Pacritinib With Aza for Upfront Myelodysplastic Syndrome

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

Interventions

DRUG

Pacritinib

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

DRUG

Azacitidine

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.

PROCEDURE

Bone Marrow Biopsy and Aspirate

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

DIAGNOSTIC_TEST

Laboratory Testing

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.

DIAGNOSTIC_TEST

Electrocardiogram

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.

OTHER

Quality of Life in Myelodysplasia Scale

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).

Sponsors & Collaborators

• CTI BioPharma

  collaborator INDUSTRY

• Thomas Jefferson University

  lead OTHER

Principal Investigators

• Chetan Jeurkar, DO · Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-31

Primary Completion

2027-01-31

Completion

2027-01-31

FDA Drug

Yes