Clinical Trials /

Pegylated Interferon Alfa-2b and Nilotinib for Augmentation of Complete Molecular Response in Chronic Myeloid Leukaemia

NCT02001818

Description:

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.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pegylated Interferon Alfa-2b and Nilotinib for Augmentation of Complete Molecular Response in Chronic Myeloid Leukaemia
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: CML11
  • SECONDARY ID: ACTRN12612000851864
  • NCT ID: NCT02001818

Conditions

  • Chronic Myeloid Leukaemia

Interventions

DrugSynonymsArms
Nilotinib, Pegylated interferon alpha-2b, ImatinibNilotinib or Imatinib with Peginterferon

Purpose

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 Arms

NameTypeDescriptionInterventions
Nilotinib or Imatinib with PeginterferonExperimentalNilotinib 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
  • Nilotinib, Pegylated interferon alpha-2b, Imatinib

Eligibility Criteria

        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).

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:level of BCR-ABL
Time Frame:24 months of treatment
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Australasian Leukaemia and Lymphoma Group

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