Clinical trial NCT03610971: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Phase Chronic Myeloid Leukemia
Chronic Myeloid Leukemia, Chronic Phase
Keywords: CP-CML
Chronic Myeloid Leukemia
CML
combination therapy
BCR-ABL oncogene
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: H. Jean Khoury Cure CML Consortium
name: Incyte Corporation
First posted: 2018-08-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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 (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)

Primary outcomes:
measure: 12 Month Treatment Free Remission (TFR)
timeFrame: 12 months
Secondary outcomes:
measure: Adverse Events Possibly Related to Study Treatment
timeFrame: Up to 30 days post treatment, approximately 13 months per participant
Other outcomes:
measure: Incidence of Improved Scores in Health Related Quality of Life Questionnaire
timeFrame: Up to 48 months
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory -Winship Cancer Institute
state: Georgia
city: Montvale
country: United States
facility: Memorial Sloan Kettering - Bergen
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: David H. Koch Center for Cancer Care at Memorial Sloan Kettering
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Milwaukee
country: United States
facility: Froedtert Hospital & the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Javier Pinilla-Ibarz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: