Phase I Trial of Pacritinib in Combination With Venetoclax and Azacitidine for the Treatment of Accelerated and Blast Phase Myeloproliferative Neoplasms

NCT07679334 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: I-3685225
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of pacritinib when given together with venetoclax and azacitidine in treating patients with accelerated and blast phase myeloproliferative neoplasms (MPN-AP/BP). Pacritinib and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving pacritinib together with venetoclax and azacitidine may be safe, tolerable, and/or effective in treating patients with MPN-AP/BP

Conditions

Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose (MTD) of the treatment regimen.

  WIll be measured by assessing DLTS in a Bayesian optimal interval )BOIN design to determine the MTD

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (12)

• Incidence of adverse events (AEs)

  Up to 30 days post treatment

• Percentage of Complete Response

  24 months

• Complete response with incomplete hematologic recovery rate

  Up to 1 year post start of treatment

• Complete response with partial hematologic recovery rate

  UP to 1 year post start of treatment

• Complete Response without evidence of measurable residual disease rate

  UP to 1 year post start of treatment

Study Arms (1)

Treatment Arm 1

EXPERIMENTAL

Pacritinib in combination with venetoclax and azacitidne. Dose will increase until side effects occur or maximum tolerated dose is reached. Additionally, patients undergo MRI or CT as well as bone marrow aspiration and biopsy throughout the trial.

Drug: Pacritinib; Drug: Venetoclax; Drug: Azacitidine; Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Procedure: Bone Marrow Aspiration

Interventions

Pacritinib DRUG

Subjects will be dosed until MTD is reached

Also known as: 937272-79-2, SB-1518

Treatment Arm 1

Venetoclax DRUG

Given PO

Also known as: 1257044-40-8

Treatment Arm 1

Azacitidine DRUG

Given SC or IV

Also known as: 320-67-2

Treatment Arm 1

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI

Treatment Arm 1

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT Scan

Treatment Arm 1

Bone Marrow Aspiration PROCEDURE

Undergo bone marrrow aspiration

Treatment Arm 1

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Subjects with blast phase MPN must be newly diagnosed/untreated (no prior blast reduction therapy for blast phase disease except for hydroxyurea and/or a JAK inhibitor; treatment of a prior accelerated phase is allowed). Prior treatment with a hypomethylating agent (with or without a JAK inhibitor) is allowed for accelerated phase MPN. Prior treatment with any JAK inhibitor (including pacritinib) is allowed for any phase of disease (chronic, accelerated, or blast); however, must not have discontinued pacritinib due to toxicity. If a participant previously required dose reduction during pacritinib therapy and tolerated it well, then may enroll into a cohort utilizing that dose level or lower.
• WBC \< 25 x 109/L prior to treatment initiation- subjects with WBC ≥ 25 x 109/L may still be eligible after receiving cytoreduction measures such as hydroxyurea and/or leukapheresis if WBC becomes \< 25 x 109/L prior to treatment initiation. Cytoreduction with hydroxyurea and/or leukapheresis is allowed prior to treatment. Hydroxyurea must be discontinued ≥ 12 hours prior to treatment initiation.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration:
• Total bilirubin: ≤ 1.5 x upper limit of normal (ULN) unless considered to be due to Gilbert's Syndrome, hemolysis, or leukemic organ involvement. Total bilirubin WBC \< 25 x 109/L prior to treatment initiation- subjects with WBC ≥ 25 x 109/L may still be eligible after receiving cytoreduction measures such as hydroxyurea and/or leukapheresis if WBC becomes \< 25 x 109/L prior to treatment initiation. Cytoreduction with hydroxyurea and/or leukapheresis is allowed prior to treatment. Hydroxyurea must be discontinued ≥ 12 hours prior to treatment initiation.
• Demonstrate adequate organ function as defined below. All screening labs to be obtained within 28 days prior to registration:
• Total bilirubin: ≤ 1.5 x upper limit of normal (ULN) unless considered to be due to Gilbert's Syndrome, hemolysis, or leukemic organ involvement. Total bilirubin must be \< 3 x upper limit normal in subjects with Gilbert's Syndrome, hemolysis, or leukemic organ involvement.
• Aspartate aminotransferase (AST): ≤ 3 x ULN (≤ 5 x ULN if considered to be due to myelofibrosis or leukemic organ involvement).
• Alanine aminotransferase (ALT): ≤ 3 x ULN (≤ 5 x ULN if considered to be due to myelofibrosis or leukemic organ involvement).
• Creatinine clearance: ≥ 30 mL/min by Cockcroft-gault formula or measured by 24-hour urine collection.
• Participants of child-bearing potential must agree to use highly effective contraceptive methods prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• Diagnosis of de novo AML, acute promyelocytic leukemia, or accelerated or blast phase MPN without a documented prior diagnosis of ET, PV, or PMF.
• Known CNS leukemia involvement. NOTE: Subjects with clinical suspicion or signs of neurologic deficit should undergo a screening lumbar puncture prior to enrollment to confirm lack of CNS leukemia.
• Previous treatment with BCL-2/BCL-X inhibitors (including venetoclax and navitoclax).
• Prior allogeneic stem cell transplantation for blast phase disease. Prior allogeneic stem cell transplantation for chronic and accelerated phase MPN is allowed. Subjects must not have received transplant within 60 days. Cannot be receiving immunosuppression therapy, with the exception of prednisone ≤10mg/d (or equivalent), for the treatment or prophylaxis of GVHD. If the subject has been on immunosuppressant treatment or prophylaxis for GVHD, the treatment must have been discontinued at least 14 days prior to study treatment and there must be no evidence of Grade ≥ 2 GVHD.
• Treatment with moderate or strong CYP3A4 inhibitors or strong CYP3A4 inducers within five half-lives or 14 days, whichever is shorter, prior to the initiation of study treatment.
• Treatment with chemotherapy, wide-field radiation, or biologic therapy, with the exception of hydroxyurea as above, and all trans-retinoic acid given initially for presumed APML, within 14 days of study entry. Prior JAK inhibitor (other than pacritinib) must be held for five half-lives prior to study entry. Administration of steroids to prevent withdrawal symptoms is allowed.
• Treatment with investigational drug within five half-lives or 14 days, whichever is shorter, prior to study entry.
• Baseline prolonged QTc of \> 480 msec. QTc measured by Fridericia's formula (QTc=QT/\[RR1/3\]) based on the mean of triplicate reads. Repeat EKGs after correction of electrolytes or discontinuation of QT prolonging medications are allowed to meet entry criteria.
• Grade ≥2 bleeding event within the previous 3 months. Treatment with anticoagulation or antiplatelet agents (except for aspirin at dosages ≤100 mg per day or prophylactic doses of enoxaparin or heparin) within five half-lives or 7 days, whichever is shorter.
• Any GI or metabolic condition that could interfere with absorption of oral medication.
• Known severe (Child-Turcotte-Pugh class C) hepatic cirrhosis. Testing not required.
• Pre-existing uncontrolled pathology such as heart failure (congestive/ischemic, NYHA classes III and IV), clinically significant abnormalities on a 12-lead electrocardiogram, significant pulmonary disease, severe/unstable arrhythmias/angina pectoris/hypertension, acute or chronic pancreatitis, etc. Acute myocardial infarction or stroke within 6 months of study entry.
• Known active HIV, Hepatitis B, or Hepatitis C infection; testing not required.
• Active uncontrolled or severe systemic infection. Enrollment is possible after control of infection, at discretion of the treating physician.
• History of another active malignancy in the previous 2 years, with the exception of:

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; venetoclax; Azacitidine; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Steven Green, MD

  Roswell Park Comprehensive Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ASK ROSWELL

CONTACT

1-800-767-9355; AskRoswell@roswellpark.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2026
• First Posted: July 1, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: July 31, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)