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

Sponsor

Seoul St. Mary's Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT01564836

Collaborator

Ministry of Health & Welfare, Korea (Other)

Enrollment

Locations

Arm

Patients Per Site

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia Imatinib Complete Molecular Response	Behavioral: Imatinib treatment discontinuing	N/A

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Jun 1, 2010

Anticipated Primary Completion Date :

Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Probability of persistent undetectable molecular residual disease (UMRD) and MR4.5 [12 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Seoul St. Mary's Hospital	Seoul		Korea, Republic of	137-701
2	Seoul St. Mary's Hospital	Seoul		Korea, Republic of	137-701

Sponsors and Collaborators

Seoul St. Mary's Hospital
Ministry of Health & Welfare, Korea

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Dong-Wook Kim, Professor, Seoul St. Mary's Hospital

ClinicalTrials.gov Identifier:

NCT01564836

Other Study ID Numbers:

KC10ENME0465

First Posted:

Mar 28, 2012

Last Update Posted:

Jan 13, 2014

Last Verified:

Jan 1, 2014

Additional relevant MeSH terms:

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Imatinib Mesylate

Study Results

No Results Posted as of Jan 13, 2014