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

NCT02001818 | Completed Phase 2 DMC

• 2 other identifiers: CML11ACTRN12612000851864
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Myeloid Leukaemia

Outcome Measures

Primary Outcomes (1)

• level of BCR-ABL

  24 months of treatment

Study Arms (1)

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

Drug: Nilotinib, Pegylated interferon alpha-2b, Imatinib

Interventions

Nilotinib, Pegylated interferon alpha-2b, Imatinib DRUG

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.

Nilotinib or Imatinib with Peginterferon

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Australasian Leukaemia and Lymphoma Group: lead
• Merck Sharp & Dohme LLC: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib; peginterferon alfa-2b; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Tim Hughes, MBBS, MD, FRACP, FRCPA

  Royal Adelaide Hospital

  PRINCIPAL INVESTIGATOR

• Andrew Grigg, MBBS, MD, FRACP, FRCPA

  Austin Hospital, Melbourne Australia

  PRINCIPAL INVESTIGATOR

• David Yeung, BSc(Med), MBBS(Hons),FRACP

  SA Pathology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2013
• First Posted: December 5, 2013
• Study Start: April 11, 2014
• Primary Completion: January 7, 2022
• Study Completion: January 7, 2022
• Last Updated: August 6, 2024

Record last verified: 2024-08

Locations

AU (1)