Phase I clinical trial with umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) for treatment-resistant severe acute graft-versus-host disease (GVHD)

JRCT ID: jRCT2033180077

Registered date:11/01/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: First line treatment-resistant Grade II to IV acute graft-versus-host disease (GVHD)
• Date of first enrollment: 17/07/2018
• Target sample size: 6
• Study type: Interventional

Intervention(s)

Intravenous of IMSUT-CORD with dose escalation by 3+3 design:
Cohort 1 dose:1x10^6cells /kg,
Cohort 2 dose:2x10^6 cells /kg,
Cohort -1 dose:5x10^5 cells /kg

After safety confirmation at cohort 1, proceed to cohort 2. If two patients reveal DLT in at cohort 1, cohort -1 will be tested.
One cycle is defined as twice a week administration, and standard treatment is 2 cycles of administration. Up to two cycles of administration (total four cycles) is allowed for patients with no significant adverse effects and Partial response (PR) or Mixed response (MR).

Outcome(s)

Primary Outcome

Safety:
1) Incidence of Dose Limited Toxicity (DLT) and determination of optical dose for phase II studies.
2) Evaluation of adverse events such as the rate of events, until 11 weeks after the last administration of IMSUT-CORD.
3) Statistical evaluation of laboratory tests until 11 weeks after the last administration of IMSUT-CORD.

Secondary Outcome

Efficacy:
1) Overall response and change of stage/grading of organ damages by acute GVHD at 11 weeks after the last administration of IMSUT-CORD
2) Overall survival (OS)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 70age old
• Gender: Both

Include criteria

1. Patients with grade II to IV acute GVHD. Pathological diagnosis is required, if possible.
2. Patients resistant to standard therapy with glucocorticoid.
3. Patients who can give their consent by the written form.

Exclude criteria

1. Patients NOT treated with standard first-line treatment with glucocorticoid for acute GVHD (except for prevention therapy for acute GVHD).
2. Patients treated with hematopoietic stem cell transplantation for hematopoietic malignancies under no remission, except for myelodysplastic syndrome with or without leukemic transition and myeloproliferative diseases.
3. Patients with following severe complications within 14 days before registration.
a) Cardiac function: Ejection fraction <40%
b) Pulmonary function: SpO2 < 90% or SpO2 < 95% under oxygen inhalation.
c) Renal function: serum creatinine -> 2 times of upper limit of institutional normal range (ULN).
d) Liver function: serum total bilirubin ->3 times of ULN, AST/ALT -> 5 times of ULN.
4. Pregnant/possible pregnant and nursing woman. Patients refuse to contraception.
5. Patients positive for HIV antibodies, HTLV-I antibodies, HBs antigen, and HCV antibodies.
6. Therapy resistant hypertension
7. Patient who have allergy against reagents used for processing, such as amphotericin B, gentamicin. Patients treated as emergency for adverse reaction of DMSO.
8. Investigators decision as not eligible.

Related Information

• Primary Sponsor: Tojo Arinobu
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development
• Secondary ID(s): UMIN000032819