AzTrials
AzTrials

Leukemia, Chronic MyeloidPhase 3MSITNCT02381379

Malaysia Stop Tyrosine Kinase Inhibitor Trial

A Phase 3 study testing Peginterferon-α-2a in people with Leukemia, Chronic Myeloid, run by Ministry of Health, Malaysia at 9 sites in Malaysia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

To compare administration of peginterferon-α-2a for 1 year versus observation after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukemia (CML) patients with deep MR ≥ 2 years. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Chronic Myeloid
What is being tested?
Peginterferon-α-2a
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
118 participants
Where
9 sitesMalaysia
Study dates
Mar 2015to Oct 2021
Phase
Phase 3
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

  • The subject must be 18 years old or above
  • The subject has CML in chronic phase during diagnosis
  • The subject is treated with ongoing TKI at any dose for at least 3 years
  • The subject has achieved stable deep molecular response (DMR) on International Scale (IS) for 2 years or more by any TKI
  • Definition of deep molecular response (IS) ≥ 2 years
  • Deep molecular response = MR4 (IS 0.01%) or better
Show all 9Show fewer
  • There must be at least 2 results (including the latest) of MR4.5 with an acceptable control gene copy number for the assay over the last two years
  • There must not be any result exceeding a major molecular response (MMR) (IS 0.1%) over the last two years
  • The latest PCR result should be compelled with Intervention Start Date, which is within 4 weeks of Study Entry Date or 17 weeks of the latest PCR test.

Who cannot join

  • The subject has previous history of any TKI failure as according to European LeukemiaNet 2009(17).
  • The subject has previous history of successfully engrafted autologous or allogeneic haematopoeitic stem cell transplant and after transplant no disease relapse as defined by MSIT protocol
  • The subject is planned for autologous or allogeneic stem cell transplantation
  • The subject has previous history of interferon or peginterferon administration and achieved complete cytogenetic response with interferon or peginterferon
  • The subject had undergone or on immune-modulatory treatments other than interferon or peginterferon
  • The subject is undergoing treatment for other malignancies
Show all 12Show fewer
  • The subject has haemoglobin <9g/dL and platelet count <90x109/L for two successive readings of 1 month apart
  • The subject has positive Hepatitis B surface Ag (HBsAg), Hepatitis C antibody (anti-HCV), or Human Immunodeficiency Virus 1 antibody (anti-HIV1)
  • The subject has creatinine clearance of ≤50mL/min
  • The subject has persistent alanine transaminase ≥2x upper normal limit for two successive readings of 1 month apart.
  • Adults under law protection or without ability to consent
  • The subject has previous history or on-going psychiatric illness

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Malaysia9 sites

  • Sultanah Bahiyah Hospital

    Alor Star, Kedah, 05460

  • Ampang Hospital

    Ampang, Selangor, 68000

  • Sultanah Aminah Hospital

    Johor Bahru, Johor, 80100

  • Queen Elizabeth Hospital

    Kota Kinabalu, Sabah

  • Sarawak General Hospital

    Kuching, Sarawak, 93586

  • Malacca General Hospital

    Malacca, 75400

  • Miri Hospital

    Miri, Sarawak, 98000

  • Hospital Pulau Pinang

    Pulau Pinang

  • Sibu Hospital

    Sibu, Sarawak, 96000

Other trials in Malaysia

About this study

Official title: A Randomized Control Trial Comparing Peginterferon-α-2a Versus Observation After Stopping Tyrosine Kinase Inhibitor in Chronic Myeloid Leukemia With Deep Molecular Response for at Least Two Years

To compare administration of peginterferon-α-2a for 1 year versus observation after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukemia (CML) patients with deep MR ≥ 2 years.

Read the detailed description

Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm signified by the presence of Philadephia chromosome, which is the derivative of chromosome 22 after translocation between chromosome 9 and 22. The Philadephia chromosome will produce the mutated tyrosine kinase (BCR-ABL1), which will initiate the pathogenesis of the disease.

Imatinib is the first tyrosine kinase inhibitor (TKI), which has changed the treatment paradigm of CML since its approval from U.S. Food and Drug Administration in 2001 for the treatment of CML. It signifies a new era of oncological treatment using targeted therapy. Subsequent generation TKIs have been marketed as a more potent therapy for CML. Tyrosine kinase inhibitor is conventionally thought not able to cure CML and it has to be taken for life. It is able to induce a very deep molecular response (MR) in about 10% of CML patients as evidenced by persistent undetectable or ≤0.0032% (International Scale IS) BCR-ABL1 transcript in quantitative polymerase chain reaction (PCR) test on current molecular assays, which is labelled as MR4.5 or more. However these patients have to continue taking their TKIs as per recommendations from the European Leukaemia Net and this is the current practice in our institution and in Malaysia. Long term treatment is cumbersome, there is a concern of chronic side effects with long term tyrosine kinase inhibition and it is a financial burden on most countries' health budget as these drugs are very expensive.

Current available data showed that 40% of CML patients with prior stable MR4.5 for 2 years or more will be able to stay imatinib-free for at least 2 years. About 13% of patients without confirmed molecular relapse by the study criteria have low persistent BCR-ABL1 but remain imatinib-free for median follow-up of 22 months (range 6 - 35). A few patients with confirmed molecular relapse by study criteria remained drug free on follow-up. This postulates a component of immunity suppressing the leukemic clone.

Interferon is the standard treatment of CML before the era of TKI. As a single agent, it induces complete cytogenetic response (CCR) in about 20%, and non-sustainable deep MR in about 10% of patients in early chronic phase. These are much smaller figures compared to TKI. Imatinib at the dose of 400mg daily induces CCR in about 70% and deep MR in about 10% of patient in chronic phase after one year of treatment. However, interferon-responded patients may indeed retain the response once interferon was withdrawn via interferon-induced immunity towards the leukemic clone, which leads to longer drug free period compared to TKI. Hence, it is logical to postulate the use of interferon after TKI was stopped when patients have attained deep MR for more than two years will increase the percentage of patients remain TKI-free on follow-up. Unfortunately, there are not many studies concerning this matter. Carella et al described a case series of five patients with deep MR ranging from 12 to 41 months, were put on interferon with follow-up ranging from three to 16 months. Recently, there was a study from Japan, nine out of 12 analyzable patients including 3 patients with previous treatment of interferon, who stopped TKI, was put on interferon remained in deep MR after median follow-up of 23 months (6-27 months). In regards to peginterferon, there is a small studies by Hardan I et al describing 11 CML patients with various responses after imatinib (from complete cytogenetic response N=3, major molecular response N=6, deep MR N=2) were put on peginterferon-α-2a for nine months together with imatinib, then imatinib was stopped and continued with peginterferon-α-2a for another three months. It is difficult to draw any conclusion from this paper because of the small number of subjects, only two subjects have achieved deep MR (with unknown duration) before study entry, and peginterferon-α-2a was combined with imatinib for nine months which will cloud the true effect of peginterferon-α-2a after imatinib was stopped.

So far, there is no randomized study comparing interferon administered for fix duration after TKI was stopped versus observation to see whether the percentage and duration of CML patient who remains TKI-free can be increased and prolonged with interferon, respectively. It will be of interest to see how long the group which was given interferon remains TKI-free. If they remain TKI-free for a long duration, it not only suggests the interferon-induced immunity, but also suggests the interferon-induced immunity can be induced when only a very low level of leukemic cells present. Economical wise, TKI-free certainly give a big relief on the limited health budget of the on-growing CML population.

Being tested
Peginterferon-α-2a
Keywords
CML, peginterferon, stop, BCR-ABL
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.

  • Peginterferon-α-2aDrug

    Also called Pegasys®

    Subcutaneous peginterferon-α-2a (PEGASYS®) starting at 180µg weekly for one year.

Study groups in NCT02381379
Study groupRoleWhat they receive
Peginterferon-α-2a (Pegasys®)Active comparatorSubcutaneous peginterferon-α-2a (PEGASYS®) starting at 180µg weekly for one year
Receives: Drug: Peginterferon-α-2a
ObservationNo interventionStop tyrosine kinase inhibitor that was on and no active medication that might affect CML, for example any immune-modulatory agents, traditional herbs or medications, chemotherapeutic agents, growth factors, or colony stimulating factors is allowed during the trial period.

What is being measured

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

  1. Relapse rate

    Relapse is defined as either i. Loss of MMR, which is a reading of > 0.1% IS, which need to be confirmed by a second analysis point if no previous increasing trend of PCR result, or ii. Positivity of BCR-ABL1 transcripts in quantitative PCR, as confirmed by a second analysis point, indicating the increase (at least 1 log) in relation to the first analysis point at two successive assessments.

    Measured: 3 years

Secondary outcomes (4)

  1. The number of patients who developed adverse side-effects of interferon

    The number of patients who developed adverse side-effects of interferon vs observation arm.

    Measured: 1 year

  2. The rate of reattaining deep MR

    The success rate of reattaining deep MR after restarting TKI in those patients who relapse.

    Measured: 3 years

  3. Time to regain deep MR after relapse

    Defined as time of relapse to the first time point, after restarting whatever treatment, patient has deep MR confirmed by second analysis point.

    Measured: 3 years

  4. Quality of life (QoL) assessment

    Assessed by questionnaire from INTERNATIONAL PROJECT ON QUALITY OF LIFE IN CHRONIC MYELOID LEUKEMIA.

    Measured: 3 year

Timeline

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

  1. First posted6 Mar 2015 (estimated)
  2. Study startMar 2015
  3. Primary completionOct 2018
  4. Study completionOct 2021 (estimated)

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
118 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02381379
Sponsor's protocol ID
NMRR-13-1186-15491
Acronym
MSIT
Status last verified
Sep 2020
First submitted
2 Mar 2015
Last updated
14 Sep 2020
Results posted
No
Data monitoring committee
No

Publications

  • Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiffers J, Rousselot P; Intergroupe Francais des Leucemies Myeloides Chroniques. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 2010 Nov;11(11):1029-35. doi: 10.1016/S1470-2045(10)70233-3. Epub 2010 Oct 19.

    PubMed 20965785

  • Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Bartley PA, Slader C, Field C, Dang P, Filshie RJ, Mills AK, Grigg AP, Melo JV, Hughes TP. Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR. Leukemia. 2010 Oct;24(10):1719-24. doi: 10.1038/leu.2010.185. Epub 2010 Sep 2.

    PubMed 20811403

  • Kantarjian HM, O'Brien S, Cortes JE, Shan J, Giles FJ, Rios MB, Faderl SH, Wierda WG, Ferrajoli A, Verstovsek S, Keating MJ, Freireich EJ, Talpaz M. Complete cytogenetic and molecular responses to interferon-alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer. 2003 Feb 15;97(4):1033-41. doi: 10.1002/cncr.11223.

    PubMed 12569603

  • Preudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, Coiteux V, Gardembas M, Berthou C, Vekhoff A, Rea D, Jourdan E, Allard C, Delmer A, Rousselot P, Legros L, Berger M, Corm S, Etienne G, Roche-Lestienne C, Eclache V, Mahon FX, Guilhot F; SPIRIT Investigators; France Intergroupe des Leucemies Myeloides Chroniques (Fi-LMC). Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010 Dec 23;363(26):2511-21. doi: 10.1056/NEJMoa1004095.

    PubMed 21175313

  • Verbeek W, Konig H, Boehm J, Kohl D, Lange C, Heuer T, Scheibenbogen C, Reis HE, Hochhaus A, Graeven U. Continuous complete hematological and cytogenetic remission with molecular minimal residual disease 9 years after discontinuation of interferon-alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemia. Acta Haematol. 2006;115(1-2):109-12. doi: 10.1159/000089476.

    PubMed 16424660

  • Mahon FX, Delbrel X, Cony-Makhoul P, Faberes C, Boiron JM, Barthe C, Bilhou-Nabera C, Pigneux A, Marit G, Reiffers J. Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa. J Clin Oncol. 2002 Jan 1;20(1):214-20. doi: 10.1200/JCO.2002.20.1.214.

    PubMed 11773172

  • Usuki K, Kanda Y, Iijima K, Iki S, Hirai H, Urabe A. [Chronic myelogenous leukemia in cessation of therapy after sustained CCR with interferon]. Rinsho Ketsueki. 2003 Dec;44(12):1161-5. Japanese.

    PubMed 14978932

  • Mauro E. Long-term molecular response after discontinuation of interferon-alpha in two patients with chronic myeloid leukaemia. Blood Transfus. 2012 Oct;10(4):559; author reply 560. doi: 10.2450/2012.0144-11. Epub 2012 Feb 29. No abstract available.

    PubMed 22395358

  • Veneri D, Tecchio C, De Matteis G, Paviati E, Benati M, Franchini M, Pizzolo G. Long-term persistence of molecular response after discontinuation of interferon-alpha in two patients with chronic myeloid leukaemia. Blood Transfus. 2012 Apr;10(2):233-4. doi: 10.2450/2011.0057-11. Epub 2011 Sep 22. No abstract available.

    PubMed 22044951

  • Hardan I, Stanevsky A, Volchek Y, Tohami T, Amariglio N, Trakhtenbrot L, Koren-Michowitz M, Shimoni A, Nagler A. Treatment with interferon alpha prior to discontinuation of imatinib in patients with chronic myeloid leukemia. Cytokine. 2012 Feb;57(2):290-3. doi: 10.1016/j.cyto.2011.11.018. Epub 2011 Dec 13.

    PubMed 22169779

  • Carella AM. Interferon-alpha is able to maintain complete molecular remission induced by imatinib after its discontinuation. Leukemia. 2008 May;22(5):1090-1. doi: 10.1038/leu.2008.94. Epub 2008 Apr 3. No abstract available.

    PubMed 18385749

  • Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, Cervantes F, Deininger M, Gratwohl A, Guilhot F, Hochhaus A, Horowitz M, Hughes T, Kantarjian H, Larson R, Radich J, Simonsson B, Silver RT, Goldman J, Hehlmann R; European LeukemiaNet. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009 Dec 10;27(35):6041-51. doi: 10.1200/JCO.2009.25.0779. Epub 2009 Nov 2.

    PubMed 19884523

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Peginterferon-α-2a in people with Leukemia, Chronic Myeloid, run by Ministry of Health, Malaysia at 9 sites in Malaysia.

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 9 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 14 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Malaysia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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?

Relapse rate (time frame: 3 years). 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 NCT02381379, which also lists 12 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 14 Sep 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in