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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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:
Condition category
Condition code

Intervention/exposure
Study type
Expanded Access
Description of intervention(s) / exposure
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/study/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/study/NCT04518644