Decidua Stroma Cells for Steroid Resistent Acute Graft-versus-host Disease After Allo-HSCT

A Multicenter, Open-label, Randomized, Phase I/II Clinical Trial Comparing Safety and Durable Overall Response Day 56 in Patients With Steroid Resistent Acute GvHD After Allogeneic Hematopoietic Stem Cell Transplant Treated With DSC or BAT

A randomized (1:1) phase II open label study of DSC compared to Investigator choice Best Available Therapy (BAT) in allogeneic hematopoietic stem cell transplant recipients with Grades II-IV steroid refractory acute graft vs. host disease in the second part of the study. Patients will receive 2 doses of DSC. Additional doses (up to 4 doses) may be given depending on response.

No cross-over are planned in the second stage of the study.

Main inclusion criteria:

Adult patients (age ≥ 18 years) with steroid refractory (SR) acute GvHD (aGVHD) grades II-IV after allo-HSCT.

Signed written study informed consent once SR-aGvHD is confirmed.

Main exclusion criteria:

Presence of an active uncontrolled infection requiring treatment. Has received systemic treatment for aGvHD apart from steroids. Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome. Known human immunodeficiency virus infection (HIV). Patients suffering on active tuberculosis or viral hepatitis. Significant respiratory disease Presence of severely impaired renal function Patients with coagulopathy Pregnant or nursing (lactating) women Malignancy that has required treatment in the previous two years Any condition that would, in the Investigator's judgment, interfere with full participation in the study.

Design:

The trial is a Phase II, randomized (1:1), open label study investigating the efficacy and safety of DSC vs. BAT added to the patient's immunosuppressive regimen in adults with SR-aGvHD.

The primary objectives will be safety and to compare durable overall response (DOR) at 56 days after randomization between patients receiving DSC with patients receiving BAT as treatment for SR acute GvHD grades II-IV. Target enrollment is 50 patients, 25 in the DSC treatment-arm and 25 in the BAT arm. Patients will be given the optimal dose of DSC from the Phase I, dose escalating part of the study, as mentioned above. At least 2 doses of DSC will be given one week apart. Additional doses of DSC (maximum 4 doses) may be given depending on response. Additional doses (beyond the first 2 doses) may be given one week apart until response, or whenever needed if aGVHD flare occur within 6 months after randomization (EOT).

BAT: Investigator's choice Best Available Therapy (BAT) will vary depending upon Investigator's choice identified prior to randomization. Dose and frequency will depend on label (where approved) and institutional guidelines for various BAT.

Primary objective

• Assess the Safety of DSC.
• Durable Overall Response (DOR) at Day 56.

Secondary objectives

• To assess Overall Response Rate (ORR) at day 28
• To assess 1-year Overall Survival (OS)
• To assess 1-year Non-Relapse Mortality (NRM)
• To assess incidence of infections

Exploratory objectives

• To assess the cumulative steroid dose until Day 56 and Day 90
• To assess Event-Free Survival (EFS)
• To assess incidence of Malignancy Relapse/Progression
• To measure the incidence of chronic GvHD
• To measure immune reconstitution
• To evaluate changes in Patient Reported Outcomes

Inclusion Criteria:

1. Adult patients (age ≥ 18 years) with steroid refractory acute GvHD grades II-IV after allo-HSCT.
2. Signed written study informed consent once SR-aGvHD is confirmed.

Exclusion Criteria:

1. Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
2. Has received systemic treatment for aGvHD apart from steroids.
3. Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome.
4. Pregnant or lactating women.
5. Significant respiratory disease.
6. Presence of severely impaired renal function
7. Any corticosteroid therapy for indications other than aGvHD
8. Previous participation in a study of any investigational treatment agent within 30 days
9. Known human immunodeficiency virus infection (HIV).
10. Patients suffering on active tuberculosis or viral hepatitis
11. Significant respiratory disease
12. Presence of severely impaired renal or liver function
13. History of progressive multifocal leuko-encephalopathy
14. Patients with coagulopathy
15. History of severe chronic history of heart disease
16. Any condition that would, in the Investigator's judgment, interfere with full participation in the study.