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

Chronic Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01564836
• Other study ID #: KC10ENME0465
• Status: Recruiting
• Phase: N/A
• First received: March 26, 2012
• Last updated: January 10, 2014
• Start date: June 2010

Study information

• Verified date: January 2014
• Source: Seoul St. Mary's Hospital
• Contact: Sahee Park, MS
• Phone: +82-2-2258-7030
• Email: saheepark[@]catholic.ac.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Complete Molecular Response
• Imatinib
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul

Sponsors (2)

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

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Probability of persistent undetectable molecular residual disease (UMRD) and MR4.5	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.	12 months	No