Safety And Efficacy Of TKI Cessation For CML Patients With Stable Molecular Response In A Real World Population

NCT04626024 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: H-48054
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 4

Brief Summary

This is a single-arm, phase II study to evaluate safety and efficacy of tyrosine kinase inhibitor (TKI) cessation for chronic myeloid leukemia (CML) patients with stable molecular response in a real world population.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Molecular relapse (MR) free survival

  The Kaplan-Meier method will be used to estimate MR free survival rate at 6 months after TKI cessation with a 95% confidence interval.

  From date of TKI cessation to the date of MR or censoring, assessed up to 6 months

Secondary Outcomes (3)

• ddPCR of BCR-ABL1 values affecting MR free survival

  At baseline (just before TKI cessation begins)

• Event free survival (EFS)

  From date of TKI cessation to the date of the event defined or censoring, assessed at 6 months and up to 24 months

• Progression-free survival (PFS)

  From date of TKI cessation to the date of the progression defined or censoring, assessed at 6 months and up to 24 months

Study Arms (1)

All Subjects Enrolled (stop taking TKI)

EXPERIMENTAL

Patients with a diagnosis of Philadelphia chromosome- or BCR-ABL1-positive CML (as determined by cytogenetics, FISH, or PCR), prior evidence of a quantifiable BCR-ABL1 transcript by RT-PCR, and whom have been taking TKI for \> 36 months with a current status of complete molecular remission (CMR). TKI cessation begins within 7 days of study registration. Patients undergo BCR-ABL1 test every month in 24 months.

Other: Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib Withdrawal; Drug: Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib Re-initiation

Interventions

Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib Re-initiation DRUG

Re-start TKI medication

Also known as: Gleevec, Sprycel, Tasigna, Bosulif

All Subjects Enrolled (stop taking TKI)

Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib Withdrawal OTHER

Stop taking TKI medication

All Subjects Enrolled (stop taking TKI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are 18 years or older
• Patients have a diagnosis of Philadelphia chromosome- or BCR-ABL1-positive CML (as determined by cytogenetics, FISH, or PCR).
• Prior evidence of a quantifiable BCR-ABL1 transcript by RT-PCR
• Patients who have been taking TKI for \> 36 months.
• 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.
• 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.
• ECOG performance status \< 2
• 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
• Patients must not have any signs of extramedullary leukemia
• Patients must have a life expectancy of more than 12 months in the absence of any intervention
• All participants must be informed of the investigational nature of this study and must sign and give written informed consent
• Contraception requirements will be as per routine clinical practice.

You may not qualify if:

• Patients who are unable or unwilling to give their consent to participate to the study.
• Previous or planned allogeneic stem cell transplantation
• Patients who have pathologies or treatments that are able to enhance the potential relapse risk after stopping Imatinib.
• Patient has received an investigational agent within last 2 years
• Atypical BCR-ABL transcript not quantifiable by standard RQ-PCR.
• 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.
• Any medical condition that, in the opinion of the investigator, would exclude the patient from participating in this study.
• Active liver disease (e.g., chronic active hepatitis, cirrhosis).
• Known diagnosis of human immunodeficiency virus (HIV) infection.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (4)

Baylor College of Medicine- McNair Campus

Houston, Texas, 77030, United States

Location

Ben Taub General Hospital

Houston, Texas, 77030, United States

Location

CHI St. Luke's Health Baylor College of Medicine Medical Center

Houston, Texas, 77030, United States

Location

Harris Health System- Smith Clinic

Houston, Texas, 77054, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; Dasatinib; nilotinib; bosutinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Martha P. Mims, MD, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine; Section Chief, Hematology/Oncology

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: November 12, 2020
• Study Start: December 22, 2020
• Primary Completion (Estimated): November 15, 2028
• Study Completion (Estimated): November 15, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)