Pacritinib in CMML
ConditionChronic Myelomonocytic Leukemia
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorDouglas Tremblay
About this trial
This is a phase 1/2 trial of pacritinib in combination with azacitidine in patients with Chronic Myelomonocytic Leukemia (CMML). Patients will be newly diagnosed or previously treated but could not have received a prior JAK inhibitor. Patients who have previously been treated with a hypomethylating agent (HMA) must have received ≤ 1 cycle. Pacritinib will be initially tested at a dose of 200mg twice daily (dose level 0) in combination with azacitidine 75mg/m2, which can be administered subcutaneously or intravenously, for 7 days in a 28-day cycle. If there are 2 DLTs in the first 6 patients, there will be a dose escalation to pacritinib 100mg twice daily (dose level -1) and an additional 6 patients will be enrolled. Based on the phase 1, 3+3 dose de-escalation design, 6-12 patients will be enrolled in the phase 1 portion. After the completion of phase 1 and identification of the recommended phase 2 dose (RP2D), the trial will then proceed to phase 2 which will employ a Simon two stage design. This portion will include the 6 patients enrolled during the phase 1 portion at the MTD. An interim analysis for futility will occur. If 3 or fewer patients have had a clinical benefit (CB) or better, as defined by 2015 MDS/MPN IWG criteria, the PI and DSMC will meet to discuss the totality of the evidence and determine if the trial shall proceed. In the second stage, an additional 12 patients will be enrolled.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants must be ≥18 years of age at time of signing the Informed Consent Form (ICF).
Participants must voluntarily sign an ICF.
Participants must have a pathologically confirmed diagnosis of chronic myelomonocytic leukemia per World Health Organization (WHO) or International Consensus Classification (ICC)
Participants must be JAK inhibitor naïve.
Disqualifiers
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 2 weeks or within 5 half-lives of the prior investigational agent, whichever is shorter, of the first dose of treatment.
Active Graft Versus Host Disease (GVHD), or any GVHD requiring treatment with immunosuppression, with the exception of topical steroids and systemic steroids at a dose equivalent to prednisone 10mg or less and at a stable or decreasing dose. Any GVHD treatment (including calcineurin inhibitors) must be discontinued at least 28 days prior to Day 1 of study treatment.
Systemic treatment with a strong CYP3A4 inhibitor or a strong CYP450 inducer within 14 days prior to treatment Day 1 (see Appendix 13.7 and 13.8 for a list of CYP3A4 inhibitors and CYP450 inducers, respectively). Shorter washout periods may be permitted with approval of the Study Chair, provided that the washout period is at least five half-lives of the drug prior to treatment Day 1.
Other invasive malignancies within the last 3 years, except curatively treated non-melanoma skin cancer, localized prostate, cervical cancer, and any curatively treated carcinoma in situ.
Trial design
Design model
Sequential
Treatments tested in this trial
Pacritinib
DrugParticipants will take Pacritinib 100 mg - 200mg BID for each 28 day cycle
Azacitidine
DrugAzacitidine 75mg/m\^2 will be administered IV or SQ QD D1-7 of each 28 day cycle
Treatment groups
26 Participants
are divided into 1 treatment groupGroup A: Pacritinib in combination with AzacitidineExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Dose-limiting toxicity of Pacritinib in combination with Azacitidine
Phase 1: The recommended phase 2 dose (RP2D) for the combination of pacritinib with azacitidine will be determined based on the dose limiting toxicity (DLT) rate, defined as the proportion of participants in the DLT-evaluable population that experience a DLT within the first 4 weeks (1 cycle) of initiating treatment at the recommended phase 2 dose.
Time frame
at the end of one 28-day cycle2
Proportion of participants that achieve clinical benefit or better measured using 2015 MDS/MPN IWG Criteria
Phase 2: The preliminary efficacy of pacritinib in combination with azacitidine will be defined as the proportion of participants that achieve clinical benefit or better within 24 weeks (6 cycles, each cyce) of initiating treatment. Clinical benefit as defined by 2015 MDS/MPN IWG criteria within erythroid response, platelet response, neutrophil response, spleen response or symptom response.
Time frame
24 weeks (6 cycles, each cycle is 28 days)3
Overall Response Rate (ORR) to measure clinical benefit
Clinical benefit will be determined by evaluating overall response rate (ORR) which is defined by complete remission.
Time frame
24 weeks (6 cycles, each cycle is 28 days)Secondary outcomes
1
Number of Adverse events Grade 3 or higher measured using NCI CTCAE Version 5.0
Adverse experiences will be graded and recorded throughout the study and during the follow-up period according to NCI CTCAE Version 5.0. Toxicities will be characterized in terms regarding seriousness, causality, toxicity grading, and action taken with regard to trial treatment.
Time frame
up to 30 days after last study dose (up to 6 cycles, each cycle 28 days)2
Duration of Response (DOR) to measure efficacy
Preliminary efficacy of the combination of pacritinib with azacitidine as determined by duration of response (DOR). DOR is the length of time that a tumor continues to respond to treatment without the cancer growing or spreading.
Time frame
up to 24 months3
Overall Survival (OS) to measure efficacy
Preliminary efficacy of the combination of pacritinib with azacitidine as determined by duration of overall survival (OS). OS is defined as the time from the first dose of study treatment to the date of death (whatever the cause).
Time frame
up to 24 months4
Disease Free Survival (DFS) to measure efficacy
Preliminary efficacy of the combination of pacritinib with azacitidine as determined by disease free survival (DFS). DFS is defined as the time from randomization to recurrence of tumor or death.
Time frame
up to 24 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Douglas Tremblay
Lead sponsor
Icahn School of Medicine at Mount Sinai
Sponsor institution
Sobi, Inc.
Collaborator
Source ClinicalTrials.gov