Clinical Trials /

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

NCT03610971

Description:

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).

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: MCC-19660
  • SECONDARY ID: HJKC3-0002
  • NCT ID: NCT03610971

Conditions

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

Interventions

DrugSynonymsArms
RuxolitinibJakafi®Combination Therapy + Remission Phase
BCR-ABL Tyrosine Kinase Inhibitor (TKI)TKICombination Therapy + Remission Phase

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Combination Therapy + Remission PhaseExperimentalCombination 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. They will continue combination therapy for a total of 12 cycles. Each cycle will be 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.
  • Ruxolitinib
  • BCR-ABL Tyrosine Kinase Inhibitor (TKI)

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 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:12 Month Treatment Free Remission (TFR)
Time Frame:12 months
Safety Issue:
Description:TFR rate after completion of 12 cycles of combination therapy.

Secondary Outcome Measures

Measure:Adverse Events Possibly Related to Study Treatment
Time Frame:Up to 30 days post treatment, approximately 13 months per participant
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • CP-CML
  • Chronic Myeloid Leukemia
  • CML
  • combination therapy
  • BCR-ABL oncogene

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