A Phase I/II GVHD Prevention Trial Combining Pacritinib With Sirolimus-Based Immune Suppression
2 other identifiers
interventional
40
1 country
2
Brief 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 unrelated allogeneic hematopoietic cell transplantation (alloHCT).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2017
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 1, 2016
CompletedFirst Posted
Study publicly available on registry
September 7, 2016
CompletedStudy Start
First participant enrolled
June 8, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 28, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 18, 2022
CompletedResults Posted
Study results publicly available
October 25, 2023
CompletedApril 2, 2026
March 1, 2026
4.6 years
September 1, 2016
July 3, 2023
March 31, 2026
Conditions
Outcome Measures
Primary Outcomes (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.
up to 21 days
Secondary Outcomes (1)
Incidence of Acute GVHD
up to 100 days
Study Arms (3)
Phase 1, Level 1: Pacritinib with Sirolimus and Tacrolimus
EXPERIMENTALAfter 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.
Phase 1, Level 2: Pacritinib with Sirolimus and Tacrolimus
EXPERIMENTALAfter 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.
Phase 2: Pacritinib with Sirolimus and Tacrolimus
EXPERIMENTALAfter 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.
Interventions
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.
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.
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).
Patients will undergo allogenic hematopoietic cell transplant (alloHCT) as a part of their standard of care treatment.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Related Publications (2)
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.
PMID: 33753457DERIVEDBetts 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.
PMID: 29382747DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Joseph Pidala, MD, PhD
- Organization
- Moffitt Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Joseph Pidala, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 1, 2016
First Posted
September 7, 2016
Study Start
June 8, 2017
Primary Completion
January 28, 2022
Study Completion
April 18, 2022
Last Updated
April 2, 2026
Results First Posted
October 25, 2023
Record last verified: 2026-03