Decidua Stroma Cells for Steroid Resistent Acute Graft-versus-host Disease After Allo-HSCT
NCT ID: NCT04118556
Last Updated: 2024-12-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
50 participants
INTERVENTIONAL
2021-12-01
2031-12-31
Brief Summary
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No cross-over are planned in the second stage of the study.
Detailed Description
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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
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
No cross-over are planned in the second stage of the study.
TREATMENT
NONE
Study Groups
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Decidua Stroma Cells (DSC)
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.
Decidua Stroma Cells (DSC)
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.
Best Available Treatment (BAT)
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.
Best available Treatment (BAT)
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.
Interventions
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Decidua Stroma Cells (DSC)
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.
Best available Treatment (BAT)
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Signed written study informed consent once SR-aGvHD is confirmed.
Exclusion Criteria
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.
18 Years
ALL
No
Sponsors
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The Swedish Research Council
OTHER_GOV
Mats Remberger
OTHER
Responsible Party
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Mats Remberger
Professor
Principal Investigators
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Mats Remberger, Professor
Role: STUDY_DIRECTOR
KFUE, Uppsala University Hospital, Uppsala, Sweden
Ulla Olsson-Strömberg, AssProfessor
Role: PRINCIPAL_INVESTIGATOR
Dep of Hematology, Uppsala University Hospital, Uppsala, Sweden
Locations
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Copenhagen Univerity Hospital
Copenhagen, , Denmark
Oslo University Hospital
Oslo, , Norway
Gothenburg University Hospital
Gothenburg, , Sweden
Lund University Hospital
Lund, , Sweden
Karolinska University Hospital
Stockholm, , Sweden
Uppsala University Hospital
Uppsala, , Sweden
Countries
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Central Contacts
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Facility Contacts
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Brian T Kornblit, AssProf
Role: primary
Tobias Gedde-Dahl, Professor
Role: primary
Stig Lenhoff, AssProf
Role: primary
Ulla Olsson-Strömberg, AssProf
Role: primary
References
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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.
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.
Other Identifiers
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2019-002186-36
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
DSC-BROMS-1
Identifier Type: -
Identifier Source: org_study_id