Purpose

This is a Phase 1/2, Open-label, Dose Escalation study to investigate SNDX-6352 in subjects with active cGVHD.

Condition

Eligibility

Eligible Ages
Over 12 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Subject must be 12 years of age or older, at the time of signing the informed consent.
  2. Subjects who are allogeneic HSCT recipients with cGVHD requiring systemic immune suppression.
  3. Subjects with active cGVHD who have erythematous rash involving >25% body surface area or a NIH mouth score of >4 must have received prior ibrutinib therapy.

a. 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.

4. Subjects 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 with a life expectancy of at least 3 months.

6. Adequate organ and bone marrow functions.

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

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

Exclusion Criteria

  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 or other evidence of severe illness, uncontrolled infection or any other conditions that would make the subject, in the opinion of the Investigator, unsuitable for the study.
  4. Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
  5. Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of enrollment, unless previously treated with curative intent and must be approved by Sponsor medical monitor (e.g., 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).
  6. Female subjects who is pregnant or breastfeeding.
  7. Previous exposure to study intervention or known allergy/sensitivity to study intervention.
  8. Taking agents other than a corticosteroid and one calcineurin inhibitor (CNI) for treatment of cGVHD (This does not include agents being prescribed expressly for the treatment of acute GVHD).
  9. Receiving an investigational treatment within 28 days of study entry.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
The dose-escalation phase is a sequential group (dose-escalating) treatment study that is open-label. The dose-expansion phase is a parallel group treatment study with open-label cohorts.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohorts of escalating dose levels of SNDX-6352
Escalating dose levels of SNDX-6352 to establish the optimal biologic dose (OBD) and recommended Phase 2 dose (RP2D). IV infusion; SNDX-6352 at a dose of 0.15 mg/kg to 3 mg/kg.
  • Drug: SNDX-6352
    SNDX-6352 is a high affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor derived macrophages that mediate the disease processes involved in cGVHD.
    Other names:
    • axatilimab
Experimental
Phase 2 Dose Expansion
Phase 2, dose expansion, is an open-label design, evaluating the 1 mg/kg dose in a larger sample size. IV infusion; SNDX-6352 at a dose of 1 mg/kg.
  • Drug: SNDX-6352
    SNDX-6352 is a high affinity antibody targeting the colony stimulating factor 1 receptor (CSF-1R). CSF-1R signaling has been demonstrated in nonclinical studies to be the key regulatory pathway involved in the expansion and infiltration of donor derived macrophages that mediate the disease processes involved in cGVHD.
    Other names:
    • axatilimab

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294
Contact:
Antonio DiStasi, MD
adistasi@uabmc.edu

More Details

Status
Recruiting
Sponsor
Syndax Pharmaceuticals

Study Contact

Christine Quaranto
781-684-9824
cquaranto@syndax.com

Detailed Description

This is dose escalation and dose expansion study in patients with active chronic graft versus host disease (cGVHD) who have received at least 2 lines of prior therapy.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.