Pacritinib With Aza for Upfront Myelodysplastic Syndrome

Sponsor
Thomas Jefferson University
Study ID
NCT07387354
Phase
PHASE1/PHASE2
Status
Not Yet Recruiting

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Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).

Study Details

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.

Key Dates

Start date
Jul 31, 2026
Status verified
Jun 2026
Primary completion
Jan 31, 2027
Completion
Jan 31, 2027

Study Design

Enrollment
25 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

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

Primary Outcome Measure

Optimal Dose of Pacritinib in Combination with Azacitidine - Phase 1 [ Time Frame: Baseline through Day 28 (Cycle 1) ]

Central Contacts

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