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Leukemia, Myeloid, Chronic-PhasePhase 2NordCML007NCT01725204

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

A Phase 2 study testing Dasatinib + PegIFN in people with Leukemia, Myeloid, Chronic-Phase, run by Norwegian University of Science and Technology at 14 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Leukemia, Myeloid, Chronic-Phase
What is being tested?
Dasatinib + PegIFN
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
14 sitesin 3 countries
Study dates
Sep 2012to May 2016
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 23Show fewer
  • 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

Trial locations and contacts

14 sites in 3 countries.

14 sites in 3 countries

Sweden8 sites

  • Linköping University Hospital

    Linköping

  • Sunderby Sjukhus

    Luleå

  • Lund University Hospital

    Lund

  • Örebro University Hospital

    Örebro

  • Karolinska University Hospital

    Stockholm

  • Sundsvall County Hospital

    Sundsvall

  • Umeå University Hospital

    Umeå

  • Uppsala University Hospital

    Uppsala

Other trials in Sweden

Norway5 sites

  • Bergen University Central Hospital

    Bergen

  • Rikshospitalet

    Oslo

  • Stavanger University Hospital

    Stavanger

  • University Hospital of Northern Norway

    Tromsø

  • St Olavs Hospital - Trondheim University Hospital

    Trondheim

Other trials in Norway

Finland1 site

  • Helsinki University Central Hospital

    Helsinki

Other trials in Finland

About this study

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

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.

Being tested
Dasatinib + PegIFN
Keywords
dasatinib, Protein Kinase Inhibitors, pegylated IFN-alpha 2B, Interferon-alpha
Medical subject headings
Leukemia, Myeloid, Chronic-Phase

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dasatinib + PegIFNDrug

Study groups in NCT01725204
Study groupRoleWhat they receive
Dasatinib + PegIFNExperimentalDasatinib 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.
Receives: Drug: Dasatinib + PegIFN

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. major molecular response rates

    defined as ≤0.1% BCR-ABL1 on the MMR International Scale

    Measured: 1 year

Secondary outcomes (4)

  1. overall survival

    Measured: 2 years

  2. quality of life

    Measured: up to 18 months (after 3, 6, 12, 18 months)

  3. Rate of CCgR

    Measured: up to 18 months (after 3, 6, 12 and 18 months)

  4. Rate of MR4.0 and MR4.5

    Measured: up to 24 months (after 3, 6, 12, 15, 18, and 24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Nov 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionMay 2016
  4. Study completionMay 2016

Resources

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
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01725204
Sponsor's protocol ID
NordCML007
Other IDs
2011-005989-38
Acronym
NordCML007
Status last verified
Sep 2017
First submitted
8 Nov 2012
Last updated
25 Sep 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Hjorth-Hansen H, Stentoft J, Richter J, Koskenvesa P, Hoglund M, Dreimane A, Porkka K, Gedde-Dahl T, Gjertsen BT, Gruber FX, Stenke L, Eriksson KM, Markevarn B, Lubking A, Vestergaard H, Udby L, Bjerrum OW, Persson I, Mustjoki S, Olsson-Stromberg U. Safety and efficacy of the combination of pegylated interferon-alpha2b and dasatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients. Leukemia. 2016 Sep;30(9):1853-60. doi: 10.1038/leu.2016.121. Epub 2016 May 2.

    PubMed 27133821

  • Huuhtanen J, Ilander M, Yadav B, Dufva OM, Lahteenmaki H, Kasanen T, Klievink J, Olsson-Stromberg U, Stentoft J, Richter J, Koskenvesa P, Hoglund M, Soderlund S, Dreimane A, Porkka K, Gedde-Dahl T, Gjertsen BT, Stenke L, Myhr-Eriksson K, Markevarn B, Lubking A, Dimitrijevic A, Udby L, Bjerrum OW, Hjorth-Hansen H, Mustjoki S. IFN-alpha with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia. J Clin Invest. 2022 Sep 1;132(17):e152585. doi: 10.1172/JCI152585.

    PubMed 36047494

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dasatinib + PegIFN in people with Leukemia, Myeloid, Chronic-Phase, run by Norwegian University of Science and Technology at 14 sites in 3 countries.

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 6 inclusion and 23 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 25 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Sweden, Norway, Finland. 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?

major molecular response rates (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01725204, which also lists 2 linked publications.

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 25 Sep 2017.

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