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

NCT04118556 | Terminated Phase 2 DMC

• 2 other identifiers: DSC-BROMS-12019-002186-36
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 4

Brief Summary

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.

Conditions

GVHD, Acute

Keywords

DSC; BAT; GVHD; HSCT

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability evaluation including Severe Adverse Events (SAE).

  Adverse events will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  5 years

• Durable Response to treatment

  Durable Overall Response (DOR) day 56.

  56 days

Secondary Outcomes (8)

• Number of patients with overall response (CR+PR) at day 28

  28 days

• Rate of Survival

  1 year

• Incidence of Non-Relapse Mortality (NRM)

  1 year

• Incidence of infections

  1 year

• Change of Quality of Life

  1 year

Study Arms (2)

Decidua Stroma Cells (DSC)

EXPERIMENTAL

Placenta derived decidua stroma cells (DSC). In the first phase I part, two different dose levels will be used, 1x10\^6/kg and 3x10\^6/kg. Two doses, one week apart, will be given. The decision to proceed to the next dose level will depend on results observed at the previous dose level. The dose in the randomized part will be based on the findings in the phase I part. In the Phase II study all patients will receive 2 doses, one week apart. Depending on response, up to 6 doses in total may be given. Additional doses (beyond the first 2 doses) may be given one week apart until response.

Biological: Decidua Stroma Cells (DSC)

Best Available Treatment (BAT)

ACTIVE COMPARATOR

The BAT in this study will freely be identified by the Investigator prior to patient randomization and may include treatments such as: anti-thymocyte globulin (ATG), extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), etanercept, vedolizumab, ruxolitinib or infliximab. Dose and frequency will depend on label (where approved) and institutional guidelines for various BAT.

Drug: Best available Treatment (BAT)

Interventions

Decidua Stroma Cells (DSC) BIOLOGICAL

Placenta-derived Decidua Stroma Cells. The product consists of a viable allogeneic DSCs frozen in 5% of human serum albumin (HSA) in sodium chloride (NaCl) 0.9% and 10% dimethylsulfoxide (DMSO), that is thawed and immediately diluted in 40 mL sodium chloride (NaCl) 0.9% prior to infusion. That will give a final concentration of 2.2% HSA and 2% DMSO. DSC will be infused when steroid-refractory acute GVHD after allogenic stem-cell transplantation has been diagnosed. Two doses, one week apart, will be given to all patients. Additional doses will be used depending on response.

Decidua Stroma Cells (DSC)

Best available Treatment (BAT) DRUG

The BAT in this study will freely be identified by the Investigator prior to patient randomization and may include treatments such as: extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), etanercept, vedolizumab, ruxolitinib or infliximab. Dose and frequency will depend on label (where approved) and institutional guidelines for various BAT.

Also known as: ECP, Everolimus, Sirolimus, Etanercept, Vedolizumab, Ruxolitinib, Infliximab.

Best Available Treatment (BAT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
• Has received systemic treatment for aGvHD apart from steroids.
• Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome.
• Pregnant or lactating women.
• Significant respiratory disease.
• Presence of severely impaired renal function
• Any corticosteroid therapy for indications other than aGvHD
• Previous participation in a study of any investigational treatment agent within 30 days
• Known human immunodeficiency virus infection (HIV).
• Patients suffering on active tuberculosis or viral hepatitis
• Significant respiratory disease
• Presence of severely impaired renal or liver function
• History of progressive multifocal leuko-encephalopathy
• Patients with coagulopathy
• History of severe chronic history of heart disease

Sponsors & Collaborators

• Mats Remberger: lead
• The Swedish Research Council: collaborator

Study Sites (4)

Copenhagen Univerity Hospital

Copenhagen, 2300, Denmark

Location

Oslo University Hospital

Oslo, NO-0424, Norway

Location

Lund University Hospital

Lund, SE-221 85, Sweden

Location

Uppsala University Hospital

Uppsala, SE-75185, Sweden

Location

Related Publications (2)

• Ringden O, Baygan A, Remberger M, Gustafsson B, Winiarski J, Khoein B, Moll G, Klingspor L, Westgren M, Sadeghi B. Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease. Stem Cells Transl Med. 2018 Apr;7(4):325-331. doi: 10.1002/sctm.17-0167. Epub 2018 Mar 13.

  PMID: 29533533 RESULT

• Sadeghi B, Remberger M, Gustafsson B, Winiarski J, Moretti G, Khoein B, Klingspor L, Westgren M, Mattsson J, Ringden O. Long-Term Follow-Up of a Pilot Study Using Placenta-Derived Decidua Stromal Cells for Severe Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2019 Oct;25(10):1965-1969. doi: 10.1016/j.bbmt.2019.05.034. Epub 2019 Jun 4.

  PMID: 31173898 RESULT

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Eosinophil Cationic Protein; Everolimus; Sirolimus; Etanercept; vedolizumab; ruxolitinib; Infliximab

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Endoribonucleases; Ribonucleases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Eosinophil Granule Proteins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Organic Chemicals; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Constant Regions; Immunoglobulins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal; Antibodies

Study Officials

• Mats Remberger, Professor

  KFUE, Uppsala University Hospital, Uppsala, Sweden

  STUDY DIRECTOR

• Ulla Olsson-Strömberg, AssProfessor

  Dep of Hematology, Uppsala University Hospital, Uppsala, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 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. 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.

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: October 8, 2019
• Study Start: December 1, 2021
• Primary Completion: April 29, 2026
• Study Completion: April 29, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); NO (1); SE (2)