Malaysia Stop Tyrosine Kinase Inhibitor Trial

NCT02381379 | Unknown Phase 3

• 1 other identifier: NMRR-13-1186-15491
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Leukemia, Chronic Myeloid

Keywords

CML; peginterferon; stop; BCR-ABL

Outcome Measures

Primary Outcomes (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.

  3 years

Secondary Outcomes (4)

• The number of patients who developed adverse side-effects of interferon

  1 year

• The rate of reattaining deep MR

  3 years

• Time to regain deep MR after relapse

  3 years

• Quality of life (QoL) assessment

  3 year

Study Arms (2)

Peginterferon-α-2a (Pegasys®)

ACTIVE COMPARATOR

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

Drug: Peginterferon-α-2a

Observation

NO INTERVENTION

Stop 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.

Interventions

Peginterferon-α-2a DRUG

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

Also known as: Pegasys®

Peginterferon-α-2a (Pegasys®)

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ministry of Health, Malaysia: lead

Study Sites (9)

Sultanah Aminah Hospital

Johor Bahru, Johor, 80100, Malaysia

Location

Sultanah Bahiyah Hospital

Alor Star, Kedah, 05460, Malaysia

Location

Queen Elizabeth Hospital

Kota Kinabalu, Sabah, Malaysia

Location

Sarawak General Hospital

Kuching, Sarawak, 93586, Malaysia

Location

Miri Hospital

Miri, Sarawak, 98000, Malaysia

Location

Sibu Hospital

Sibu, Sarawak, 96000, Malaysia

Location

Ampang Hospital

Ampang, Selangor, 68000, Malaysia

Location

Malacca General Hospital

Malacca, 75400, Malaysia

Location

Hospital Pulau Pinang

Pulau Pinang, Malaysia

Location

Related Publications (12)

• 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.

  PMID: 20965785 BACKGROUND

• 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.

  PMID: 20811403 BACKGROUND

• 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.

  PMID: 12569603 BACKGROUND

• 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.

  PMID: 21175313 BACKGROUND

• 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.

  PMID: 16424660 BACKGROUND

• 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.

  PMID: 11773172 BACKGROUND

• 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.

  PMID: 14978932 BACKGROUND

• 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.

  PMID: 22395358 BACKGROUND

• 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.

  PMID: 22044951 BACKGROUND

• 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.

  PMID: 22169779 BACKGROUND

• 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.

  PMID: 18385749 BACKGROUND

• 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.

  PMID: 19884523 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

peginterferon alfa-2a

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

Study Officials

• Kian Meng Chang, FRCP(London)

  Ampang Hospital, Malaysia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 6, 2015
• Study Start: March 1, 2015
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2021
• Last Updated: September 14, 2020

Record last verified: 2020-09

Locations

MY (9)