Study of Treatment Free Remission in Patients With Chronic Myeloid Leukemia in Chronic Phase (AST)

Prospective Study of Treatment Free Remission in Patients With Chronic Myeloid Leukemia in Chronic Phase Who Achieved Deep Molecular Response With Tyrosine Kinase Inhibitors in Real Life Setting in Argentina - (Argentine Stop Trial)

The principal aim of this study is to evaluate complete molecular remission in patients with chronic myeloid leukemia (CML) in deep molecular response after stopping tyrosine kinase inhibitor (TKI) treatment. The second aim is to characterize the immunological status of patients with CML at the time of TKI interruption and then at 3 months after the interruption.

Study Overview

• Status: Recruiting
• Conditions: CML
• Intervention / Treatment: Drug: Discontinuing treatment with Tyrosine Kinase Inhibitor after enrolment

Detailed Description

ARGENTINA STOP TRIAL is a multicentre, open-label, uncontrolled trial to estimate the persistence of molecular remission in patients with chronic phase Chronic Myeloid Leukemia (CML) in Deep Molecular Response after stopping Tyrosine Kinase Inhibitor (TKI)

Primary Objective:

- To identify the proportion of patients who continue on Major Molecular Response after discontinuing treatment with TKI.

Secondary objectives:

• To characterize the immunological status of patients with CML at the time of interruption and then at 3 and 12 months after the interruption.

Tertiary objective: To evaluate the pharmacoeconomic impact of interrupting the treatment.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carolina Pavlovsky, MD; Phone Number: +541148771070; Email: cpavlovsky@fundaleu.org.ar
• Study Contact Backup: Name: Mariana Juni; Phone Number: +541148771070; Email: mjuni@fundaleu.org.ar

Study Locations

• Argentina
  • Ciudad Autonoma De Buenos Aires
    • Ciudad Autonoma de Buenos Aire, Ciudad Autonoma De Buenos Aires, Argentina, 1114
      • Recruiting
      • Fundaleu
      • Contact: Carolina Pavlovsky, MD; Phone Number: +541148771070; Email: cpavlovsky@fundaleu.org.ar
      • Contact: Mariana Juni; Phone Number: +541148771070; Email: mjuni@fundaleu.org.ar
      • Principal Investigator: Carolina Pavlovsky, MD
      • Sub-Investigator: Beatriz Moiraghi, MD
      • Sub-Investigator: Ana I Varela, MD
      • Sub-Investigator: Michele Bianchini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Signed Informed consent.
2. Patients with a diagnosis of CML BCR-ABL positive in CP treated with approved TKI (Imatinib, Nilotinib or Dasatinib) in 1st line or in 2nd line due to intolerance to the 1st line or in 2nd line due to the lack of deep MR with 1st line TKI, which never presented criteria for treatment failure.
3. Age ≥ 18 years
4. ≥ 4 years of treatment with imatinib, nilotinib or dasatinib.
5. Achievement of MR 4.5 in a standardized laboratory (BCR-ABL1 IS ≤ 0.0032%).
6. Evidence of MR 4.5 sustained for ≥ 2 years, as documented in at least 4 tests performed at least 3 months apart.
7. Evidence of typical quantifiable BCR-ABL1 transcript (b3a2 [e14a2] and / or b2a2 [e13a2], typical isoforms of p210).

Exclusion criteria:

1. Patients who previously discontinued TKI and demonstrated recurrence of the disease.
2. Patients with failure to any TKI at any time.
3. Patients who presented accelerated phase or CML in blast crisis at any time.
4. Patients with atypical transcript not quantifiable by RT qPCR
5. BCR-ABL mutation detected at any time during the course of the resistant disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: CML patient TKI discontinuation study; Treatment free remission in patients with chronic myeloid leukemia in chronic phase who achieved deep molecular response with tyrosine kinase inhibitors	Drug: Discontinuing treatment with Tyrosine Kinase Inhibitor after enrolment; Discontinuing treatment with Tyrosine Kinase Inhibitor after enrolment with a scheduled molecular monitoring until month 24.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular relapse free survival during 24 months	Molecular relapse free survival, defined as the time from the start of TKI interruption until the loss of the MMR. RQ PCR (IS) >0.1% BCR ABL will be considered as loss of MMR	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-free survival during 24 months	Treatment-free survival , defined as the time from the start of TKI interruption to the restart of the TKI.	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival during 24 months	Overall survival, defined from the day of TKI interruption until date of death, date of last contact or loss of follow-up.	24 months
Pharmacoeconomic analysis during 24 months	Calculate the total saving of the included patients un US dollars, considering the costs of TKIs, PCRs performing and medical visits,	24 months

Collaborators and Investigators

• Sponsor: Fundaleu

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): June 1, 2022
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: June 29, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: DISCONTINUATION
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Chronic Disease; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tyrosine Protein Kinase Inhibitors
• Other Study ID Numbers: Argentina Stop Trial; AST2018 (Other Identifier: FUNDALEU)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No