IRB Study Number 24-747
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
To determine the preliminary efficacy of axatilimab in combination with ruxolitinib and to assess the contribution of axatilimab to the combination treatment effect in participants with cGVHD.
Secondary Objectives
To determine the safety and tolerability of axatilimab in combination with ruxolitinib in participants with cGVHD.
To evaluate the clinical benefit of axatilimab in combination with ruxolitinib in participants with cGVHD with respect to secondary endpoints, assessed for each treatment group.
To assess the PK of axatilimab in combination with ruxolitinib in participants with cGVHD.
Inclusion Criteria
≥ 12 years of age at the time of informed consent.
Ability to comprehend and willingness to sign a written ICF for the study. A parent/guardian should provide consent for pediatric participants unable to provide consent themselves; in addition, where applicable, pediatric participants should sign their own assent form.
New-onset moderate or severe cGVHD, as defined by the 2014 NIH Consensus Development Project Criteria for Clinical Trials in cGVHD, requiring systemic therapy (Jagasia et al 2015).
Note: Diagnosis of cGVHD requires at least 1 diagnostic feature of cGVHD or at least 1 distinctive feature plus additional tests such as biopsy, PFTs, Schirmer test, or radiographic imaging showing cGVHD in the same or another organ (see Appendix C).
Participants with single-organ, genitourinary involvement or liver involvement as the only manifestation of cGVHD are not eligible.
History of 1 allo-SCT (any type of stem cell donor, any conditioning regimen, and source of hematopoietic stem cells).
KPS score ≥ 60% if aged 16 years and older; LPS score ≥ 60% if younger than 16 years of age.
Adequate hematologic function independent of platelet transfusion and growth factors for at least 7 days prior to study entry: ANC ≥ 0.75 × 109/L and platelet count ≥ 20 × 109/L.
Willingness to avoid pregnancy or fathering children based on the criteria below.
a. Male participants with reproductive potential must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of study treatment and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed.
b. Female participants who are WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose on Day 1 and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from 14 days prior to study entry until 90 days after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed.
c. Female participants not considered to be of childbearing potential as defined in Appendix A are eligible.
Exclusion Criteria
Received more than 1 prior allo-SCT. Prior autologous HCT is allowed.
Has overlap cGVHD, defined as simultaneous presence of features or characteristics of aGVHD in a patient with cGVHD.
Note: Prior history of aGVHD with resolution of symptoms is allowed.
- Received previous systemic treatment for cGVHD, including systemic corticosteroids and extracorporeal photopheresis.
Note 1: Topical/organ-specific therapies (specified in Section 6.6.1) started prior to C1D1 are allowed and can be continued concomitantly with study treatment.
Note 2: Prior PUVA therapy or narrow-band ultraviolet B phototherapy for cGVHD is not allowed.
- Received systemic corticosteroids within 2 weeks prior to C1D1, regardless of indication.
Note: Participants with a history of aGVHD treated with systemic corticosteroids are eligible, provided corticosteroid taper was completed at least 2 weeks prior to C1D1.
- Initiated systemic treatment with CNIs or mTOR inhibitors within 2 weeks prior to C1D1.
Note: Ongoing, concomitant treatment with a CNI (ie, tacrolimus or cyclosporine) or an mTOR inhibitor (ie, sirolimus or everolimus) is allowed under the following conditions:
CNI or mTOR inhibitor had been given for GVHD prophylaxis OR
CNI or mTOR inhibitor was restarted for the management of aGVHD in a participant with a history of aGVHD in which aGVHD symptoms have resolved prior to screening. Doses may be adjusted for trough levels, with no increase in target trough range in the 2 weeks prior to start of study treatment on C1D1.
Prior treatment with a JAK inhibitor within 8 weeks before randomization. Participants who received a JAK inhibitor for the treatment of aGVHD are eligible only if they achieved a response (CR or PR) to JAK inhibitor treatment and did not discontinue due to toxicity.
Evidence of relapse of the primary hematologic disease or treatment for relapse after the allo-SCT was performed, including DLIs for the treatment of molecular relapse.
Note: Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.
Maintenance therapy for the primary hematologic disease started within 4 weeks before initiation of study treatment (Day 1) or plans to start maintenance therapy after Day 1.
Ongoing treatment with fluconazole at daily doses higher than 200 mg.
History of acute or chronic pancreatitis.
History of thromboembolic events (such as deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction) in the 6 months prior to study entry.
Active symptomatic myositis.
Known HIV seropositive status.
Note: For participants with unknown HIV status, HIV testing will be performed at screening.
Suspected active or latent tuberculosis (as confirmed by a positive QuantiFERON® test).
Severe renal impairment, that is, estimated CrCl < 30 mL/min measured or calculated by Cockcroft-Gault equation in adults and Schwartz formula in pediatric participants, or end-stage renal disease on dialysis. Participants with CrCl of 30 to 59 mL/min on treatment with fluconazole are not eligible.
Impaired liver function, defined as total bilirubin > 1.5 × ULN and/or ALT and AST > 3 × ULN in participants with no evidence of liver cGVHD.
Uncontrolled nausea, vomiting, or diarrhea attributable to cGVHD or GI conditions unrelated to GVHD that may significantly alter the absorption of oral ruxolitinib (eg, malabsorption syndrome, small-bowel resection).
Active, uncontrolled systemic bacterial, fungal, parasitic, or viral infection (CMV, Epstein-Barr virus, human herpesvirus 6, BK virus). Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, there is no evidence of infection worsening, such as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs, or radiographic findings attributable to infection.
Active HBV or HCV. Participants with pretransplant positive total HBc antibody or positive HCV antibody must have negative viral load for HBV and HCV at screening. Participants with unknown viral testing results prior to transplant must have viral load results confirming no evidence of active viral disease at screening.
Currently active significant cardiac disease, such as uncontrolled arrhythmias, uncontrolled hypertension, or Class 3 or 4 congestive heart failure as defined by New York Heart Association, or a history of myocardial infarction or unstable angina within 6 months prior to randomization.
Pregnant or breastfeeding.
Administration of live-attenuated vaccines within 4 weeks prior to the first dose of study treatment or anticipated need for live-attenuated vaccines while on study treatment.
Treatment with an investigational agent, procedure, or device within 30 days of randomization, or within 5 half-lives of the investigational product, whichever is longer.
Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator.
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. Clinically significant laboratory abnormalities requiring urgent treatment should be resolved before initiation of study treatment.
