A Phase I Study to Evaluate the Safety and Maximum Tolerated Dose of Momelotinib Durind and Following Hematopoietic Cell Transplantation for Patients With Myelofibrosis
This is a single-center, open-label, phase I study to determine the safety and tolerability of momelotinib in patients with myelofibrosis during and after hematopoietic cell transplantation (HCT).
• Participants must have pathologically confirmed primary myelofibrosis (PMF) according to WHO criteria or secondary myelofibrosis as defined by the IWG-MRT criteria.
‣ Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) Plus criteria OR
⁃ Intermediate-1 risk disease with at least one of the following unfavorable features known to impact the survival adversely
• Red cell transfusion dependency
∙ Unfavorable Karyotype
∙ Platelet count ≤100 x 10\^9/L
∙ Presence of a high risk molecular marker associated with worsened overall survival (ASXL1, EZH2, IDH1/2, SRSF2, U2AF1, p53)
• Participants do not have to be receiving treatment with JAK inhibitors for MF at the time of enrollment. If participants are receiving JAK inhibitor therapy with agents other momelotinib, participants must agree to be switched to momelotinib to begin Cycle 1 Day 1 on Day -7 from HCT (at the initiation of conditioning).
• Age \>18 years
• Participants must be designated to undergo allogeneic HCT with:
‣ reduced intensity conditioning regimen, and
⁃ peripheral blood stem cells as a graft source
• Participants who will undergo HCT from the following donor types are eligible:
‣ 6/6 (HLA-A, B, DR) fully matched related donor or
⁃ 8/8 (HLA-A, B, DR, C) fully matched unrelated donor. Matching in the unrelated setting must be at the allele level
• ECOG performance status ≤2 (Karnofsky ≥60%)
• The effects of momelotinib on the developing human fetus are unknown. Female patients of childbearing potential must have a negative pregnancy test, as measured by serum or urine testing. Women of childbearing potential: must agree to use highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 1 week after the last dose of momelotinib.
⁃ Male participants with women of child bearing potential partners must agree to use one of the forms of medically acceptable birth control at start of the first treatment, during the study, and for at least 6 months after the last dose. See Exclusion Criteria for effective contraception and birth control.
⁃ \- Ability to understand and the willingness to sign a written informed consent document.