Discontinuation Study of Imatinib in Adult CP CML Patients Who Have a Complete Molecular Response to Imatinib

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Seoul St. Mary's Hospital
Sponsor:
Collaborator:
Ministry of Health & Welfare, Korea
Information provided by (Responsible Party):
Dong-Wook Kim, Seoul St. Mary's Hospital
ClinicalTrials.gov Identifier:
NCT01564836
First received: March 26, 2012
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

This prospective study is performed to identify safer and more concrete indicators of successful discontinuation and explore contributing factors for sustained undetectable transcript


Condition Intervention
Chronic Myeloid Leukemia
Imatinib
Complete Molecular Response
Behavioral: Imatinib treatment discontinuing

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center Study of the Discontinuation of Imatinib in Adult Patients With Ph+ CML in CP Who Have a Complete Molecular Response to Imatinib

Resource links provided by NLM:


Further study details as provided by Seoul St. Mary's Hospital:

Primary Outcome Measures:
  • Probability of persistent undetectable molecular residual disease (UMRD) and MR4.5 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Our primary objectives were to evaluate the probability of persistent undetectable molecular residual disease (UMRD) and MR4.5 at 12 months after discontinuation, to measure the duration of persistent UMRD and MR4.5 after discontinuation, and to identify contributing factors for sustained undetectable transcript.


Estimated Enrollment: 50
Study Start Date: June 2010
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imatinib treatment discontinuing Behavioral: Imatinib treatment discontinuing
Ph+ CP CML patients who were treated with IM for more than 3 years in sustained MR4.5 or undetectable transcript for at least 2 years are enrolled

Detailed Description:

Imatinib (IM) treatment has been the standard of care for chronic phase (CP) chronic myeloid leukemia (CML) and approximately 50% of CP CML patients who received IM treatment achieve complete molecular response (CMR) at 6-7 years.(Hochhaus A et al. Leukemia 2009;23:1054-1061, Hughes et al. Blood 2008;112:334) The recent data from a study aimed to assess whether IM can be discontinued in patients with a CMR lasting at least 2 years showed the probability of persistent CMR at 12 months was 41%, and suggested IM can be safely discontinued, at least in some patients with sustained CMR. (Mahon et al. Lancet Oncol 2010;11:1029-1035) However, to define whether discontinuation of IM treatment can be safely employed, further validation and much longer follow-up are needed.

Aims This prospective study is performed to identify safer and more concrete indicators of successful discontinuation and explore contributing factors for sustained undetectable transcript.

Primary Objective:

  • To evaluate the probability of persistent undetectable molecular residual disease (UMRD) and MR4.5 at 12 months after discontinuation
  • To measure the duration of persistent UMRD and MR4.5 after discontinuation
  • To identify contributing factors for sustained undetectable transcript

Secondary Objective:

  • To evaluate the probability of major molecular response (MMR) loss
  • To evaluate the time taken to lose MMR at 12 months after discontinuation
  • In patients with loss of MMR, the probability of re-achieving MMR/MR4.5
  • To measure the time taken to re-achieve MMR/MR4.5 after IM resumption
  • To identify contributing factors for sustained re-achieve MMR/MR4.5

Trial Design This is a prospective, multicenter, non-randomised IM discontinuation study.

Response Evaluation After discontinuation, molecular response was monitored using RQ-PCR assay every month up to 6 month follow-up, every 2 months up to 12 month follow-up, and every 3 months thereafter. The loss of MMR, MR4.5, and UMRD were defined on 2 consecutive assessments.

If loss of MMR occurred, IM treatment was re-introduced. Written informed consents were obtained for all patients

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult (≥ 18 years-old) Ph+ CP CML patients who were treated with IM for more than 3 years in sustained MR4.5 or undetectable transcript for at least 2 years are enrolled. MR4.5 or undetectable transcript must be sustained by 2 consecutive RQ-PCR assay within 6 months

Exclusion Criteria:

  • Patients were diagnosed with AP or BP CML
  • Ph+ ALL
  • Received cytotoxic chemotherapy or any other TKIs except imatinib
  • Any evidence of on-going graft versus-host disease (GVHD)
  • Relapsed patients after allogeneic stem cell transplantation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01564836

Contacts
Contact: Sahee Park, MS +82-2-2258-7030 saheepark@catholic.ac.kr

Locations
Korea, Republic of
Seoul St. Mary's Hospital Recruiting
Seoul, Korea, Republic of, 137-701
Contact: Sahee Park, MS    +82-2-2258-7030    saheepark@catholic.ac.kr   
Principal Investigator: Dong-Wook Kim, Professor         
Seoul St. Mary's Hospital Recruiting
Seoul, Korea, Republic of, 137-701
Sponsors and Collaborators
Seoul St. Mary's Hospital
Ministry of Health & Welfare, Korea
  More Information

No publications provided

Responsible Party: Dong-Wook Kim, Professor, Seoul St. Mary's Hospital
ClinicalTrials.gov Identifier: NCT01564836     History of Changes
Other Study ID Numbers: KC10ENME0465
Study First Received: March 26, 2012
Last Updated: January 10, 2014
Health Authority: Korea: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014