Phase 1 Infused Donor T Regulatory Cells in Steroid Dependent/Refractory Chronic GVHD
Two investigational devices, the CliniMACS cell selection system and the BD influx highspeed cell sorter, will be used together to isolate highly purified regulatory T cells from the donor's cellular product. It is believed that using these devices in combination will produce a cellular product that is highly purified to prevent the infusion of other T cells that may contribute to graft versus host disease.
Graft Versus Host Disease
Allogeneic Hematopoietic Cell Transplant Recipient
Biological: Regulatory T Cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Safety and Tolerability Study of Infused Donor T Regulatory Cells in Steroid Dependent/Refractory Chronic Graft Versus Host Disease|
- 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) [ Time Frame: Up to day 180 ] [ Designated as safety issue: No ]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.
- Change in absolute blood Treg levels [ Time Frame: Baseline to day 42 ] [ Designated as safety issue: Yes ]The change in Treg cell counts from baseline to post infusion will be depicted in boxplots of both relative proportion and absolute numbers. Mean log (fold change) and confidence intervals will be calculated.
- Improvement in Failure Free Survival (FFS) over cGVHD [ Time Frame: At day 180 ] [ Designated as safety issue: No ]FFS is defined as the absence of a third line therapy (treatment failure). Estimated by the Kaplan-Meier product-limit method, with standard confidence limits.
- Successful achievement of cGVHD partial response or Complete response by the NIH consensus criteria [ Time Frame: Up to day 180 ] [ Designated as safety issue: No ]
- Complete Response (CR) - Complete resolution of all reversible manifestations of cGVHD. Irreversible manifestations will be defined as (NIH consensus criteria) are: ocular xerosis, esophageal stricture, and bronchiolitis obliterans.
- Partial Response (PR) - At least a 25% absolute or 50% relative change (whichever is greater) when comparing start and end measurements in one cGVHD manifestation without worsening in the other manifestations.
The results will be summarized in tabular form, with confidence intervals for the trinomial proportions.
- The ability to reduce steroid requirements to <0.25 mg/kg-day [ Time Frame: At day 180 ] [ Designated as safety issue: No ]
- Change in >7 points on the Lee cGVHD Symptom scale relates to improvement in quality of life [ Time Frame: Baseline to day 180 ] [ Designated as safety issue: No ]A one-sample t-test will be used on the change in scale from baseline to months 1, 3, and 6.
|Study Start Date:||July 2013|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Regulatory T Cells
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
Other Name: donor Treg cell
Determine the safety and tolerability of donor T regulatory (Treg) cell infusions in subjects with steroid dependent/refractory chronic graft versus host disease.
- Determine the quantitative blood Treg cell changes following the cell infusions
- Determine clinical efficacy of donor Treg cells as failure-free survival (FFS) defined by the absence of a new immunosuppressive therapy added, non-relapse mortality, and recurrent malignancy at Day 180 after the first Treg infusion
In addition to FFS, the study will measure the change in:
- cGVHD symptom burden measured by the Lee cGVHD Symptom Scale by increase in >7 points
- NIH organ-specific cGVHD scale
- The reduction in daily corticosteroid requirement of prednisone to <=0.25 mg/kg-day at Day 180 after the first Treg infusion
Please refer to this study by its ClinicalTrials.gov identifier: NCT01911039
|Contact: Joanne M Otani, RN, MSN, PHNfirstname.lastname@example.org|
|United States, California|
|Palo Alto, California, United States, 94305|
|Contact: Joanne Otani, RN, MSN, PHN 650-721-2372 mailto:email@example.com|
|Principal Investigator: Laura J Johnston, MD|
|Sub-Investigator: Sally Arai, MD, PhD|
|Sub-Investigator: Ginna Laport, MD|
|Sub-Investigator: Robert Lowsky, MD|
|Sub-Investigator: Everett Meyer, MD, PhD|
|Sub-Investigator: Joanne Otani, RN, MSN, PHN|
|Sub-Investigator: Kevin Sheehan, PhD|
|Sub-Investigator: Judith Shizuru, MD, PhD|
|Sub-Investigator: Wen Kai Weng, MD, PhD|