Pacritinib With Aza for Upfront Myelodysplastic Syndrome

NCT07387354 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: iRIS ID- 2024-2998JT 36125
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will be conducted as a phase 1/2 study of safety and preliminary efficacy of pacritinib in combination with azacitidine for IPSS-M moderate low to very high risk MDS. Phase one will be a 3 + 3 design to assess the dose for the phase two portion. The phase two portion will employ a simon min-max two-stage design whereby fifteen patients will be enrolled in the first stage then ten more if at least two patients in stage one have a response. The dosing of pacritinib for the phase two study will be based on the phase one findings. Standard dosing of azacitidine will be used. A correlative study will be conducted in conjunction with the trial where the investigators will measure whole blood collected pre-treatment and at four days post-treatment to measure intracellular flow and phosflow to detect JAK/STAT, NF-κβ, and AKT/mTOR signaling in patient samples and how treatment affects these pathways.

Conditions

Myelodysplastic Syndromes; MDS; Myelodysplastic Syndrome, Unclassifiable; Hematologic Diseases; Bone Marrow Disease; Myeloproliferative Neoplasm

Keywords

Pacritinib; Azacitidine; IPSS-M; JAK/STAT; JAK/IRAK1; NF-κβ; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (3)

• Optimal Dose of Pacritinib in Combination with Azacitidine - Phase 1

  "Phase 1 of the study is designed to determine the optimal dose of pacritinib in combination with azacitidine in subjects with moderate, high, and very high risk MDS. The optimal dose (recommended Phase 2 dose, RP2D) will be defined as the highest dose level associated with an acceptable rate of dose-limiting toxicities (DLTs) during Cycle 1, using a standard 3 + 3 dose-escalation design. DLTs are defined per NCI CTCAE v5.0 (Section 7.5 of protocol): * Any grade ≥ 3 non-hematologic toxicity (excluding grade 3 nausea, vomiting, or diarrhea that improves to ≤ grade 2 within 5 days); * Prolonged grade 4 hematologic toxicities not due to persistent disease; * Any grade 5 toxicity not attributable to disease progression. Safety, tolerability, and pharmacodynamic data will support RP2D selection. "

  Baseline through Day 28 (Cycle 1)

• Rate of Dose Limiting Toxicities (DLTs) - Phase 1

  "the proportion of participants experiencing dose limiting toxicities (DLTs) occurring within thirty days of first dose of study agent that meets the following qualifications and is potentially related to study medication or combination will be considered a dose limiting toxicity. DLTs are defined per NCI CTCAE v5.0 as: * Any grade ≥ 3 non-hematologic toxicity (excluding grade 3 nausea, vomiting, or diarrhea that improves to ≤ grade 2 within 5 days); * Prolonged grade 4 hematologic toxicities (e.g., neutropenia or thrombocytopenia not due to persistent disease); * Any grade 5 toxicity not attributable to disease progression."

  Baseline through Day 28 (Cycle 1)

• Overall Response Rate (ORR) - Phase 2

  Overall response rate (ORR) = patients achieving CR (or CR equivalent), PR, CRL, CRh, or hematologic improvement (HI) ÷ total patients. ORR per IWG 2023 criteria; hematologic response per IWG 2018. Responses: CR, CR equivalent, PR, CRL, CRh, or HI (erythroid, platelet, neutrophil). IWG 2023: CR: BM \<5% blasts; Hb ≥10 g/dL; platelets ≥100×10⁹/L; ANC ≥1.0×10⁹/L; no blood blasts. CR equivalent: Baseline \<5% blasts + complete cytogenetic response. PR: CR criteria except ≥50% blast reduction (still ≥5%). CRL: \<5% blasts; no blood blasts; recovery of 1-2 lineages. CRh: \<5% blasts; no blood blasts; platelets \>50×10⁹/L; ANC \>0.5×10⁹/L. IWG 2018 HI: HI-E: Hb ↑ ≥1.5 g/dL or RBC TI ≥8 wks. HI-P: Platelets ↑ ≥30×10⁹/L or from \<20 to \>20×10⁹/L + ≥100% ↑. HI-N: ≥100% ↑ and absolute ↑ ≥0.5×10⁹/L.

  Baseline through Week 16 (approximately 4 months)

Secondary Outcomes (8)

• Duration of Overall Response Rate - Phase 2

  Up to 2 years after last patient enrolled

• Overall Surival - Phase 2

  Up to 24 months

• Number of Treatment Emergent Adverse Events (TEAEs)

  Baseline through Cycle 4, plus 30 days (Approximately 5 months)

• Molecular Response Rate (Phase 2)

  Baseline through Week 16 (approximately 4 months)

• Change in Intracellular Signaling Pathway Activation (JAK/STAT, NF-κB and AKT/mTOR

  Baseline

Study Arms (4)

Pacritinib 100 mg twice daily (200 mg total) - Dose level X-1 + azacitidine

EXPERIMENTAL

Participants will receive oral Pacritinib 100mg administered twice daily (200 mg total) in combination with Azacitidine 75mg/m² administered intravenously or subcutaneously on Days 1-7 of each 28-day cycle. The Phase 1 portion uses a 3+3 dose-escalation design to identify the recommended Phase 2 dose (RP2D)

Drug: Pacritinib; Drug: Azacitidine; Procedure: Bone Marrow Biopsy and Aspirate; Diagnostic Test: Laboratory Testing; Diagnostic Test: Electrocardiogram; Other: Quality of Life in Myelodysplasia Scale

Pacritinib 100 mg AM / 200 mg PM (300 mg total) - Dose level X (starting dose) + azacitidine

EXPERIMENTAL

Participants will receive oral Pacritinib administered twice daily in combination with Azacitidine administered intravenously or subcutaneously on Days 1-7 of each 28-day cycle. The Phase 1 portion uses a 3+3 dose-escalation design to identify the recommended Phase 2 dose (RP2D); the Phase 2 portion uses a Simon two-stage design to evaluate efficacy and safety at the RP2D.

Drug: Pacritinib; Drug: Azacitidine; Procedure: Bone Marrow Biopsy and Aspirate; Diagnostic Test: Laboratory Testing; Diagnostic Test: Electrocardiogram; Other: Quality of Life in Myelodysplasia Scale

Pacritinib 200 mg twice daily (400 mg total) - Dose level X+1 + azacitidine

EXPERIMENTAL

Participants will receive oral Pacritinib administered twice daily in combination with Azacitidine administered intravenously or subcutaneously on Days 1-7 of each 28-day cycle. The Phase 1 portion uses a 3+3 dose-escalation design to identify the recommended Phase 2 dose (RP2D); the Phase 2 portion uses a Simon two-stage design to evaluate efficacy and safety at the RP2D.

Drug: Pacritinib; Drug: Azacitidine; Procedure: Bone Marrow Biopsy and Aspirate; Diagnostic Test: Laboratory Testing; Diagnostic Test: Electrocardiogram; Other: Quality of Life in Myelodysplasia Scale

Pacritinib RP2D + azacitidine - Phase 2 Expansion

EXPERIMENTAL

Participants receive Pacritinib at the recommended Phase 2 dose (RP2D) as determined during the Phase 1 dose-escalation portion of the study, in combination with Azacitidine 75 mg/m2 intravenously or subcutaneously on Days 1-7 of each 28-day cycle.

Drug: Pacritinib; Drug: Azacitidine; Procedure: Bone Marrow Biopsy and Aspirate; Diagnostic Test: Laboratory Testing; Diagnostic Test: Electrocardiogram; Other: Quality of Life in Myelodysplasia Scale

Interventions

Pacritinib DRUG

Pacritinib is an oral kinase inhibitor with activity against wild-type JAK2, mutant JAK2V617F, FLT3, IRAK1, and ACVR1. Administered twice daily at 200mg or 400mg total daily dose per Phase 1 dose escalatio

Also known as: Vonjo

Pacritinib 100 mg AM / 200 mg PM (300 mg total) - Dose level X (starting dose) + azacitidine; Pacritinib 100 mg twice daily (200 mg total) - Dose level X-1 + azacitidine; Pacritinib 200 mg twice daily (400 mg total) - Dose level X+1 + azacitidine; Pacritinib RP2D + azacitidine - Phase 2 Expansion

Azacitidine DRUG

Lyophilized powder in 100mg single dose vials to be diluted in saline to generate 75 mg/m2 intravenous or subcutaneous solutions. Azacitidine to be given at 75mg/m2 infusion days 1-7 every four weeks.

Also known as: Vidaza, 5-Azacytidine

Pacritinib 100 mg AM / 200 mg PM (300 mg total) - Dose level X (starting dose) + azacitidine; Pacritinib 100 mg twice daily (200 mg total) - Dose level X-1 + azacitidine; Pacritinib 200 mg twice daily (400 mg total) - Dose level X+1 + azacitidine; Pacritinib RP2D + azacitidine - Phase 2 Expansion

Bone Marrow Biopsy and Aspirate PROCEDURE

Bone marrow aspiration and biopsy as per standard of care obtained at baseline, infusion visit Days 2-7, and study completion Day 112.

Also known as: BMA/BMB, Bone Marrow Examination, Bone Marrow Test

Pacritinib 100 mg AM / 200 mg PM (300 mg total) - Dose level X (starting dose) + azacitidine; Pacritinib 100 mg twice daily (200 mg total) - Dose level X-1 + azacitidine; Pacritinib 200 mg twice daily (400 mg total) - Dose level X+1 + azacitidine; Pacritinib RP2D + azacitidine - Phase 2 Expansion

Laboratory Testing DIAGNOSTIC_TEST

Laboratory Tests to include CMP, Magnesium Phosphorous, LDH, Uric Acid, and CBC with Differential will be performed at baseline, Cycle 1, and at the start of each subsequent cycle.

Also known as: CMP, Magnesium Phosphorous, LDH, Uric Acid

Pacritinib 100 mg AM / 200 mg PM (300 mg total) - Dose level X (starting dose) + azacitidine; Pacritinib 100 mg twice daily (200 mg total) - Dose level X-1 + azacitidine; Pacritinib 200 mg twice daily (400 mg total) - Dose level X+1 + azacitidine; Pacritinib RP2D + azacitidine - Phase 2 Expansion

Electrocardiogram DIAGNOSTIC_TEST

ECG will be obtained on day 7 of each cycle to document QTc interval. ECGs will be performed at clinician's discretion in addition to ones required by study as outlined above.

Also known as: ECG

Pacritinib 100 mg AM / 200 mg PM (300 mg total) - Dose level X (starting dose) + azacitidine; Pacritinib 100 mg twice daily (200 mg total) - Dose level X-1 + azacitidine; Pacritinib 200 mg twice daily (400 mg total) - Dose level X+1 + azacitidine; Pacritinib RP2D + azacitidine - Phase 2 Expansion

Quality of Life in Myelodysplasia Scale OTHER

Quality of life will be assessed using QUALMS at baseline and after completion of 4 cycles (Day 112). QUALMS is a 38-item assessment tool for patients with myelodysplastic syndromes (MDS).

Also known as: QUALMS

Pacritinib 100 mg AM / 200 mg PM (300 mg total) - Dose level X (starting dose) + azacitidine; Pacritinib 100 mg twice daily (200 mg total) - Dose level X-1 + azacitidine; Pacritinib 200 mg twice daily (400 mg total) - Dose level X+1 + azacitidine; Pacritinib RP2D + azacitidine - Phase 2 Expansion

Eligibility Criteria

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

You may qualify if:

• Patients must have histologic evidence of intermediate to high-risk myelodysplastic syndrome defined as having an IPSS-M score of moderate low, moderate high, high or very high risk. This will be assessed based on evaluations performed prior to screening for trial. Of note, the most recent evaluation pre-trial may be used which does not have to necessarily be at diagnosis.
• Subjects must have recovered from the toxic effects of any prior chemotherapy to ≤ Grade 1 (except alopecia).
• Required screening visit laboratory values: CrCL ≥45; total bilirubin \<2xULN except for patients with known Gilbert's disease; SGPT (ALT) ≤2xULN, PTT ≤1.5xULN.
• Negative pregnancy test for women with child-bearing potential at screening visit.
• Initial screening baseline QTc ≤480ms.
• Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
• Patients must have an absolute neutrophil count of ≥750 to enroll in study, this must be achieved without the addition of growth factor medication.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Any prior exposure to a hypomethylating agent (azacitidine or decitabine)
• Any prior exposure to JAK2 inhibitor therapy (ie ruxolitinib or prior pacritinib therapy)
• Any exposure within the past seven days of initiation of study treatment to a strong CYP3A inhibitor/inducer.
• Subjects must not be receiving any chemotherapy agents (except hydroxyurea) within the past thirty days.
• Subjects must not be receiving growth factors (erythropoietin mimetics, granulocyte stimulating factor mimetics, thrombopoietin mimetics) for two weeks prior to enrollment bone marrow. Subjects may not receive growth factors for the duration of this study.
• Subjects with a "currently active" second malignancy, other than curatively treated non-melanoma skin cancer, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pT2 with Gleason Score ≤ 6 and postoperative PSA \<0.5 ng/mL), or other adequately treated carcinoma-in-situ are eligible. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 1 year.
• Subjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure (NYHA class 2), myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligible.
• Bleeding event grade \>=2 (CTCAE 5.0) within prior three months unless provoked (e.g., by surgery or trauma)
• Use of anticoagulant or antiplatelet agents within fourteen days prior to day one with the exception of low dose aspirin (81mg daily).
• Subjects with other severe concurrent disease which in the judgment of the investigator would make the patient inappropriate for entry into this study are ineligible.
• Active or uncontrolled diarrhea or constipation.
• Subjects must not have evidence of active disease in the CNS.
• Subjects must not have received any investigational agents within fourteen days or five half-lives (whichever is longer) of study entry.
• Subjects must not be pregnant or breastfeeding. Pregnancy tests must be obtained for all females of child-bearing potential. Pregnant or lactating patients are ineligible for this study due to the unknown human fetal or teratogenic toxicities of pacritinib. Males or women of childbearing potential may not participate unless they have agreed to use a highly effective contraceptive method (defined in section 10.4.4).

Sponsors & Collaborators

• Thomas Jefferson University: lead
• CTI BioPharma: collaborator

MeSH Terms

Conditions

Myelodysplastic Syndromes; Hematologic Diseases; Bone Marrow Diseases; 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; Azacitidine; Bone Marrow Examination; Clinical Laboratory Techniques; Electrocardiography; Quality of Life

Condition Hierarchy (Ancestors)

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; Hematologic Tests; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Electrodiagnosis; Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health

Study Officials

• Chetan Jeurkar, DO

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chetan S Jeurkar, DO

CONTACT

215-955-8874; Chetan.Jeurkar@jefferson.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2026
• First Posted: February 4, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03