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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04626024
Recruitment Status : Recruiting
First Posted : November 12, 2020
Last Update Posted : January 12, 2021
Sponsor:
Information provided by (Responsible Party):
Martha Mims, Baylor College of Medicine

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.

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Chronic Myeloid Leukemia, BCR/ABL-Positive, in Remission Chronic Myeloid Leukemia in Remission Other: Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib Withdrawal Drug: Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib Re-initiation Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety And Efficacy Of Tyrosine Kinase Inhibitor Cessation For Chronic Myeloid Leukemia Patients With Stable Molecular Response In A Real World Population
Actual Study Start Date : December 22, 2020
Estimated Primary Completion Date : November 15, 2022
Estimated Study Completion Date : November 15, 2023


Arm Intervention/treatment
Experimental: All Subjects Enrolled (stop taking TKI)
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
Stop taking TKI medication

Drug: Imatinib Mesylate, Dasatinib, Nilotinib or Bosutinib Re-initiation
Re-start TKI medication
Other Names:
  • Gleevec
  • Sprycel
  • Tasigna
  • Bosulif




Primary Outcome Measures :
  1. Molecular relapse (MR) free survival [ Time Frame: From date of TKI cessation to the date of MR or censoring, assessed up to 6 months ]
    The Kaplan-Meier method will be used to estimate MR free survival rate at 6 months after TKI cessation with a 95% confidence interval.


Secondary Outcome Measures :
  1. ddPCR of BCR-ABL1 values affecting MR free survival [ Time Frame: At baseline (just before TKI cessation begins) ]
    ddPCR of BCR-ABL1 values (copies/μl) at baseline (just before TKI cessation begins) will be assessed by Cox proportional hazard regression model.

  2. Event free survival (EFS) [ Time Frame: From date of TKI cessation to the date of the event defined or censoring, assessed at 6 months and up to 24 months ]
    The event for EFS is defined as any of the following events: (i) loss of complete hematologic response (CHR), (ii) to accelerated phase or blast crisis (AP/BC), (iii) death due to any cause, whichever occurs first.The Kaplan-Meier method will be used to estimate EFS at 6months and up to 24 months after TKI cessation with a 95% confidence interval.

  3. Progression-free survival (PFS) [ Time Frame: From date of TKI cessation to the date of the progression defined or censoring, assessed at 6 months and up to 24 months ]
    The event of progression is defined by AP/BC or death due to any causes, whichever occurs first. The Kaplan-Meier method will be used to estimate PFS at 6 months and up to 24 months after TKI cessation with a 95% confidence interval.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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; patient cannot have had a known continuous interruption of TKI therapy of greater than 14 days or for a total of 6 weeks in the six months prior to registration.
  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), to be done after signed 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. 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).
  7. Any medical condition that, in the opinion of the investigator, would exclude the patient from participating in this study.
  8. Active liver disease (e.g., chronic active hepatitis, cirrhosis).
  9. Known diagnosis of human immunodeficiency virus (HIV) infection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04626024


Contacts
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Contact: Martha Mims, MD, PhD 713-798-7535 mmims@bcm.edu

Locations
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United States, Texas
Baylor College of Medicine- McNair Campus Recruiting
Houston, Texas, United States, 77030
Contact: Martha Mims, MD, PhD    713-798-7535    mmims@bcm.edu   
Ben Taub General Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Martha Mims, MD, PhD    713-798-7535    mmims@bcm.edu   
Contact: Carolyn Thibodeaux, BS    713-798-4797    carolynt@bcm.edu   
CHI St. Luke's Health Baylor College of Medicine Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: Martha Mims, MD, PhD    713-798-7535    mmims@bcm.edu   
Harris Health System- Smith Clinic Recruiting
Houston, Texas, United States, 77054
Contact: Martha Mims, MD, PhD    713-798-7535    mmims@bcm.edu   
Sponsors and Collaborators
Baylor College of Medicine
Investigators
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Principal Investigator: Martha P. Mims, MD, PhD Baylor College of Medicine
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Responsible Party: Martha Mims, Professor of Medicine; Section Chief, Hematology/Oncology, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT04626024    
Other Study ID Numbers: H-48054
First Posted: November 12, 2020    Key Record Dates
Last Update Posted: January 12, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Dasatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action