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Graft Vs Host DiseasePhase 1/2NCT02891603

A Phase I/II GVHD Prevention Trial Combining Pacritinib With Sirolimus-Based Immune Suppression

A Phase 1/2 study testing Pacritinib, Sirolimus and Tacrolimus in people with Graft Vs Host Disease and GVHD, run by H. Lee Moffitt Cancer Center and Research Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to examine a new approach to preventing a serious problem after transplant called graft vs. host disease (abbreviated as GVHD). This is a 3 arm sequential phase I/II, study of Pacritinib with Sirolimus and Tacrolimus (PAC/SIR/TAC) for the prevention of acute GVHD after matched related and… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft Vs Host Disease, GVHD
What is being tested?
Pacritinib, Sirolimus and Tacrolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesUnited States
Study dates
8 Jun 2017to 18 Apr 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Must have an available 8/8 HLA-A, -B, -C, and -DRB1 matched-related or unrelated donor allogeneic hematopoietic peripheral blood stem cell graft.
  • Signed informed consent.
  • Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, myeloproliferative neoplasms, Hodgkin lymphoma, or non-Hodgkin lymphoma requiring a matched allogeneic hematopoietic stem cell transplantation (HSCT). Acute Leukemia (AML or ALL) must be in complete remission defined as: <5% marrow blasts with no morphologic evidence of leukemia, no peripheral blasts, marrow >20% cellular, and peripheral absolute neutrophil count >1000/uL (platelet recovery is not required). Myelodysplasia (MDS) and chronic myeloid leukemia (CML): Must have <5% marrow blasts. Myeloproliferative neoplasms (MPN): Must have <5% peripheral / marrow blasts. Note: Prior use of a JAK2 inhibitor is allowed up to 4 weeks before day 0 of alloHCT. Hodgkin and non-Hodgkin lymphoma: Must have chemosensitive disease.
  • Adequate vital organ function.
  • Performance status: Karnofsky Performance Status Score ≥ 80%.
  • Donor Eligibility:
  • Eligible donors will include healthy sibling, relative or unrelated donors that are matched with the patient at HLA-A, B, C, and DRB1 by high resolution typing as defined by the Collaborative Trials Network.

Who cannot join

  • Active infection not controlled with appropriate antimicrobial therapy.
  • History of HIV, hepatitis B, or active hepatitis C infection.
  • Anti-thymocyte globulin, alemtuzumab, bortezomib, or post-transplant cyclophosphamide as part of GVHD prophylaxis.
  • Sorror's co-morbidity factors with total score >4.
  • Any patient anticipating or scheduled to receive a tyrosine kinase inhibitor, FLT3 inhibitor, or JAK2 inhibitor (outside of this study) post-HCT.
  • QTc>450ms per Fridericia's correction.
Show all 12Show fewer
  • Thrombin time (TT), prothrombin time (PT), or partial thromboplastin time (PTT) >2x upper limit of normal (ULN).
  • Grade 3 or higher recent (within the past 6 months) or ongoing non-QTc cardiac adverse events/comorbidities.
  • Grade 3 or higher recent or ongoing cardiac dysrhythmias, family history of long QT.
  • syndrome, or serum potassium <3.0 mEq/L that is persistent and refractory to correction.
  • Grade 3 or higher recent or ongoing bleeding events.
  • Symptomatic or uncontrolled cardiovascular disease, myocardial infarction or severe/unstable angina within the past 6 months, or New York Heart Association (NYHA) Class III or IV congestive heart failure.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

The purpose of this study is to examine a new approach to preventing a serious problem after transplant called graft vs. host disease (abbreviated as GVHD).

This is a 3 arm sequential phase I/II, study of Pacritinib with Sirolimus and Tacrolimus (PAC/SIR/TAC) for the prevention of acute GVHD after matched related and unrelated allogeneic hematopoietic cell transplantation (alloHCT).

Read the detailed description

GVHD is a common problem that occurs after transplant despite the use of standard immune suppressive medications (these are called sirolimus and tacrolimus). GVHD can result in skin rash, nausea, vomiting, diarrhea, and liver damage. Severe GVHD can be life-threatening.

In this study, investigators will add a medication called pacritinib to the combination of sirolimus and tacrolimus to see if this approach can more effectively prevent GVHD. Pacritinib is a medicine used to treat a disease of the bone marrow called myelofibrosis Pacritinib turns off a switch in cells called Janus Kinase 2 (JAK2). Pacritinib is an investigational medicine used in several clinical trials and not FDA approved. JAK2 is an important regulator of inflammation. This inflammation is thought to contribute to GVHD. Pacritinib is able to turn this inflammation off by inhibiting JAK2. Research has shown that blocking JAK2 prevents GVHD in mice and also reduces severe GVHD in transplant patients. Doctors at Moffitt have identified that inflammation from JAK2 is an important cause of GVHD, and is present well before patients develop GVHD symptoms. This trial will study how well pacritinib turns off inflammation during the transplant and if it prevents GVHD when added to our standard medicines.

Pacritinib will begin the day of the participant's transplant (Day 0) and will continue until 70 days after the transplant.

Sirolimus will be given the day before transplant and continued daily for at least one year.

Tacrolimus will begin 3 days before transplant and will be given for at least 50 days.

Being tested
Pacritinib, Sirolimus, Tacrolimus, Allogenic hematopoietic cell transplant (alloHCT)
Medical subject headings
Graft vs Host Disease

What participants receive

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

  • PacritinibDrug

    Also called PAC, tyrosine kinase inhibitor (TKI)

    Pacritinib Dose and Schedule: 200 mg twice a day (BID) orally from day 0 until day +100. PAC will be tapered to 50% of the total dose at day +70, then 25% of total dose at day +84, then stop at day +100 (+/- 7 days).

  • SirolimusDrug

    Also called Rapamune

    Sirolimus (SIR) will be administered and dosed according to Moffitt Cancer Center, Department of Blood and Marrow Transplantation standard practice. Attending physician discretion is permitted with regard to timing, rapidity, and completion of SIR taper. SIR levels will be monitored according to program standard operating procedures. Dose modifications of SIR for concurrent use of CYP3A4 inhibitors or inducers will be based on program standard operating procedures.

  • TacrolimusDrug

    Also called Prograf

    Tacrolimus (TAC) will be administered and dosed according to Moffitt Cancer Center, Department of Blood and Marrow Transplantation standard practice. Attending physician discretion is permitted with regard to timing, rapidity, and completion of TAC taper. TAC levels will be monitored according to program standard operating procedures. Dose modifications of TAC for concurrent use of CYP3A4 inhibitors or inducers will be based on program standard operating procedures.

  • Allogenic hematopoietic cell transplant (alloHCT)Procedure or surgery

    Patients will undergo allogenic hematopoietic cell transplant (alloHCT) as a part of their standard of care treatment.

Study groups in NCT02891603
Study groupRoleWhat they receive
Phase 1, Level 1: Pacritinib with Sirolimus and TacrolimusExperimentalAfter standard of care allogenic hematopoietic cell transplantation, Pacritinib will be added to standard treatment with Sirolimus and Tacrolimus (PAC/SIR/TAC). 100 mg Pacritinib will begin taken by mouth the day of the participant's transplant (Day 0) and will continue until 70 days after the transplant.. Sirolimus will be given the day before transplant and continued daily for at least one year. Tacrolimus will begin 3 days before transplant and will be given for at least 50 days.
Receives: Drug: Pacritinib; Drug: Sirolimus; Drug: Tacrolimus; Procedure: Allogenic hematopoietic cell transplant (alloHCT)
Phase 1, Level 2: Pacritinib with Sirolimus and TacrolimusExperimentalAfter standard of care allogenic hematopoietic cell transplantation, Pacritinib will be added to standard treatment with Sirolimus and Tacrolimus (PAC/SIR/TAC). 100 mg Pacritinib will begin taken by mouth twice daily starting the day of the participant's transplant (Day 0) and continuing until 70 days after the transplant.. Sirolimus will be given the day before transplant and continued daily for at least one year. Tacrolimus will begin 3 days before transplant and will be given for at least 50 days.
Receives: Drug: Pacritinib; Drug: Sirolimus; Drug: Tacrolimus; Procedure: Allogenic hematopoietic cell transplant (alloHCT)
Phase 2: Pacritinib with Sirolimus and TacrolimusExperimentalAfter standard of care allogenic hematopoietic cell transplantation, Pacritinib will be added to standard treatment with Sirolimus and Tacrolimus (PAC/SIR/TAC). Patients will take Pacritinib at the MTD: 100 mg Pacritinib will begin taken by mouth twice daily starting the day of the participant's transplant (Day 0) and continuing until 70 days after the transplant.. Sirolimus will be given the day before transplant and continued daily for at least one year. Tacrolimus will begin 3 days before transplant and will be given for at least 50 days.
Receives: Drug: Pacritinib; Drug: Sirolimus; Drug: Tacrolimus; Procedure: Allogenic hematopoietic cell transplant (alloHCT)

What is being measured

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

  1. STAT Activity

    STAT3 activity in circulating CD4+ T-cells. This is equivalent to 5.5 tablespoons of blood for each assessment. Peripheral blood mononuclear cells (PBMC) will be isolated by Ficoll density gradient. PBMCs will be stimulated with IL-6 for 20 minutes to activate STAT3. Phosphoproteins will be analyzed within T-cells by flow cytometry.

    Result reported is %pSTAT3+CD4+T cells at day +21.

    Measured: up to 21 days

Secondary outcomes (1)

  1. Incidence of Acute GVHD

    Cumulative incidence of acute GVHD . Participants will be monitored for clinical signs of acute GVHD. Acute GVHD will be graded per the 1995 consensus guidelines.

    Measured: up to 100 days

Timeline

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

  1. First posted7 Sep 2016 (estimated)
  2. Study start8 Jun 2017
  3. Primary completion28 Jan 2022
  4. Study completion18 Apr 2022

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
Prevention
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02891603
Sponsor's protocol ID
MCC-18783
Other IDs
5R01HL133823-02
Status last verified
Mar 2026
First submitted
1 Sep 2016
Last updated
2 Apr 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Pidala J, Walton K, Elmariah H, Kim J, Mishra A, Bejanyan N, Nishihori T, Khimani F, Perez L, Faramand RG, Davila ML, Nieder ML, Sagatys EM, Holtan SG, Lawrence NJ, Lawrence HR, Blazar BR, Anasetti C, Sebti SM, Betts BC. Pacritinib Combined with Sirolimus and Low-Dose Tacrolimus for GVHD Prevention after Allogeneic Hematopoietic Cell Transplantation: Preclinical and Phase I Trial Results. Clin Cancer Res. 2021 May 15;27(10):2712-2722. doi: 10.1158/1078-0432.CCR-20-4725. Epub 2021 Mar 22.

    PubMed 33753457

  • Betts BC, Bastian D, Iamsawat S, Nguyen H, Heinrichs JL, Wu Y, Daenthanasanmak A, Veerapathran A, O'Mahony A, Walton K, Reff J, Horna P, Sagatys EM, Lee MC, Singer J, Chang YJ, Liu C, Pidala J, Anasetti C, Yu XZ. Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation. Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):1582-1587. doi: 10.1073/pnas.1712452115. Epub 2018 Jan 30.

    PubMed 29382747

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pacritinib, Sirolimus and Tacrolimus in people with Graft Vs Host Disease and GVHD, run by H. Lee Moffitt Cancer Center and Research Institute at 2 sites in United States.

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 7 inclusion and 12 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: finished, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

Yes. Results are posted in the registry (first posted 25 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

STAT Activity (time frame: up to 21 days). 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 NCT02891603, which also lists 2 linked publications.

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 2 Apr 2026.

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