CALLS: CML and Ph+ALL Low Level Mutation Prevalence Survey

• ClinicalTrials.gov Identifier: NCT03647215
• Recruitment Status: Active, not recruiting
• First Posted: August 27, 2018
• Last Update Posted: April 8, 2021
• Sponsor: Incyte Biosciences UK
• Information provided by (Responsible Party): Incyte Corporation ( Incyte Biosciences UK )

Tracking Information

• First Submitted Date: August 23, 2018
• First Posted Date: August 27, 2018
• Last Update Posted Date: April 8, 2021
• Actual Study Start Date: December 18, 2017
• Actual Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 23, 2018)

• Percentage of participants with any mutation [ Time Frame: Up to approximately 1 month per individual participant. ]
  All samples will be processed by NGS.
• Frequency of all specific mutations [ Time Frame: Up to approximately 1 month per individual participant. ]
  All samples will be processed by NGS.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 23, 2018)

• Percentage of participants with individual mutations in chronic phase (CP)-CML, accelerated phase (AP)-CML, and blast phase (BP)-CML [ Time Frame: Up to approximately 1 month per individual participant. ]
  Participants in all phases of CML (CP, AP, and BP) will be enrolled.
• Frequency of individual mutations in chronic phase (CP)-CML, accelerated phase (AP)-CML, and blast phase (BP)-CML [ Time Frame: Up to approximately 1 month per individual participant. ]
  Participants in all phases of CML (CP, AP, and BP) will be enrolled.
• Percentage of participants with individual mutations in Ph+ ALL [ Time Frame: Up to approximately 1 month per individual participant. ]
  All samples will be processed by NGS.
• Frequency of individual mutations in Ph+ ALL [ Time Frame: Up to approximately 1 month per individual participant. ]
  All samples will be processed by NGS.
• Percentage of participants with individual mutations by whether a participant is intolerant or resistant to their previous TKI [ Time Frame: Up to approximately 1 month per individual participant. ]
  All samples will be processed by NGS.
• Frequency of individual mutations by whether a patient is intolerant or resistant to their previous TKI [ Time Frame: Up to approximately 1 month per individual participant. ]
  All samples will be processed by NGS.
• Percentage of participants with individual mutations by BCR-ABL level [ Time Frame: Up to approximately 1 month per individual participant. ]
  All samples will be processed by NGS. BCR-ABL levels defined as > 0.1% to 1% international scale (IS), > 1% to 10% IS, > 10% IS.
• Frequency of individual mutations by BCR-ABL level [ Time Frame: Up to approximately 1 month per individual participant. ]
  All samples will be processed by NGS. BCR-ABL levels defined as > 0.1% to 1% international scale (IS), > 1% to 10% IS, > 10% IS.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CALLS: CML and Ph+ALL Low Level Mutation Prevalence Survey
• Official Title: A Cohort Study To Establish the Prevalence of Mutations in Patients With CML Who Meet the ELN Criteria for Warning or Failure and Patients With Ph+ ALL With Detectable BCR-ABL Currently Being Treated With First or Subsequent TKI Therapy in the UK, Ireland, or France Using Next-Generation Sequencing
• Brief Summary: A multicenter, prospective cohort study of the mutation status of patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are being treated with first or subsequent tyrosine kinase inhibitor (TKI) therapy in the UK, Ireland, or France.
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample

Study Population

Approximately 50 centers in the UK, Ireland and France that treat adult patients with CML and Ph+ ALL will be selected for participation in the study. The sites selected will be a mixture of hospital and academic centers.

The target study population will include adult patients with CML who meet the ELN criteria for warning or failure or have high SOKAL score > 0.8 or presence of additional chromosomal abnormalities (ACAs), all with detectable BCR-ABL levels. Ph+ ALL patients must have detectable BCR-ABL levels. Patients will be taking their first or subsequent TKI.

Consecutive patients within each prescriber's practice who meet the enrollment criteria and provide informed consent will be invited to enroll into the study.

Repeat NGS KD mutation testing is permitted under the protocol as deemed part of the standard management of patients.

Condition

• Chronic Phase Chronic Myelogenous Leukemia
• Accelerated Phase Chronic Myelogenous Leukemia
• Blastic Phase Chronic Myelogenous Leukemia
• Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

• Intervention: Not Provided

Study Groups/Cohorts

All Participants

Participants with CML and Ph+ALL who are being treated with their first or subsequent TKI therapy. CML patients must meet the ELN criteria for warning and failure ) or have high SOKAL score (>0.8) or presence of additional chromosomal abnormalities (ACAs) and have detectable BCR-ABL levels. Ph+ALL patients need detectable BCR-ABL levels only.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: August 23, 2018): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2021
• Actual Primary Completion Date: March 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult patients (age ≥ 18 years) with CML (in all phases of disease) or Ph+ ALL with detectable BCR-ABL levels who are being treated with a first or subsequent TKI.

• Patients with CML must meet the warning or failure criteria as per the ELN guidelines for first second and subsequent treatment line, including:

  • BCR-ABL/ABL IS transcripts > 10% at 3 months
  • BCR-ABL/ABL IS transcripts > 1% at 6 months
  • BCR-ABL/ABL IS transcripts > 0.1% at 12 months or later
• Patients with CML must not currently be in MMR (ie, have disease with BCR-ABL1/ABL1 transcripts > 0.1% IS).

OR

• Patients with Ph+ ALL with any level of BCR-ABL/ABL IS transcripts. Patients with Ph+ ALL should have BCR-ABL1/ABL1 transcript levels > 0.1% and should not be currently enrolled in UKALL14 but may have relapsed during or after participation in UKALL14.
• Patients with an intermediate or high Sokal score (> 0.8) can be recruited into the study from 3 months after diagnosis, irrespective of BCR-ABL1/ABL1 transcript levels at 3 months.
• Patients with additional chromosomal abnormalities at diagnosis and patients with AP-CML may be recruited into the study, irrespective of BCR-ABL1/ABL1 transcript levels at 3 months and beyond provided BCR-ABL1/ABL1 transcript levels are > 0.1% IS. It is recommended that these patients have mutational analysis performed every 3 months irrespective of BCR-ABL1/ABL1 transcript levels until they reach MR3/MMR (BCR-ABL1/ABL1 < 0.1% IS).
• Any patients who have previously undergone testing for KD mutations, irrespective of KD mutational analysis test results.
• Patients who have the ability to understand the requirements of the study and provide written informed consent.

Exclusion Criteria:

Patients without detectable BCR-ABL and patients who have switched TKI due to intolerance but who have met the criteria for optimal response (CP-CML, ELN 2013 guidelines).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Ireland, United Kingdom

Administrative Information

• NCT Number: NCT03647215
• Other Study ID Numbers: INCB 84344-401
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: Blood samples will be identifiable by a code consisting of numbers and initials. Samples may be stored and tested for up to 5 years after the completion of the study.

• Responsible Party: Incyte Corporation ( Incyte Biosciences UK )
• Study Sponsor: Incyte Biosciences UK
• Collaborators: Not Provided

Investigators

• Study Director: Michael Thompson, MD; Incyte Biosciences UK

• PRS Account: Incyte Corporation
• Verification Date: April 2021