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

Chronic Myeloid Leukemia, Chronic Phase Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT03610971
• Other study ID #: MCC-19660
• Secondary ID: HJKC3-0002
• Status: Recruiting
• Phase: Phase 2
• Start date: November 19, 2019
• Est. completion date: January 2025

Study information

• Verified date: May 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 51
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
United States	Emory -Winship Cancer Institute	Atlanta	Georgia
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Duke University Hospital	Durham	North Carolina
United States	Froedtert Hospital & the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering - Bergen	Montvale	New Jersey
United States	David H. Koch Center for Cancer Care at Memorial Sloan Kettering	New York	New York
United States	Oregon Health & Science University	Portland	Oregon
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (3)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	H. Jean Khoury Cure CML Consortium, Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	12 Month Treatment Free Remission (TFR)	TFR rate after completion of 12 cycles of combination therapy.	12 months
Secondary	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

External Links

•   Moffitt Cancer Center Clinical Trials website