Safety and Efficacy of Pegylated IFN-alpha 2B Added to Dasatinib in Newly Diagnosed Chronic Phase Myeloid Leukemia (NordCML007)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01725204
Recruitment Status : Completed
First Posted : November 12, 2012
Last Update Posted : September 25, 2017
Information provided by (Responsible Party):
Norwegian University of Science and Technology

Brief Summary:

Patients with newly diagnosed CML have excellent outcomes with tyrosine kinase inhibitors (TKI). However, a few patients will be cured with TKIs alone, and thus need continued life-long treatment. Some patients achieve complete molecular remission (CMR), and this rate is higher with second generation TKIs compared with imatinib. Some experience with drug discontinuation in CMR has been derived from a few small studies, most notably the French STIM study. Approximately 40 % of patients with a minimum of two years in MR4.5 (4.5 log reduction in molecular response) can stop imatinib without relapse, indicating possible cure. To increase the non-relapse rate is of major importance. To achieve a permanent "cure" without stem cell transplantation is presently the most relevant goal of clinical studies in CML.

The investigators hypothesize that to significantly increase cure rates in CML, therapy should eradicate leukemic stem cells and/or induce or restore anti-CML immunity. Second generation TKIs may have a more profound effect on the stem cell pool as compared to imatinib. This is assessed in our current randomized study with a reduction in leukemic stem cell burden as the primary endpoint (NordCML006). Interferon-alpha (IFN) has a prominent immunomodulatory and antiproliferative mode of action, and has also activity in stem cells. Pegylated IFN in combination with imatinib results in improved therapy responses as compared to imatinib monotherapy. This advantage may translate into higher cure rates.

Dasatinib has a unique dual mechanism of action: it is the most potent of available TKIs and induces immunological effects that are different from those of IFN. Both of these drugs may have immunological adverse-effects when used as a monotherapy. However, immunological adverse-effects may also be markers of anti-leukemia efficacy. A combination of dasatinib and pegylated IFN (PegIFN) may have additive or synergistic effects and should be tested in a clinical study.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Chronic-Phase Drug: Dasatinib + PegIFN Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety and Efficacy Study of Adding Low Dose Pegylated IFN-alpha 2B to Standard Dose Dasatinib in Patients With Newly Diagnosed Chronic Phase Myeloid Leukemia
Actual Study Start Date : September 2012
Primary Completion Date : May 2016
Study Completion Date : May 2016

Arm Intervention/treatment
Experimental: Dasatinib + PegIFN
Dasatinib 100mg OD for three months single drug, with subsequent addition of PegIFN 15 μg/ week for 3 months. If well tolerated (less than grade 2 non-hematological or grade 3 hematological AE) the dose should be increased to 25μg weekly for the remaining 9 months on combination treatment. Thereafter dasatinib will be given as monotherapy. Patients will be followed for 24 months totally.
Drug: Dasatinib + PegIFN

Primary Outcome Measures :
  1. major molecular response rates [ Time Frame: 1 year ]
    defined as ≤0.1% BCR-ABL1 on the MMR International Scale

Secondary Outcome Measures :
  1. overall survival [ Time Frame: 2 years ]
  2. quality of life [ Time Frame: up to 18 months (after 3, 6, 12, 18 months) ]
  3. Rate of CCgR [ Time Frame: up to 18 months (after 3, 6, 12 and 18 months) ]
  4. Rate of MR4.0 and MR4.5 [ Time Frame: up to 24 months (after 3, 6, 12, 15, 18, and 24 months) ]

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of chronic myeloid leukemia in chronic phase (CML-CP) associated with BCR-ABL1 quantifiable by RQ-PCR (IS)
  • No other current or planned anti-leukemia therapies excluding hydroxyurea treatment for up to two months.
  • ECOG Performance status 0,1, or 2
  • Adequate organ function as defined by: Total bilirubin < 1.5 x ULN (ULN = upper limit of normal in a local institution lab) in absence of Gilbert genotype; ASAT and ALAT < 2.5 x ULN. Creatinine < 2x ULN. Potassium, magnesium and phosphate not below LLN (LLN= lower level of normal)
  • Life expectancy of more than 12 months in the absence of any intervention
  • Patient has given written informed consent to participate in the study

Exclusion Criteria:

  • Prior accelerated phase or blast crisis
  • Uncontrolled or significant cardiovascular disease, including any of the following:

    • A myocardial infarction within 6 months
    • Uncontrolled angina within 3 months
    • Congestive heart failure within 3 months
    • Diagnosed or suspected congenital long QT syndrome
    • Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointe)
    • Prolonged QTcF interval > 450 msec on pre-entry ECG
  • Atypical BCR-ABL1 transcript not quantifiable by RQ-PCR.
  • Another primary malignant disease, which requires systemic treatment (chemotherapy or radiation) Severe and/or life-threatening medical disease including acute liver disease
  • History of significant congenital or acquired bleeding disorder unrelated to cancer
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dasatinib
  • Patients actively receiving therapy with strong CYP3A4 inhibitors and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug
  • Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug
  • Female patients who are: pregnant, breast feeding or potentially fertile without a negative pregnancy test prior to baseline or unwilling to use contraception on trial
  • Previous history of pericarditis or pleuritis
  • History of non-compliance, abuse of alcohol, illicit drugs, severe psychiatric disorders or other inability to grant informed consent.
  • Current treatment for depression.
  • Hypersensitivity to any interferon preparation;
  • Autoimmune hepatitis or a history of autoimmune disease;
  • Pre-existing thyroid disease unless it can be controlled with conventional treatment;
  • Epilepsy and/or compromised central nervous system (CNS) function;
  • HCV/HIV patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01725204

Helsinki University Central Hospital
Helsinki, Finland
Bergen University Central Hospital
Bergen, Norway
Oslo, Norway
Stavanger University Hospital
Stavanger, Norway
University Hospital of Northern Norway
Tromsø, Norway
St Olavs Hospital - Trondheim University Hospital
Trondheim, Norway
Linköping University Hospital
Linköping, Sweden
Sunderby Sjukhus
Luleå, Sweden
Lund University Hospital
Lund, Sweden
Karolinska University Hospital
Stockholm, Sweden
Sundsvall County Hospital
Sundsvall, Sweden
Umeå University Hospital
Umeå, Sweden
Uppsala University Hospital
Uppsala, Sweden
Örebro University Hospital
Örebro, Sweden
Sponsors and Collaborators
Norwegian University of Science and Technology
Study Chair: Henrik Hjorth-Hansen, MD PhD Norwegian University of Science and Technology

Publications of Results:
Responsible Party: Norwegian University of Science and Technology Identifier: NCT01725204     History of Changes
Other Study ID Numbers: NordCML007
2011-005989-38 ( EudraCT Number )
First Posted: November 12, 2012    Key Record Dates
Last Update Posted: September 25, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Norwegian University of Science and Technology:
Protein Kinase Inhibitors
pegylated IFN-alpha 2B

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs