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

NCT03610971 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MCC-19660HJKC3-0002
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

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).

Conditions

Chronic Phase Chronic Myeloid Leukemia; Chronic Myeloid Leukemia, Chronic Phase

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 12 Month Treatment Free Remission (TFR)

  TFR rate after completion of 12 cycles of combination therapy.

  12 months post 12 cycles of treatment

Secondary Outcomes (1)

• Adverse Events Possibly Related to Study Treatment

  Up to 30 days post treatment, approximately 13 months per participant

Other Outcomes (1)

• Incidence of Improved Scores in Health Related Quality of Life Questionnaire

  Up to 48 months

Study Arms (1)

Combination Therapy + Remission Phase

EXPERIMENTAL

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; Drug: BCR-ABL Tyrosine Kinase Inhibitor (TKI)

Interventions

Ruxolitinib DRUG

Ruxolitinib: 15 mg by mouth (PO) twice a day (BID).

Also known as: Jakafi®

Combination Therapy + Remission Phase

BCR-ABL Tyrosine Kinase Inhibitor (TKI) DRUG

The BCR-ABL TKIs that will be used include imatinib, dasatinib, nilotinib or bosutinib.

Also known as: TKI

Combination Therapy + Remission Phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• H. Jean Khoury Cure CML Consortium: collaborator
• Incyte Corporation: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (8)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Emory -Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Memorial Sloan Kettering - Bergen

Montvale, New Jersey, 07645, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

David H. Koch Center for Cancer Care at Memorial Sloan Kettering

New York, New York, 10021, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Javier Pinilla-Ibarz, MD, PhD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2018
• First Posted: August 1, 2018
• Study Start: November 19, 2019
• Primary Completion: September 25, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

US (8)