Steroid Refractory Graft Versus Host Disease
Conditions
Keywords
gvhd, Tregs, graft vs. host disease, steroid refractory, steroid refractory GVHD, CK0802, T regulatory cells, CK0802 Tregs
Brief summary
The purpose of this study is to determine the efficacy and safety of CK0802 Tregs for treatment of refractory GVHD (graft-versus-host disease)
Detailed description
This clinical trial will be conducted in two parts where the first part of Phase 1b will determine the safety and tolerability of CK0802 in patients with steroid refractory GVHD and the second part of Phase 2a will examine the preliminary efficacy of CK0802 in patients with steroid refractory GVHD
Interventions
BIOLOGICALCK0802 (Allogeneic, Cryopreserved, Cord blood-derived T-regulatory cells, cells that are not HLA matched)
Subjects will receive seven planned doses of CK0802 on study day +1, +3 (+/-1 day), +5 (+/-1 day), +7 (+/- 2 day), +14 (+/- 3 days), +21 (+/-3 days) and +28 (+/-3 days). A total of 7 doses will be administered. If Day 29 assessment shows PR or MR, then 4 additional weekly infusion of CK0802 Tregs can be administered (study days: 35 (+/- 2 day), 42 (+/- 2 day), 49 (+/- 2 day), and 55(+/- 2 day)), for a total of 11 infusions
Sponsors
Cellenkos, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multiple doses of CK0802 will be administered intravenously over approximately a month
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Age ≥12 years old (first 3 subjects will be ≥ 18 years) * 2\. Grade 2-4 acute GVHD (aGVHD) at baseline * 3\. No other prior aGVHD treatment * 4\. Steroid Refractory * Progressed after 3 days of treatment with 2 mg/kg methylprednisolone (MPE) * No improvement after 7 days of treatment with 2 mg/kg MPE * Progressed to a new organ after treatment with 1 mg/kg MPE for skin or upper gastrointestinal (UGI) aGVHD * Progressed from nadir during or after a steroid taper * 5\. Female subjects of childbearing potential (FPCP) must have a negative urine or serum pregnancy test. * 6\. Agreed to abide by all protocol required procedures including study-related assessments, visits and long term follow up. * 7\. Willing and able to provide written informed consent. * 8\. Signed informed consent
Exclusion criteria
* 1\. 30 days prior treatment with any other investigational agent after allogeneic HSCT. * 2\. Known HIV seropositivity. * 3\. Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The Protocol PI is the final arbiter of eligibility. * 4\. Subjects with uncontrolled inter-current illness that in the opinion of the investigator would place the subject at greater risk of severe toxicity and/or impair the activity of CK0802. * 5\. Subjects who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b | Day +29 | Dose limiting toxicities of CK0802 in SR GVHD as assessed by the incidence and severity of AE and SAEs determined by the NCI-CTCAE Version 6.0. Non-Hematologic: Any ≥ Grade 3 non-hematologic AE as per CTCAE v6.0 Hematologic: Any new or worsened Grade 4 neutropenia, thrombocytopenia, or anemia compared with baseline that persists for \>7 days despite supportive care and is not clearly and incontrovertibly attributable to the underlying disease or another extraneous cause. Death: Death within 28 days that is not clearly and incontrovertibly attributable to the underlying disease or another extraneous cause |
| Phase 2a | D +29 | Overall Response (OR) at day +29. Overall response (OR) will include complete response (CR) and partial response (PR). Response to be determined from the maximum acute GVHD stage and grade in each organ. Complete Response (CR): Stage 0 in all organs (skin, liver, and GI tract) and no intervening additional therapy Partial Response (PR): Improvement of at least 1 stage in 1 or more organs without progression in other organs, and no intervening additional therapy Overall Response (OR): Includes both CR and PR Very Good PR (VGPR): Improvement by at least one stage in one or more organs and * Skin: No rash, or bullae, and residual erythematous rash involving \<25% of the body surface * Liver: Total serum bilirubin concentration of \<2 mg/dL or \<25% of baseline at enrollment * Gut: Tolerating food or enteral feeding, predominantly formed stools, no overt GI bleeding or abdominal cramping, no more than occasional nausea or vomiting * No intervening additional therapy |
Contacts
CONTACTClinical Trial Specialist
Outcome results
None listed