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Myelodysplastic SyndromesPhase 1/2MDSNCT07387354

Pacritinib With Aza for Upfront Myelodysplastic Syndrome

A Phase 1/2 study testing Pacritinib, Azacitidine and Bone Marrow Biopsy and Aspirate in people with Myelodysplastic Syndromes and MDS, run by Thomas Jefferson University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pacritinib, Azacitidine and Bone Marrow Biopsy and Aspirate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Sep 2026to Jan 2027
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Individuals must meet all of the following inclusion criteria to be eligible to participate in the study:
  • 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.

Who cannot join

  • 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.
Show all 19Show fewer
  • 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).
  • Subjects who have uncontrolled infection are not eligible. Patients must have any active infections under control. Fungal disease must be stable for at least two weeks before study entry.
  • Subjects with bacteremia must have documented negative blood cultures prior to study entry.
  • Subjects who are currently candidates for allogeneic transplantation, have a suitable donor, and are willing to undergo transplantation prior to study start.
  • Subjects who cannot hold a medication, over the counter, or supplemental product that in the investigator's opinion may put the patient at increased harm.

About this study

Official title: 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

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.

Read the 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.

Being tested
Pacritinib, Azacitidine, Bone Marrow Biopsy and Aspirate, Laboratory Testing, Electrocardiogram
Keywords
Pacritinib, Azacitidine, IPSS-M, JAK/STAT, JAK/IRAK1, NF-κβ, Myelodysplastic Syndrome
Medical subject headings
Myelodysplastic Syndromes, Hematologic Diseases, Bone Marrow Diseases, Myeloproliferative Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PacritinibDrug

    Also called Vonjo

    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

  • AzacitidineDrug

    Also called Vidaza, 5-Azacytidine

    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 AspirateProcedure or surgery

    Also called BMA/BMB, Bone Marrow Examination, Bone Marrow Test

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

  • Laboratory TestingDiagnostic test

    Also called CMP, Magnesium Phosphorous, LDH, Uric Acid

    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.

  • ElectrocardiogramDiagnostic test

    Also called ECG

    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 ScaleOther

    Also called QUALMS

    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 groups in NCT07387354
Study groupRoleWhat they receive
Pacritinib 100 mg twice daily (200 mg total) - Dose level X-1 + azacitidineExperimentalParticipants 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)
Receives: 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) + azacitidineExperimentalParticipants 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.
Receives: 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 + azacitidineExperimentalParticipants 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.
Receives: 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 ExpansionExperimentalParticipants 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.
Receives: Drug: Pacritinib; Drug: Azacitidine; Procedure: Bone Marrow Biopsy and Aspirate; Diagnostic Test: Laboratory Testing; Diagnostic Test: Electrocardiogram; Other: Quality of Life in Myelodysplasia Scale

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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. "

    Measured: Baseline through Day 28 (Cycle 1)

  2. 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."

    Measured: Baseline through Day 28 (Cycle 1)

  3. 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.

    Measured: Baseline through Week 16 (approximately 4 months)

Secondary outcomes (8)

  1. Duration of Overall Response Rate - Phase 2

    Time from first documented response (CR, PR, or HI per IWG criteria) until relapse, progression, or death from any cause.

    Measured: Up to 2 years after last patient enrolled

  2. Overall Surival - Phase 2

    Time from study enrollment to death from any cause.

    Measured: Up to 24 months

  3. Number of Treatment Emergent Adverse Events (TEAEs)

    Incidence, seriousness, severity, outcome, discontinuation or dose modifications related to TEAEs. This is separate from the primary endpoint of phase one which will be rate of DLTs.

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

  4. Molecular Response Rate (Phase 2)

    Assessment of molecular response will be done via rate of disappearance of relevant mutations via next-generation sequencing on pre and post treatment bone marrow samples.

    Measured: Baseline through Week 16 (approximately 4 months)

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

    Whole blood along with bone marrow aspirate with be collected pre and post treatment to assess intracellular flow and phosflow to detect NF-κB, JAK/STAT, and AKT/mTOR signaling within all myeloid cells. Post treatment will be compared to pre-treatment for all flow markers (intra- and extracellular) for changes in signaling and WBC maturation. Patient genetics will also be evaluated in the context of signaling response and maturation

    Measured: Baseline

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

    Whole blood along with bone marrow aspirate with be collected pre and post treatment to assess intracellular flow and phosflow to detect NF-κB, JAK/STAT, and AKT/mTOR signaling within all myeloid cells. Post treatment will be compared to pre-treatment for all flow markers (intra- and extracellular) for changes in signaling and WBC maturation. Patient genetics will also be evaluated in the context of signaling response and maturation

    Measured: After four days of azacitidine and pacritinib therapy

  7. Assessment of Quality of Life Using the quality of life in myelodysplasia scale (QUALMS)

    To measure quality of life pre-treatment and after four cycles of treatment using the quality of life in myelodysplasia scale (QUALMS). The Quality of Life in Myelodysplasia Scale (QUALMS) is a 38-item, disease-specific questionnaire used to measure the health-related quality of life in patients with myelodysplastic syndromes (MDS). It includes three subscales for physical burden, emotional burden, and benefit finding, and a total score ranges from 0 to 100, where a higher score indicates a better quality of life.

    Measured: At Baseline

  8. Assessment of Quality of Life Using the quality of life in myelodysplasia scale (QUALMS)

    To measure quality of life pre-treatment and after four cycles of treatment using the quality of life in myelodysplasia scale (QUALMS). The Quality of Life in Myelodysplasia Scale (QUALMS) is a 38-item, disease-specific questionnaire used to measure the health-related quality of life in patients with myelodysplastic syndromes (MDS). It includes three subscales for physical burden, emotional burden, and benefit finding, and a total score ranges from 0 to 100, where a higher score indicates a better quality of life.

    Measured: After 4 cycles of treatment (approximately 112 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2026
  2. Study startSep 2026 (estimated)
  3. Primary completionJan 2027 (estimated)
  4. Study completionJan 2027 (estimated)

Why it stopped: FDA requested significant changes to the study protocol

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07387354
Sponsor's protocol ID
iRIS ID- 2024-2998
Other IDs
JT 36125
Acronym
MDS
Status last verified
Aug 2026
First submitted
27 Jan 2026
Last updated
17 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pacritinib, Azacitidine and Bone Marrow Biopsy and Aspirate in people with Myelodysplastic Syndromes and MDS, run by Thomas Jefferson University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Optimal Dose of Pacritinib in Combination with Azacitidine - Phase 1 (time frame: Baseline through Day 28 (Cycle 1)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07387354.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.

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