Phase 1 Infused Donor T Regulatory Cells in Steroid Dependent/Refractory Chronic GVHD

NCT01911039 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-27285BMT253
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic graft versus host disease (cGVHD) is a common complication of bone marrow or hematopoietic cell transplant from another person (allogeneic transplant). This study will determine if subjects with steroid dependent/refractory cGVHD can tolerate infusion of donor regulatory T cells and whether their cGVHD responds to the infusion.

Conditions

Graft Versus Host Disease; Allogeneic Hematopoietic Cell Transplant Recipient

Keywords

GVHD; cGVHD

Outcome Measures

Primary Outcomes (1)

• The frequency of adverse events related to the donor Treg infusions (e.g., grade III-IV aGVHD by the modified Keystone criteria and grade 3 or higher infusional toxicities graded according to the CTCAE v. 4)

  For infusion-related toxicities, recipients will be monitored for 1 hour after the Treg infusion. Additional toxicities which may occur during the first 28 days after the Treg infusions will count towards the assessment of safety and tolerability (DLT assessment) (e.g., development of aGVHD). Acute GVHD will be assessed using the modified Keystone criteria on Days 14, 28, 42, 56, 84 and 180 after the Treg infusion (or if the subject is exhibiting signs of aGVHD in-between study visits). Dose limiting toxicities are defined in Section 8. Only toxicities which occur during the first 28 days after the cell infusion will count towards the assessment of DLTs. A dose of Treg will be considered safe if DLTs occur in only 1/6 or 0/3 members of the cohort during the dose-escalation phase.

  Up to day 180

Secondary Outcomes (5)

• Change in absolute blood Treg levels

  Baseline to day 42

• Improvement in Failure Free Survival (FFS) over cGVHD

  At day 180

• Successful achievement of cGVHD partial response or Complete response by the NIH consensus criteria

  Up to day 180

• The ability to reduce steroid requirements to <0.25 mg/kg-day

  At day 180

• Change in >7 points on the Lee cGVHD Symptom scale relates to improvement in quality of life

  Baseline to day 180

Study Arms (1)

Regulatory T Cells

EXPERIMENTAL

Cohort 1 at 1x105 Treg cells/kg, Cohort 2 at 5x105 Treg cells/kg and Cohort 3 at 1.5x106 Treg cells/kg with an extension phase at the MTD (or maximum administered dose if the MTD is not reached).

Biological: Regulatory T Cells

Interventions

Regulatory T Cells BIOLOGICAL

Also known as: donor Treg cell

Regulatory T Cells

Eligibility Criteria

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

You may qualify if:

• Steroid dependent/refractory cGVHD defined as:
• Steroid dependent disease: Persistent cGVHD manifestations requiring a glucocorticoid dose \>= prednisone 0.25 mg/kg/day (0.5 mg/kg orally \[po\] every other day) for at least 12 weeks
• Steroid refractory disease: Progressive cGVHD manifestations despite treatment with a glucocorticoid dose \>= prednisone 0.5 mg/kg/day (1 mg/kg po every other day) for at least 4 weeks
• Participants must be receiving systemic glucocorticoid therapy for cGVHD; all immunosuppressive therapy may include but not be limited to tacrolimus, sirolimus, CellCept, cyclosporine, and systemic corticosteroid must be at stable doses for 28 days prior to the first cell infusion
• Chronic GVHD manifestations that can be followed on physical or laboratory exam; these include but are not necessarily limited to:
• Skin changes
• Oral mucosa changes
• Bronchiolitis obliterans
• Ocular changes
• Karnofsky performance status \>= 60
• Serum creatinine =\< 2 mg/dL
• Absolute neutrophil count (ANC) \> 1 x 10\^9/L
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 20 x upper limit of normal (ULN) or
• Total bilirubin =\< 10 x ULN
• Allogeneic hematopoietic cell transplant recipient

You may not qualify if:

• Original transplant utilized an unrelated donor graft
• Uncontrolled infections that are not responsive to antimicrobial therapy
• Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
• Second malignancy except for skin cancer within the last 5 years
• Received any investigational agent =\< 28 days before Treg infusions
• Received filgrastim (GCSF) treatment within one month of enrollment
• Received a donor lymphocyte infusion (DLI) or hematopoietic cell transplantation (HCT) within 3 months of enrollment
• DONOR: Evidence of active infection or viral hepatitis
• DONOR: HIV positive
• DONOR: Pregnant donor

Sponsors & Collaborators

• Laura Johnston: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Stanford University, School of Medicine

Palo Alto, California, 94305, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Laura Johnston

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 15, 2013
• First Posted: July 30, 2013
• Study Start: July 1, 2013
• Primary Completion: December 31, 2017
• Study Completion: July 31, 2018
• Last Updated: September 27, 2021

Record last verified: 2021-09

Locations

US (1)