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

MCC-18783

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).

2017-06-08

2022-01-28

2022-04-18

Completed

Early phase I

40

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

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2024-03-25