP). The patient's Treating Physician should follow the suggested
treatment guidelines and comply with all local health authority regulations.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04518644
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04518644