A Study of Axatilimab at 3 Different Doses in Patients With Chronic Graft Versus Host Disease (cGVHD)

Overview

About this study

The purpose of this study is to assess SNDX-6352, or Axatilimab, for individuals who have active chronic recurrent or refractory Graft versus Host Disease (cGVHD) whom have used at least two previous treatments and have not had an improvement in symptoms. This study evaluates the effectiveness, safety, and tolerability of axatilimab at three different dose levels. Participants can receive axatilimab for up to two years and could be in the study up to 28 months.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

1. Participants must be 2 years of age or older, at the time of signing the informed
consent.

2. Participants who are allogeneic hematopoietic stem cell transplantation (HSCT)
recipients with active cGVHD requiring systemic immune suppression. Active cGVHD is
defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus
Development Project on Criteria for Clinical trials in cGVHD.

3. Participants with refractory or recurrent active cGVHD despite at least 2 lines of
systemic therapy.

- Refractory disease defined as meeting any of the following criteria:

- The development of 1 or more new sites of disease while being treated for
cGVHD.

- Progression of existing sites of disease despite at least 1 month of
standard or investigation therapy for cGVHD.

- Participants who have not achieved a response within 3 months on their prior
therapy for cGVHD and for whom the treating physician believes a new
systemic therapy is required.

- Recurrent cGVHD is active, symptomatic disease (after an initial response to
prior therapy) as defined, based on the NIH 2014 consensus criteria, by
organ-specific or global assessment or for which the physician believes that a
new line of systemic therapy is required.

4. Participants may have persistent, active acute and cGVHD manifestations (overlap
syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for
Clinical trials in cGVHD.

5. Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance
Score of ≥60 (if aged <16 years)

6. Adequate organ and bone marrow functions evaluated during the 14 days prior to
randomization.

7. Creatinine clearance (CrCl) ≥30 milliliter/minute/1.73 square meter based on the
Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric
participants.

8. Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.

9. Concomitant use a of systemic corticosteroid is allowed but not required. Topical and
inhaled corticosteroid agents are allowed. If a participant is taking corticosteroids
at study randomization, they must be on a stable dose of corticosteroids for at least
2 weeks prior to Cycle 1 Day 1.

10. Concomitant use of CNI or sirolimus is allowed but not required.

11. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and protocol.
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.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. Has acute GVHD without manifestations of cGVHD.

2. Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of
the underlying cancer or post-transplant lymphoproliferative disease at the time of
screening.

3. History of acute or chronic pancreatitis.

4. History of myositis.

5. 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.

6. Participants with acquired immune deficiency syndrome (AIDS).

7. Hepatitis B (defined as hepatitis B virus [HBV] surface antigen positive and HBV core
antibody positive, with positive HBV deoxyribonucleic acid [DNA], or HBV positive core
antibody alone with positive HBV DNA. Hepatitis C (defined as positive hepatitis C
[HCV] antibody with positive HCV ribonucleic acid [RNA]).

8. Diagnosed with another malignancy (other than malignancy for which transplant was
performed) within 3 years of randomization, unless previously treated with curative
intent and approved by Sponsor's Medical Monitor (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).

9. Female participant who is pregnant or breastfeeding.

10. Previous exposure to CSF1-R targeted therapies.

11. Taking agents for treatment of cGVHD other than corticosteroids and either a CNI or
sirolimus is prohibited.

12. For approved or commonly used agents, other than corticosteroids, CNI and sirolimus, a
washout of 2 weeks or 5 half-lives, whichever is shorter, is required at study
enrollment.

13. Receiving another investigational treatment within 28 days of randomization.

14. Participants should not be participating in any other interventional study. Pediatric
participants are encouraged to also participate in the ongoing developmental studies
of the Pediatric cGVHD Symptom Scale (PCSS).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 11/7/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Mithun Shah, M.D., Ph.D.

Closed for enrollment

Contact information:

Jordan Scheevel

(507) 422-4126

Scheevel.Jordan@mayo.edu

Jacksonville, Fla.

Mayo Clinic principal investigator

Madiha Iqbal, M.B.B.S., M.D.

Closed for enrollment

Contact information:

Veronica Munet Diaz M.P.H.

(904) 953-3375

Munet-Diaz.Veronica@mayo.edu

More information

Publications

Publications are currently not available