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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02001818




Registration number
NCT02001818
Ethics application status
Date submitted
12/11/2013
Date registered
5/12/2013
Date last updated
20/05/2014

Titles & IDs
Public title
Pegylated Interferon Alfa-2b and Nilotinib for Augmentation of Complete Molecular Response in Chronic Myeloid Leukaemia
Scientific title
Phase II Study of Nilotinib Plus Pegylated Interferon Alfa-2b as First-line Therapy in Chronic Phase Chronic Myelogenous Leukaemia Aiming to Maximize Complete Molecular Response and Major Molecular Response.
Secondary ID [1] 0 0
ACTRN12612000851864
Secondary ID [2] 0 0
CML11
Universal Trial Number (UTN)
Trial acronym
PInNACLe
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukaemia 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
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nilotinib, Pegylated interferon alpha-2b, Imatinib

Experimental: Nilotinib or Imatinib with Peginterferon - Nilotinib 300mg twice daily for 24 months. Pegylated interferon alpha-2b 30-50 micrograms subcutaneously once weekly for maxium 21 months (3 months after trial registration).
Patients intolerant of nilotinib may be switched to appropriate doses of imatinib


Treatment: Drugs: Nilotinib, Pegylated interferon alpha-2b, Imatinib
All patients joining the study will receive treatment with oral nilotinib at 300mg twice daily. This will be given as monotherapy for 3 months initially, prior to commencement of combination therapy with Pegylated interferon alpha-2b added to nilotinib. Patients intolerant of nilotinib will have the option of switching to imatinib.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
level of BCR-ABL
Timepoint [1] 0 0
24 months of treatment

Eligibility
Key inclusion criteria
All of the following criteria must be satisfied for enrolment in the study.

1. Post-pubertal male or female patients aged 18 years or above.

2. Newly diagnosed (within Three months of study entry) Ph+ CML-Chronic Phase with a
quantifiable "breakpoint cluster region - Abelson murine leukemia" (BCR-ABL)
transcript

3. No prior therapy for CML and no other current anti-leukaemic therapies (other than
prior or current treatment with hydroxyurea or anagrelide).

4. No signs of extramedullary leukaemia, except for hepatosplenomegaly.

5. Documented chronic-phase CML as defined by:

i. <15% blasts in both the peripheral blood and bone marrow ii. <30% blasts and
promyelocytes in both the peripheral blood and bone marrow iii. <20% basophils in the
peripheral blood iv. Platelet count >100 × 109/L (Note: Patients will be considered to
be in chronic phase if their platelet count is = 100 x 109/L as a result of treatment
with hydroxyurea or anagrelide provided that all of the other criteria for chronic
phase CML are met).

6. Eastern Cooperative Oncology Group Performance Status score =2 (see Appendix 2)

7. Patients must have the following laboratory values:

1. Potassium level > Lower Limit of Normal (LLN)

2. Calcium (corrected for serum albumin) > Lower Limit of Normal (LLN)

3. Magnesium level > Lower Limit of Normal (LLN)

4. Phosphorus > Lower Limit of Normal (LLN)

5. ALT and AST < 2.5 × ULN or < 5.0 × Upper limit of normal (ULN) if considered due
to tumour

6. ALP < 2.5 × Upper limit of normal (ULN) unless considered due to tumour

7. Bilirubin < 1.5 × Upper limit of normal (ULN) unless due to Gilbert's syndrome

8. Creatinine < 1.5 × Upper limit of normal (ULN)

9. Amylase and lipase < 1.5 × Upper limit of normal (ULN) Note: Biochemical
abnormalities that resolve after corrective measures pose no impediment to
re-screening.

a) Female patients of childbearing potential must have a negative serum pregnancy test
within one week prior to study entry OR have been amenorrhoeic for at least 12 months.

b) All patients of reproductive potential must agree to use birth control for the duration
of the study. This is only required for as long as the patient has reproductive potential.
The type of birth control is a decision which should be made between the treating clinician
and the patient.

9.Life expectancy of more than 12 months. 10.Patient has given written, informed consent to
participate in the study (which includes consent to obtain samples for the correlative
study except in a rare case where a site does not have the capacity to participate in the
correlative study).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Presence of any of the following criteria will exclude the subject from enrolment in the
study.

1. Patients who have previously received radiotherapy to >25% of their bone marrow.

2. Patients who have undergone major surgery within the 4 weeks prior to study entry or
have not recovered from earlier surgery.

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

1. Inability to monitor the QT/corrected QT intervak (QTc) interval on ECG

2. Long QT syndrome or a known family history of long QT syndrome.

3. Resting bradycardia (<50 beats per minute) suspected to be secondary to cardiac
pathology

4. QTc > 450 msec on baseline ECG (using the QTc formula). If QTc >450 msec and
electrolytes are not within normal ranges, electrolytes should be corrected and
then the patient re-screened for QTc

5. Other clinically significant uncontrolled heart disease (e.g. congestive heart
failure or uncontrolled hypertension)

6. History of or presence of clinically significant ventricular or atrial
tachyarrhythmias, including atrial fibrillation

4. History of arterial vascular disease including coronary artery disease (Angina,
myocardial infarction), cerebrovascular disease (Transient ischaemic attacks and
strokes), peripheral vascular disease, retinal artery thromboses and mesenteric
arterial thromboses.

5. Treatment with agents (other than warfarin) that prolong QT interval or inhibit
Cytochrome P450 3A4 (CYP3A4), unless judged to be clinically essential.

6. Another primary malignant disease, except for such conditions that do not currently
require treatment, lesions that can be or had been completely excised (eg Skin
Cancers) and neoplasms that does not significantly affect long term survival of the
patient

7. Significantly impaired GI function or GI disease that may alter nilotinib absorption.

8. Other concurrent uncontrolled medical conditions (e.g. uncontrolled diabetes,
uncontrolled or unstable thyroid disease, active or uncontrolled infections, acute or
chronic liver and renal disease) that could cause unacceptable safety risks or
compromise compliance with the protocol.

9. History of confirmed acute or chronic pancreatitis.

10. Cytopathologically confirmed Central Nervous System(CNS) infiltration. [In the absence
of suspicion of CNS involvement, lumbar puncture is not required.]

11. Patients unwilling or unable to comply with protocol and patients with a history of
noncompliance or inability to grant informed consent.

12. Known diagnosis of human immunodeficiency virus (HIV) infection.

13. Prior allogeneic stem cell transplantation

14. Patients who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control. Male and female patients of
childbearing potential must agree to employ an effective method of birth control
throughout the study. The type of birth control is a decision which should be made
between the treating clinician and the patient

15. Known history of uncontrolled depression or any other psychiatric disease likely to be
exacerbated by study treatment. A formal psychiatric assessment at baseline is not
required.

16. Current participation in another therapeutic clinical trial (participation in clinical
trials that do not involve active interventions is not an exclusion for the study.)

17. Previous adverse reaction to the trial drug/s

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2021
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Other
Name
Australasian Leukaemia and Lymphoma Group
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Novartis Pharmaceuticals
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The treatment of CML and the expected survival has been revolutionised since the introduction
of tyrosine kinase inhibitors (TKIs) such as nilotinib. Despite their effectiveness, these
drugs will never totally remove CML affected cells from the body. In order to achieve this
goal, and potentially enable CML patients to live without the daily need for TKIs, other
features of the patient's immune system may need to be harnessed. One possibility is using
externally administered interferon (IFN) to augment the response induced by the TKI.

This study will assess the response in terms of length of survival, detection of minimal
disease levels and time until disease worsens in patients with chronic phase CML who are
taking nilotinib and pegylated Interferon. Patients will commence taking nilotinib for 3
months, and once tolerated, will simultaneously be treated with injected pegIFN for up to 2
years. Patients can continue taking nilotinib beyond this time providing they are receiving
benefit. Options are available for patients to decrease or increase their dose or to switch
to another TKI, imatinib, to ensure a balance between drug effectiveness and minimal side
effects is achieved.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02001818
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tim Hughes, MBBS, MD, FRACP, FRCPA
Address 0 0
Royal Adelaide Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Megan Sanders, PhD
Address 0 0
Country 0 0
Phone 0 0
+61 3 9656 9015
Fax 0 0
Email 0 0
megan.sanders@petermac.org
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02001818