BMT Autologous MSCs for GvHD

NCT02359929 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB00076372
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Subjects in this study have had an allogeneic (blood or marrow cells from another person) blood or marrow transplant to treat leukemia, lymphoma or other cancer of the blood, and have now developed Graft Versus Host Disease (GVHD) that is not responding to standard treatment. GVHD is when the graft (transplanted bone marrow or blood) attacks the recipient's body. GVHD occurs early after transplant (acute) and/or sometimes months after transplant (chronic). Both forms can be life threatening; chronic GVHD can be a lifelong disabling condition. Mesenchymal stromal cells (MSCs) exist in tissues throughout the body. One place they are found is in the bone marrow and from here they can be obtained by needle aspiration, the same way bone marrow samples are obtained to test for leukemia. This study uses autologous MSCs obtained from the recipient with acute and/or chronic GVHD, which have a lower chance of being rejected. These MSCs may promote tolerance, helping the donor immune cells accept the recipient's body. This trial is being conducted as a step toward testing the long-term hypothesis that freshly cultured autologous MSC grown in platelet lysate-containing medium will modulate donor T-cell immune responses and reduce GVHD in allo-HSCT recipients. As a phase I dose escalation trial of autologous MSC in patients with acute and chronic GVHD, the main aim is to evaluate the safety of this therapy and its effects on GVHD biomarkers and T-cell phenotype

Conditions

Graft Versus Host Disease; Acute Graft Versus Host Disease; Chronic Graft Versus Host Disease

Keywords

graft versus host disease; GVHD

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of EPIC MSC2014-002 based on dose limiting toxicities (DLTs)

  Number of adverse events that are considered dose limiting toxicities (DLTs). DLTs will be defined as any grade ≥3 adverse reaction that is unexpected, or considered attributable to the MSC infusion (attribution listed as at least probable).

  6 months

Secondary Outcomes (6)

• Overall Response Rate for acute GVHD subjects

  6 months

• Overall Response Rate for chronic GVHD subjects

  6 months

• Transplant-related mortality

  6 months

• Incidence of Relapse

  6 months

• Disease-free survival

  1 year post transplant

Study Arms (3)

Dose Level 1: Infusion of MSCs

EXPERIMENTAL

First three subjects enrolled will receive a single infusion of mesenchymal stromal cells based on their individual weight

Biological: Autologous mesenchymal stromal cells (MSCs)

Dose Level 2: Infusion of MSCs

EXPERIMENTAL

Subsequent subjects enrolled will receive two infusions (a week apart) of mesenchymal stromal cells based on their individual weight

Biological: Autologous mesenchymal stromal cells (MSCs)

Dose Level 3: Infusion of MSCs

EXPERIMENTAL

Subsequent subjects enrolled will receive four infusions (a week apart) of mesenchymal stromal cells based on their individual weight

Biological: Autologous mesenchymal stromal cells (MSCs)

Interventions

Autologous mesenchymal stromal cells (MSCs) BIOLOGICAL

Infusion of MSCs delivered to each patient will depend on their weight and assigned dose level. The maximal individual dose of MSCs any patient will receive is 2 x 1000000 cells/kg.

Dose Level 1: Infusion of MSCs; Dose Level 2: Infusion of MSCs; Dose Level 3: Infusion of MSCs

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: patients must be ≥12 years old and weigh \> (25 kg) at the time of study entry.
• Patients must have received an allogeneic stem cell transplant for a hematologic malignancy.
• Must have one of the following diagnoses:
• Acute GVHD (grade II-IV) requiring systemic therapy and refractory/unresponsive to glucocorticoid (\>1 mg prednisone-equivalent/kg x 1 week)
• Chronic GVHD that is extensive and not improved despite therapy with glucocorticoid (\> 0.5 mg prednisone-equivalent/kg/day) and therapeutic doses of a calcineurin inhibitor for at least 4 weeks, or worsened within 2 weeks, or overlap syndrome not responding to glucocorticoid treatment (\>1 mg prednisone-equivalent/kg x 1 week)

You may not qualify if:

• Active invasive fungal infection requiring treatment with anti-fungal medication.
• Active viral infection requiring treatment with anti-viral medication.
• Persistence/relapse at the time of study entry of the primary malignancy for which the transplant was performed. Patients with a history of relapsed malignancy who have achieved a remission at the time of evaluation for study participation will not be excluded.
• Known T-cell donor chimerism of \<50%.
• Documented DLCO \<50% (if performed within 90 days of enrollment) or requirement for supplemental oxygen.
• Pregnancy or breastfeeding. Patients of childbearing capability should agree to use contraception.

Sponsors & Collaborators

• Emory University: lead
• CURE Foundation: collaborator

Study Sites (1)

Children's Healthcare of Atlanta/Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Stenger E, Giver CR, Langston A, Kota D, Das PK, Chinnadurai R, Galipeau J, Waller EK, Qayed M. Safety of autologous freshly expanded mesenchymal stromal cells for the treatment of graft-versus-host disease. Front Immunol. 2022 Sep 14;13:959658. doi: 10.3389/fimmu.2022.959658. eCollection 2022.

  PMID: 36189324 RESULT

MeSH Terms

Conditions

Graft vs Host Disease; Bronchiolitis Obliterans Syndrome

Condition Hierarchy (Ancestors)

Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Study Officials

• Muna Qayed, MD

  Children's Healthcare of Atlanta/Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 5, 2015
• First Posted: February 10, 2015
• Study Start: January 1, 2015
• Primary Completion: June 15, 2020
• Study Completion: January 11, 2021
• Last Updated: January 12, 2023

Record last verified: 2023-01

Locations

US (1)