Stopping TKI treatment for stable chronic myeloid leukemia patients

Safety And Efficacy Of Tyrosine Kinase Inhibitor Cessation For Chronic Myeloid Leukemia Patients With Stable Molecular Response In A Real World Population

This study is testing if people with stable chronic myeloid leukemia can safely stop taking their TKI medication after being in remission for over three years.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Baylor College of Medicine (Academic / other)
• Drugs / interventions: Imatinib, dasatinib, nilotinib, bosutinib
• Locations: 4 sites (Houston, Texas and 3 other locations)
• Trial ID: NCT04626024 on ClinicalTrials.gov

What this trial studies

This phase II study evaluates the safety and efficacy of discontinuing tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML) who have maintained a stable molecular response. The study focuses on patients who have been on TKI therapy for over three years and have achieved a complete molecular remission. By assessing the outcomes of TKI cessation, the research aims to reduce the long-term side effects associated with prolonged TKI use while ensuring patient safety and maintaining remission status.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with Philadelphia chromosome-positive CML who have achieved stable molecular response for at least 24 months.

Not a fit: Patients who have not achieved a stable molecular response or have signs of extramedullary leukemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could allow patients to safely discontinue TKI therapy, reducing their exposure to long-term side effects.

How similar studies have performed: Other studies have explored TKI cessation in CML patients, showing promising results, but this specific approach in a real-world population is relatively novel.

Eligibility criteria

Inclusion Criteria

1. Patients who are 18 years or older
2. Patients have a diagnosis of Philadelphia chromosome- or BCR-ABL1-positive CML (as determined by cytogenetics, FISH, or PCR).
3. Prior evidence of a quantifiable BCR-ABL1 transcript by RT-PCR
4. Patients who have been taking TKI for \> 36 months.
5. Patients must have a history of stable molecular response, defined as MR4.5 for ≥24 months, as documented by ≥3 separate tests performed at least three months apart.
6. Patient must have a current status of complete molecular remission (CMR), defined as MR4.5 (per section 5.1), within 30 days of signing consent.
7. ECOG performance status \< 2
8. Patients must have normal marrow function within 30 days of registration, as defined:

   * Absolute Neutrophil Count (ANC) ≥ 1.5 x 10E9/L
   * Hemoglobin ≥ 9.0 g/dL
   * Platelets ≥ 100 x 10E9/L
9. Patients must not have any signs of extramedullary leukemia
10. Patients must have a life expectancy of more than 12 months in the absence of any intervention
11. All participants must be informed of the investigational nature of this study and must sign and give written informed consent
12. Contraception requirements will be as per routine clinical practice.

Exclusion Criteria

1. Patients who are unable or unwilling to give their consent to participate to the study.
2. Previous or planned allogeneic stem cell transplantation
3. Patients who have pathologies or treatments that are able to enhance the potential relapse risk after stopping Imatinib.
4. Patient has received an investigational agent within last 2 years
5. Atypical BCR-ABL transcript not quantifiable by standard RQ-PCR.
6. Patient cannot have had a known interruption of TKI therapy of greater than 14 consecutive days or for a total of 6 weeks in the six months prior to registration.
7. Another primary malignant disease, except those that do not currently require treatment (adequately treated conditions, such as excised skin cancer or cervical intra-epithelial neoplasia would not be considered exclusion criteria. If in doubt, please refer to the Principal Investigator).
8. Any medical condition that, in the opinion of the investigator, would exclude the patient from participating in this study.
9. Active liver disease (e.g., chronic active hepatitis, cirrhosis).
10. Known diagnosis of human immunodeficiency virus (HIV) infection.

Where this trial is running

Houston, Texas and 3 other locations

• Baylor College of Medicine- McNair Campus — Houston, Texas, United States (Recruiting)
• Ben Taub General Hospital — Houston, Texas, United States (Recruiting)
• CHI St. Luke's Health Baylor College of Medicine Medical Center — Houston, Texas, United States (Recruiting)
• Harris Health System- Smith Clinic — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Martha P. Mims, MD, PhD — Baylor College of Medicine
• Study coordinator: Martha Mims, MD, PhD

Conditions Chronic Myeloid Leukemia; Chronic Myeloid Leukemia, BCR/ABL-Positive, in Remission; Chronic Myeloid Leukemia in Remission