Early Treatment of Acute Graft Versus Host Disease With Bone Marrow-Derived Mesenchymal Stem Cells and Corticosteroids

NCT02379442 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 15008815-H-0088
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Sometimes after stem cells are transplanted, donor cells attack the recipient s cells and cause tissue damage. This is called acute graft-versus-host-disease (GVHD). Researchers want to see if bone marrow-derived mesenchymal stem cells (BMSC) can help treat GVHD. BMSC can travel in the body and help repair tissue. The BMSC in this study were grown from bone marrow from healthy volunteers. Objectives: \- To test whether BMSC are safe to use soon after GVHD is diagnosed and to see how the body s immune system responds to BMSC. Eligibility: \- People over 4 years old who had a stem cell transplant at NIH and now have acute GVHD. People who have had certain previous immunosuppressive therapy may be ineligible. Design:

• Participants will be screened with medical history, physical exam, and blood tests. They will have a GVHD exam, including skin and stool tests. They must have a functioning central line.
• Participation will last 11 weeks: 4 8 weeks of cell infusions, then follow-up for the rest of the weeks.
• Up to 12 cell infusions:
• Participants will come to the clinic twice weekly.
• They will get medicine to prevent side effects (like Tylenol and Benadryl).
• BMSC will be given through a small plastic tube in an arm vein or through an IV catheter. It will last 20 60 minutes.
• Participants will be monitored for 1 hour.
• Follow-up visits: Up to twice a week, participants will have physical exam and blood tests. They may have a GVHD exam.
• Participants who have a tissue biopsy outside the study will be asked to send a sample to the study.

Conditions

Graft-Versus-Host Disease

Keywords

Graft-Versus-Host Disease; Corticosteroids; Mesenchymal Stromal Cell; Adoptive Cellular Therapy

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects Without a Treatment Related Severe Adverse Event

  The number of subjects without a treatment related severe adverse event (TRSAE) within 56 days of treatment.

  56 days

Study Arms (1)

1

EXPERIMENTAL

Target dose of 2 times 106 MSC/kg for up to 12 doses

Biological: MSC

Interventions

MSC BIOLOGICAL

MSC are an adherent, fibroblast-like cell population found in the bone marrow. Allogeneic MSC for treatment can be grown from bone marrow aspirates or biopsies of normal donors.

1

Eligibility Criteria

• Age: 4 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• History of any grade acute GVHD requiring systemic therapy after allogeneic stem cell transplant or DLI.
• Subjects must have received an allogeneic stem cell transplant at NIH and be diagnosed with acute GVHD. Acute GVHD is defined using the NIH consensus definition inclusive of classic acute (less than or equal to 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features) AND persistent/recurrent/late onset acute (\> 100 days after transplant or DLI, presence of acute GVHD features, absence of chronic GVHD features). Subjects with stage I and II skin only (overall Grade I) or isolated upper gastrointestinal involvement are eligible if the treating physician deems that systemic corticosteroid treatment is indicated. Biopsy confirmation of GVHD is desirable, but not required for study entry because enrollment should not be delayed awaiting biopsy or pathology results. Patients must be diagnosed with a first episode of acute GVHD requiring systemic corticosteroids and associated with preceding administration of a cellular therapy including stem cells and donor lymphocyte infusion. Patients who were treated for GVHD associated with another cellular therapy product (e.g. prior allogeneic transplant or DLI) will be allowed into the study.
• Previous immunosuppressive therapy
• The patient must have received no systemic immune suppressive therapy for treatment of new acute GVHD (e.g. pentostatin, etanercept, denileukin difitox, etc.), except for a maximum 120 hours prior corticosteroid therapy. This does not include immune suppressive therapy for GVHD prophylaxis (e.g. calcineurin inhibitor, sirolimus, MMF, etc.). It is expected that most patients will be receiving GVHD prophylaxis as part of their transplant regimen, thus patients developing acute GVHD while on GVHD prophylaxis will still be considered eligible. Concurrent or addition of locally-acting steroid therapy (skin creams, oral budesonide, or any other locally-acting steroid preparation) is allowed.
• There is one exception to the above stipulations: Use of the oral medication MMF (in addition to systemic corticosteroids) for the treatment of acute GVHD will be allowed. MMF is commonly given early in the treatment of acute GVHD, but it has not been shown to improve outcomes compared to steroids alone in a randomized, prospective study; therefore, treatment with MMF will not exclude patients from BMSC treatment.
• Age: Age greater than or equal to 4 years old will be allowed.
• Birth control: Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.
• Informed consent: Signed informed consent and/or assent is required. Assent and educational materials will be provided to, and reviewed with, patients under the age of 18. The informed consent process will begin at recognition of patient eligibility.

You may not qualify if:

• Breast feeding or pregnant females (due to unknown risk to fetus or newborn).
• Known allergy to gentamicin.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Holtan SG, Pasquini M, Weisdorf DJ. Acute graft-versus-host disease: a bench-to-bedside update. Blood. 2014 Jul 17;124(3):363-73. doi: 10.1182/blood-2014-01-514786. Epub 2014 Jun 9.

  PMID: 24914140 BACKGROUND

• Kersting S, Koomans HA, Hene RJ, Verdonck LF. Acute renal failure after allogeneic myeloablative stem cell transplantation: retrospective analysis of incidence, risk factors and survival. Bone Marrow Transplant. 2007 Mar;39(6):359-65. doi: 10.1038/sj.bmt.1705599.

  PMID: 17342159 BACKGROUND

• Martin PJ, Rizzo JD, Wingard JR, Ballen K, Curtin PT, Cutler C, Litzow MR, Nieto Y, Savani BN, Schriber JR, Shaughnessy PJ, Wall DA, Carpenter PA. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2012 Aug;18(8):1150-63. doi: 10.1016/j.bbmt.2012.04.005. Epub 2012 Apr 14.

  PMID: 22510384 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Limitations and Caveats

One subject completed the protocol, and the FDA placed the study on hold due to NIH operational issues. Since the cellular product of bone-marrow derived mesenchymal stem cells is no longer available, the protocol was terminated on December 13, 2017.

Results Point of Contact

• Title: Sawa Ito, MD
• Organization: NHLBI, NIH

itos3@upmc.edu

301-326-5233

Study Officials

• Sawa Ito, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: March 5, 2015
• Study Start: February 23, 2015
• Primary Completion: December 13, 2017
• Study Completion: December 13, 2017
• Last Updated: May 1, 2019
• Results First Posted: May 1, 2019

Record last verified: 2017-12-13

Locations

US (1)