IRB Study Number 24-1022
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
• To assess the safety and tolerability of vimseltinib in participants with cGVHD
• To determine the recommended dose(s) of vimseltinib for further development in participants with cGVHD
Secondary Objectives
• To evaluate efficacy and durability of response of vimseltinib in participants with cGVHD
• To assess the plasma PK of vimseltinib in participants with cGVHD
Inclusion Criteria
Male or female ≥18 years of age.
Must be allogeneic HSCT recipients with moderate to severe cGVHD requiring systemic immune suppression. May have persistent active aGVHD and cGVHD manifestations (overlap syndrome), per 2014 NIH cGVHD Criteria.
Participants with active cGVHD who have received and failed at least 2 prior lines of systemic therapy. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH cGVHD Criteria.
Karnofsky Performance Scale of ≥60.
Stable dose of systemic corticosteroids up to 1 mg/kg/d prednisone equivalents is permitted but not required. If being taken, participants should be on a stable dose of corticosteroids for at least 2 weeks prior to Cycle 1 Day 1.
Adequate organ and bone marrow functions at screening by site’s local laboratory:
a. Absolute neutrophil count ≥1 × 109/L (without growth factors within 1 week of the first dose of study drug);
b. Platelet count ≥50 × 109/L (without transfusion or thrombopoietin or thrombopoietin analogs within 2 weeks of study entry);
c. Total bilirubin, ALT, and AST ≤ULN;
− For participants with suspected or confirmed liver cGVHD, ALT, AST, and ALP ≤3× ULN and total bilirubin <6 mg/dL;
d. Creatinine clearance ≥30 mL/min based on the Cockcroft-Gault formula.
Female participants of childbearing potential must have a negative serum β-hCG pregnancy test at screening and a negative pregnancy test on Cycle 1 Day 1 prior to the first dose of study drug.
Participants of reproductive potential agree to follow the contraception requirements outlined in Appendix 1.
Capable of understanding and complying with the protocol and giving signed informed consent.
Exclusion Criteria
Has aGVHD without manifestations of cGVHD.
Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
Prior use of CSF1R inhibitor for cGVHD.
History or other evidence of severe illness, uncontrolled infection, or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
Left ventricular ejection fraction <40% based on the echocardiogram at screening.
Active, uncontrolled HIV infection, AIDS, or those who are currently taking contraindicated medications for HIV control. HIV-seropositive participants who are healthy and low-risk for AIDS-related outcomes could be considered eligible. HIV infected participants must be on ART and have well-controlled HIV infection/disease defined as follows:
a. Participants on ART must have a CD4+ T-cell count >350 cells/mm3 at the time of screening
b. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to screening
- Active, uncontrolled HBV or HCV infection
a. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to screening
b. Participants with a history of HCV infection are eligible if their HCV viral load is undetectable at screening (Note: Participants must have completed curative anti-viral therapy at least 4 weeks prior to screening)
- History of malignancy except for:
a. the underlying malignancy for which the transplant was performed
b. malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to enrollment and felt to be at low risk for recurrence by treating physician (for example, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection)
Female participants who are pregnant or breastfeeding.
Previous exposure to vimseltinib or known allergy/sensitivity to any component of vimseltinib.
Taking agents other than a corticosteroid and 1 CNI, mTOR inhibitor, or MMF for cGVHD.
a. For participants with overlap syndrome, this does not include agents being prescribed expressly for the treatment of aGVHD.
Ongoing participation in an interventional study or prior participation within 30 days of screening or within 5 half-lives of the investigational product, if known (whichever is longer). Ongoing participation in a noninterventional study (including observational studies) is permitted.
Malabsorption syndrome or other illness that could affect oral absorption as judged by the Investigator.
Receive concurrent treatment with any prohibited medications:
a. Acetaminophen usage exceeding 3 g/day
b. Proton-pump inhibitors taken within 7 days prior to the first dose of study drug
c. Medications that are BCRP or OCT2 substrates (taken within 4 days or 5× the half-life [whichever is longer] prior to the first dose of study drug)
d. Medications that are strong inducers or strong inhibitors of P-gp (taken within 7 days or 5× the half-life [whichever is longer] prior to the first dose of study drug)
e. Prophylactic use of myeloid growth factors (eg, GCSF, GM-CSF) within 1 week of the first dose of study drug
f. Ruxolitinib or belumosudil taken within 1 week prior to first dose of study drug
Major surgery within 14 days of the first dose of study drug; following major surgeries >14 days prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence.
Known current alcohol abuse, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the participant to safety risks.
