Trials / Not Yet Recruiting

Not Yet RecruitingNCT07387354

Pacritinib With Aza for Upfront Myelodysplastic Syndrome

A Phase 1/2 Study of Pacritinib in Combination With Azacitidine for the Treatment of IPSS-M Moderate Low to Very High Risk Myelodysplastic Syndrome

Status: Not Yet Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 25 (estimated)

Sponsor: Thomas Jefferson University · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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.

Detailed description

Phase I Design: Phase one will be a 3 + 3 design to assess the dose for the phase two portion. The investigators will use a two-stage accrual design at each dose considered. The investigators will initially enter three subjects at 300mg total. If none of the three experiences a dose-limiting toxicity (DLT) the investigators will proceed to 400mg total as our second dose. If one of the three experiences DLT, the investigators will enter three additional patients at 300mg total. If at most one experience DLT in the cohort of six at 300mg total, the investigators will proceed with 400mg total as our second dose. If two or more experience DLT in the cohort of six at 300mg total, the investigators will proceed to 200mg total as our second dose. If two or more experiences DLT in the original cohort of three at 300mg total, the investigators will proceed to 200mg total as our second dose. For the second dose (400mg or 200mg) three subjects will be initially treated. If none or one of the three experience a DLT, then the investigators will accrue three more subjects at that dose. If at most one of six experience a DLT, then the second dose will be given for phase two, called the highest tested dose if 400mg and highest tolerated dose if 200mg. If two or more of six experience a DLT on 400mg total, then the previous dose (300mg total) will be declared the highest tolerated dose. If two or more of six experience a DLT on 200mg total, then the investigators will terminate the trial. If there are two or more dose-limiting toxicities in the cohort of three on 400mg total, then the previous dose (300mg total) will be declared highest tolerated dose. If there are two or more dose-limiting toxicities in the cohort of three on 200mg total, then the investigators will terminate the trial. No patient will be treated at a higher dose until the three or six patients have completed their toxicity evaluation period at the current dose. With this plan, a dose with a 50% or greater probability of causing a dose-limiting toxicity has at most a 12.5% chance of satisfying the conditions for dose escalation after the first three subjects and at least a 50% chance of stopping at three. With the two-stages (3-6) together, there is at most a 17.2% chance of escalation. Phase II Design: Phase two of this trial is designed with the potential for early termination in the case of failure to prove efficacy. The design will be a Simon's two-stage admissible minimax design.40 Choice of design is guided by a desire to stop the trial early if the actual overall response rate (ORR) rate is 10% or less. If the ORR rate is 30% or greater, the investigators would like to have a low probability of failing to conclude effective. With this design, the investigators have no more than a 10% chance of concluding ineffective (≤10% ORR) when the ORR is at least 30%. Similarly, the investigators have no more than a 5% chance of concluding effective (≥30% ORR) when it is ineffective. If the actual ORR is 10% or lower, the investigators have 55% probability that the trial will stop after the first fifteen subjects. The first stage of fifteen patients will include the patients in the phase one portion who were on the chosen phase two dose. If there are greater than five successes after the total twenty-five patient cohort, then the trial is considered a success.

Conditions

Interventions

Type	Name	Description
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).

Timeline

Start date: 2026-05-01
Primary completion: 2027-01-01
Completion: 2027-01-01
First posted: 2026-02-04
Last updated: 2026-03-16

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT07387354. Inclusion in this directory is not an endorsement.