Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors

• ClinicalTrials.gov Identifier: NCT03610971
• Recruitment Status: Recruiting
• First Posted: August 1, 2018
• Last Update Posted: May 6, 2023
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: H. Jean Khoury Cure CML Consortium; Incyte Corporation
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Tracking Information

• First Submitted Date: July 19, 2018
• First Posted Date: August 1, 2018
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: November 19, 2019
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 26, 2018)

12 Month Treatment Free Remission (TFR) [ Time Frame: 12 months ]

TFR rate after completion of 12 cycles of combination therapy.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 26, 2018)

Adverse Events Possibly Related to Study Treatment [ Time Frame: Up to 30 days post treatment, approximately 13 months per participant ]

Establish the adverse event profile of ruxolitinib in combination with BCR-ABL TKIs: Adverse Events (AEs) and Serious Adverse Events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0, that are possibly, probably, or definitely related to study treatment.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: July 26, 2018)

Incidence of Improved Scores in Health Related Quality of Life Questionnaire [ Time Frame: Up to 48 months ]

Number of participants with an improved score in 2 or more categories of the questionnaire at the end of the TFR phase, when compared to the score for the same questions when completed at the end of 12 cycles of combination therapy.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors
• Official Title: Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors in Chronic Phase Chronic Myeloid Leukemia (CP-CML) Patients Who Relapsed After a Prior Attempt at TKI Discontinuation
• Brief Summary: The purpose of this study is to determine if adding Ruxolitinib to a Tyrone Kinase Inhibitor (TKI), prior to a second attempt at stopping a TKI will lead to prolonged treatment free remission (TFR).

Detailed Description

All participants will have a confirmed diagnosis of chronic phase chronic myeloid leukemia (CML) and must have previously attempted to discontinue TKI therapy. All participants must be restarted on a TKI at the time of relapse in order to be eligible for this trial.

After completion of 12 cycles of combination therapy, eligible participants will remain in the TFR phase of the study for up to 36 months, and will have central polymerase chain reaction (PCR) testing during the first 24 months. Therefore, the total duration of the trial will be approximately 48 months (12 months on combination treatment phase + 36 months in the TFR phase).

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Phase Chronic Myeloid Leukemia
• Chronic Myeloid Leukemia, Chronic Phase

Intervention

• Drug: Ruxolitinib
  Ruxolitinib: 15 mg by mouth (PO) twice a day (BID).
  Other Name: Jakafi®
• Drug: BCR-ABL Tyrosine Kinase Inhibitor (TKI)
  The BCR-ABL TKIs that will be used include imatinib, dasatinib, nilotinib or bosutinib.
  Other Name: TKI

Study Arms

Experimental: Combination Therapy + Remission Phase

Combination therapy followed by treatment free remission (TFR) phase.

Combination Therapy: Ruxolitinib plus BCR-ABL Tyrosine Kinase Inhibitors (TKIs).

All eligible patients will begin ruxolitinib in combination with their BCR-ABL TKI on cycle 1 day 1 of the combination phase. For cycle 2 and beyond, if day 1 of a cycle is delayed, day 1 procedures should be repeated if out of the specified window and day 1 of the cycle is considered the day study drug is restarted. They will continue combination therapy for a total of 12 cycles. Each cycle will be approximately 28 days.

At the end of 12 cycles ruxolitinib will be discontinued and any patient who has met the criteria for the treatment free remission (TFR) screening phase will enter into the TFR phase. Once in the TFR phase, participants will discontinue their BCR-ABL TKI and be monitored off treatment.

Interventions:

• Drug: Ruxolitinib
• Drug: BCR-ABL Tyrosine Kinase Inhibitor (TKI)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 4, 2022): 51
• Original Estimated Enrollment (submitted: July 26, 2018): 40
• Estimated Study Completion Date: January 2024
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Willing and able to give informed consent
• Diagnosed with CML in chronic phase and have either the b3a2 (e14a2) or b2a2 (e13a2) variants that give rise to the p210 BCR-ABL protein.
• Must have a documented history of attempting only one prior TKI discontinuation under the guidance of a treating physician

• Must have met ALL the following criteria prior to first attempt to discontinue their TKI:

  • Stable molecular response (MR4; <0.01% IS) for > 2 years, as documented on at least 4 tests, performed at least 3 months apart
  • Treatment with one of the following FDA approved TKI; imatinib, dasatinib, nilotinib or bosutinib, at any dose for a minimum of 3 years prior to discontinuing TKIs
  • Has been on any number of TKIs, but has not been resistant to any TKI (changes made for intolerance are allowed)
• Must have relapsed (defined as loss of major molecular response (MMR), RQ-PCR for BCR-ABL > 0.1% IS after first attempted discontinuation of TKI
• After first failed TFR attempt, must have a minimum duration of 1 year on a TKI, and must plan to remain on this same TKI for a minimum of 12 months during the combination treatment phase
• Current TKI must be the same as the TKI being taken prior to the initial TFR attempt (e.g., if patient is on imatinib prior to first TFR attempt, they should be on imatinib at time of enrollment on this study)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-3
• Must have a RQ-PCR for BCR-ABL less than 0.01% IS reported by the trial designated central lab at time of study enrollment
• Must adhere to all study contraception guidelines

Exclusion Criteria:

• History of accelerated or blast phase CML
• History of TKI resistance
• A second malignancy requiring active treatment
• Have previously received treatment with a JAK inhibitor.
• Platelet count less than 100 × 10^9/L or an absolute neutrophil count of less than 1 × 10^9/L or Hemoglobin less than 8 g/dL
• AST and ALT ≥ 3 times the institutional upper limit of normal (ULN)
• Creatinine ≥ 2 times ULN
• Total bilirubin ≥ 1.5 times ULN (unless direct bilirubin is within normal limits)
• Pregnant or lactating
• Unable to comply with lab appointments schedule and patient response outcome assessments
• Another investigational drug within 4 weeks of enrollment
• Any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with the completion of treatment according to this protocol
• Have undergone a prior allogeneic transplant
• Screening 12-lead ECG showing a baseline corrected QT interval >500msec (patients with a pacemaker will still be eligible with QTc>500msec)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03610971
• Other Study ID Numbers: MCC-19660; HJKC3-0002 ( Other Identifier: H. Jean Khoury Cure CML Consortium )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Original Study Sponsor: Same as current

Collaborators

• H. Jean Khoury Cure CML Consortium
• Incyte Corporation

Investigators

• Principal Investigator: Kendra Sweet, M.D.; H. Lee Moffitt Cancer Center and Research Institute

• PRS Account: H. Lee Moffitt Cancer Center and Research Institute
• Verification Date: May 2023