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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Chronic Myeloid Leukemia, Chronic Phase; Chronic Phase Chronic Myeloid Leukemia
• Intervention / Treatment: Drug: Ruxolitinib; Drug: BCR-ABL Tyrosine Kinase Inhibitor (TKI)

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
• Enrollment (Estimated): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H. Lee Moffitt Cancer Center and Research Institute
      • Contact: Jhada-Kai Hunter; Phone Number: 813-745-0286; Email: Jhada-Kai.Hunter@moffitt.org
      • Contact: Javier Pinilla-Ibarz, MD, PhD; Phone Number: 813-745-4748; Email: Javier.Pinilla@moffitt.org
      • Principal Investigator: Javier Pinilla.Ibarz, MD, PhD
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Emory -Winship Cancer Institute
      • Contact: Rebecca Klisovic, MD; Phone Number: 404-778-1900; Email: Rebecca.Klisovic@emoryhealthcare.org
      • Principal Investigator: Rebecca Klisovic, MD
  • New Jersey
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering - Bergen
      • Contact: Michael Mauro, MD; Phone Number: 646-608-3744; Email: MauroM@mskcc.org
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Comprehensive Cancer Center
      • Contact: James Thompson, MD; Phone Number: 716-845-2300; Email: James.Thompson@roswellpark.org
      • Principal Investigator: James Thompson, MD
    • New York, New York, United States, 10021
      • Recruiting
      • David H. Koch Center for Cancer Care at Memorial Sloan Kettering
      • Contact: Michael Mauro, MD; Phone Number: 646-608-3744; Email: MauroM@mskcc.org
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Hospital
      • Contact: Quinna Lawson; Phone Number: 919-668-2556; Email: quinna.marshburn@duke.edu
      • Principal Investigator: Lindsey Rein, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Michael Heinrich, MD; Phone Number: 503-494-1080; Email: trials@ohsu.edu
  • Washington
    • Seattle, Washington, United States, 98109
      • Withdrawn
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital & the Medical College of Wisconsin
      • Contact: Ehab Atallah, MD; Phone Number: 414-805-4600; Email: eatallah@mcw.edu
      • Principal Investigator: Ehab Atallah, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 (allowance for a 2 week variance), as documented on at least 4 tests, performed at least 3 months apart. If any results are >0.05% IS, tests must have been repeated within 1 month and be less than 0.01% IS and stable.
  • Treatment with one of the following FDA approved TKI; imatinib, dasatinib, nilotinib or bosutinib, at any dose for a minimum of approximately 3 years (allowance of a 4 week variance) 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 0.0032% IS (MR4.5) 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 or >3.0 x the ULN with Gilbert Syndrome (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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Improved Scores in Health Related Quality of Life Questionnaire	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.	Up to 48 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Incyte Corporation; H. Jean Khoury Cure CML Consortium
• Investigators: Principal Investigator: Javier Pinilla-Ibarz, MD, PhD, H. Lee Moffitt Cancer Center and Research Institute

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2019
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: combination therapy; CP-CML; Chronic Myeloid Leukemia; CML; BCR-ABL oncogene
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chronic Disease; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors
• Other Study ID Numbers: MCC-19660; HJKC3-0002 (Other Identifier: H. Jean Khoury Cure CML Consortium)

Drug and device information, study documents

• 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