Recruiting
Phase 1
Phase 2

Pacritinib

Sponsor:

Douglas Tremblay

Code:

NCT06159491

Conditions

Chronic Myelomonocytic Leukemia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pacritinib

Azacitidine

Study Details

Brief summary:

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.

Conditions

Chronic Myelomonocytic Leukemia

Study ID

NCT06159491

Start date

Sep 18, 2024

Status verified date

Aug, 2026

Completion date

Jan, 2028

Anticipated

Primary completion date

Jul, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.
  • Participants may be hypomethylating agent (HMA) naïve or can be treated with up to one prior cycle.
  • Participants must have either proliferative CMML (WBC ≥13 x 109/L) or have intermediate-2 or high risk CMML by the clinical/molecular CMML-specific prognostic scoring system (CPSS-Mol).
  • Participants must have a life expectancy of at least 24 weeks per investigator.
  • ECOG performance status ≤ 3.
  • Females of reproductive potential should use effective contraception during treatment with azacitidine and for 6 months after the last dose and males with female partners of reproductive potential should use effective contraception during treatment with azacitidine and for 3 months after the last dose.
  • Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy.
  • Must have adequate organ function as demonstrated by the following:

  • Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) unless considered due to leukemic organ involvement, Gilbert's syndrome, or hemolysis.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN.
  • Creatinine clearance (CrCl) of ≥30 mL/min.
  • PT or INR <=1.5x ULN and PTT or aPTT <=1.5x ULN.
  • ANC >= 500 cells/μL.
  • Ability to adhere to the study visit schedule and all protocol requirements.
  • Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

  • 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.
  • Presence of active serious infection.

  • If a patient is identified to have COVID-19 during the screening period, participants may be considered eligible if in the opinion of the investigator there are no COVID-19 sequlae that may place the patient at a higher risk of receiving investigational treatment.
  • Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the patient from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Known history of uncontrolled human immunodeficiency virus (HIV).
  • Significant recent bleeding history defined as NCI CTCAE grade ≥2 within 3 months prior to treatment Day 1, unless precipitated by an inciting event (e.g., surgery, trauma, or injury).
  • Systemic treatment with medications that increase the risk of bleeding, including anticoagulants, antiplatelet agents (except for aspirin dosages of ≤100 mg per day), anti-vascular endothelial growth factor (anti-VEGF) agents, and daily use of COX-1 inhibiting Non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to treatment Day 1.
  • Any history of CTCAE grade ≥2 cardiac conditions within 6 months prior to treatment Day 1. Patients with asymptomatic grade 2 non-dysrhythmia cardiovascular conditions may be considered for inclusion, with the approval of the Study Chair, if stable and unlikely to affect patient safety.
  • Heart failure other than NYHA class I (asymptomatic, without limitation).
  • QT corrected by the Fridericia method (QTcF) prolongation >480 ms or other factors that increase the risk for QT interval prolongation (e.g., hypokalemia \[defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction\], or history of long QT interval syndrome).
  • Known active systemic hepatitis B, or C infection requiring therapy or known cirrhosis.
  • Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or pharmaceutical sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific participant.
  • Organ transplant recipients other than bone marrow transplant.
  • Women who are pregnant or lactating.
  • Patient with known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of pacritinib, including difficulty swallowing, are not eligible.

Study Design

Enrollment

26 participants

Anticipated

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Pacritinib in combination with Azacitidine

Participants will take pacritinib 200 mg BID for each 28 day cycle, azacitidine 75mg/m2 will be administered IV or SQ QD D1-7 of each 28 day cycle

Interventions

Pacritinib

Participants will take Pacritinib 100 mg - 200mg BID for each 28 day cycle

Azacitidine

Azacitidine 75mg/m\^2 will be administered IV or SQ QD D1-7 of each 28 day cycle

Primary outcome measure

  • Dose-limiting toxicity of Pacritinib in combination with Azacitidine [ Time Frame: at the end of one 28-day cycle ]
  • Proportion of participants that achieve clinical benefit or better measured using 2015 MDS/MPN IWG Criteria [ Time Frame: 24 weeks (6 cycles, each cycle is 28 days) ]
  • Overall Response Rate (ORR) to measure clinical benefit [ Time Frame: 24 weeks (6 cycles, each cycle is 28 days) ]

Central Contacts and Locations

Central contacts

Gabriela Bello

212-243-0463gabriela.bello@mssm.edu

Katherine Vandris

katherine.vandris@mssm.edu

Locations

The Mount Sinai Hospital

Recruiting

New York, New York, United States, 10029

Contacts

Gabriela Bello

gabriela.bello@mssm.edu

Katherine Vandris

917-841-2454katherine.vandris@mssm.edu

Principal Investigator:

Douglas Tremblay

More Information

Sponsor

Douglas Tremblay

Last update posted

Aug 11, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Douglas Tremblay on 2026-08-11.