Chronic Myeloid LeukaemiaPhase 2PInNACLeNCT02001818
Pegylated Interferon Alfa-2b and Nilotinib for Augmentation of Complete Molecular Response in Chronic Myeloid Leukaemia
A Phase 2 study testing Nilotinib, Pegylated interferon alpha-2b, Imatinib in people with Chronic Myeloid Leukaemia, run by Australasian Leukaemia and Lymphoma Group at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukaemia
- What is being tested?
- Nilotinib, Pegylated interferon alpha-2b, Imatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteAustralia
- Study dates
- 11 Apr 2014to 7 Jan 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All of the following criteria must be satisfied for enrolment in the study.
- Post-pubertal male or female patients aged 18 years or above.
- Newly diagnosed (within Three months of study entry) Ph+ CML-Chronic Phase with a quantifiable "breakpoint cluster region - Abelson murine leukemia" (BCR-ABL) transcript
- No prior therapy for CML and no other current anti-leukaemic therapies (other than prior or current treatment with hydroxyurea or anagrelide).
- No signs of extramedullary leukaemia, except for hepatosplenomegaly.
- Documented chronic-phase CML as defined by:
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- <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).
- Eastern Cooperative Oncology Group Performance Status score ≤2 (see Appendix 2)
- Patients must have the following laboratory values:
- Potassium level > Lower Limit of Normal (LLN)
- Calcium (corrected for serum albumin) > Lower Limit of Normal (LLN)
- Magnesium level > Lower Limit of Normal (LLN)
- Phosphorus > Lower Limit of Normal (LLN)
- ALT and AST < 2.5 × ULN or < 5.0 × Upper limit of normal (ULN) if considered due to tumour
- ALP < 2.5 × Upper limit of normal (ULN) unless considered due to tumour
- Bilirubin < 1.5 × Upper limit of normal (ULN) unless due to Gilbert's syndrome
- Creatinine < 1.5 × Upper limit of normal (ULN)
- Amylase and lipase < 1.5 × Upper limit of normal (ULN) Note: Biochemical abnormalities that resolve after corrective measures pose no impediment to re-screening.
- 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.
- 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).
Who cannot join
- Presence of any of the following criteria will exclude the subject from enrolment in the study.
- Patients who have previously received radiotherapy to >25% of their bone marrow.
- Patients who have undergone major surgery within the 4 weeks prior to study entry or have not recovered from earlier surgery.
- Impaired cardiac function, including any of the following:
- Inability to monitor the QT/corrected QT intervak (QTc) interval on ECG
- Long QT syndrome or a known family history of long QT syndrome.
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- Resting bradycardia (<50 beats per minute) suspected to be secondary to cardiac pathology
- 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
- Other clinically significant uncontrolled heart disease (e.g. congestive heart failure or uncontrolled hypertension)
- History of or presence of clinically significant ventricular or atrial tachyarrhythmias, including atrial fibrillation
- 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.
- Treatment with agents (other than warfarin) that prolong QT interval or inhibit Cytochrome P450 3A4 (CYP3A4), unless judged to be clinically essential.
- 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
- Significantly impaired GI function or GI disease that may alter nilotinib absorption.
- 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.
- History of confirmed acute or chronic pancreatitis.
- Cytopathologically confirmed Central Nervous System(CNS) infiltration. [In the absence of suspicion of CNS involvement, lumbar puncture is not required.]
- Patients unwilling or unable to comply with protocol and patients with a history of noncompliance or inability to grant informed consent.
- Known diagnosis of human immunodeficiency virus (HIV) infection.
- Prior allogeneic stem cell transplantation
- 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
- 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.
- Current participation in another therapeutic clinical trial (participation in clinical trials that do not involve active interventions is not an exclusion for the study.)
- Previous adverse reaction to the trial drug/s
Trial locations and contacts
1 site in 1 country.
About this study
Official 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.
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.
- Conditions
- Chronic Myeloid Leukaemia
- Being tested
- Nilotinib, Pegylated interferon alpha-2b, Imatinib
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nilotinib, Pegylated interferon alpha-2b, ImatinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib or Imatinib with Peginterferon | Experimental | 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 Receives: Drug: Nilotinib, Pegylated interferon alpha-2b, Imatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
level of BCR-ABL
Measured: 24 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2013 (estimated)
- Study start11 Apr 2014
- Primary completion7 Jan 2022
- Study completion7 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Australasian Leukaemia and Lymphoma Group
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Tim Hughes, MBBS, MD, FRACP, FRCPA, Principal investigator, Royal Adelaide HospitalAndrew Grigg, MBBS, MD, FRACP, FRCPA, Principal investigator, Austin Hospital, Melbourne AustraliaDavid Yeung, BSc(Med), MBBS(Hons),FRACP, Principal investigator, SA Pathology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02001818
- Sponsor's protocol ID
- CML11
- Other IDs
- ACTRN12612000851864
- Acronym
- PInNACLe
- Status last verified
- Aug 2024
- First submitted
- 12 Nov 2013
- Last updated
- 6 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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.
- ClinicalTrials.gov ID
- NCT02001818
- Acronym / sponsor ID
- PInNACLe / CML11
- Conditions
- Chronic Myeloid Leukaemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Australasian Leukaemia and Lymphoma GroupUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Novartis Pharmaceuticals
- Study start
- 11 Apr 2014 (actual)
- Primary completion
- 7 Jan 2022 (actual)
- Study completion
- 7 Jan 2022 (actual)
- First posted
- 5 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib or Imatinib with Peginterferon | Experimental | Drug: Nilotinib, Pegylated interferon alpha-2b, ImatinibNilotinib 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- All of the following criteria must be satisfied for enrolment in the study.
- Post-pubertal male or female patients aged 18 years or above.
- Newly diagnosed (within Three months of study entry) Ph+ CML-Chronic Phase with a quantifiable "breakpoint cluster region - Abelson murine leukemia" (BCR-ABL) transcript
- No prior therapy for CML and no other current anti-leukaemic therapies (other than prior or current treatment with hydroxyurea or anagrelide).
- No signs of extramedullary leukaemia, except for hepatosplenomegaly.
Key exclusion criteria (24 listed)
- Presence of any of the following criteria will exclude the subject from enrolment in the study.
- Patients who have previously received radiotherapy to >25% of their bone marrow.
- Patients who have undergone major surgery within the 4 weeks prior to study entry or have not recovered from earlier surgery.
- Impaired cardiac function, including any of the following:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nilotinib, Pegylated interferon alpha-2b, ImatinibAll 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. | Drug | Nilotinib or Imatinib with Peginterferon |
Primary outcome
level of BCR-ABL
Time frame: 24 months of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tim Hughes, MBBS, MD, FRACP, FRCPA principal investigator
Royal Adelaide Hospital
Andrew Grigg, MBBS, MD, FRACP, FRCPA principal investigator
Austin Hospital, Melbourne Australia
David Yeung, BSc(Med), MBBS(Hons),FRACP principal investigator
SA Pathology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib, Pegylated interferon alpha-2b, Imatinib in people with Chronic Myeloid Leukaemia, run by Australasian Leukaemia and Lymphoma Group at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
level of BCR-ABL (time frame: 24 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.