Intravenous Administration of RGI-2001 in Patient Undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT)
This is a first in man clinical trial that is designed as a two part study in patients undergoing AHSCT. RGI-2001 is believed to have immunomodulating effects that may expand regulatory T-cells and other beneficial cells to modulate the intensity of GvHD after the AHSCT procedure. All patients receive study medication.
In Part 1 (Dose Escalation Phase), patients will receive a single intravenous administration of RGI-2001 approximately 30 minutes after completion of the AHSCT, with the dosage based upon the assigned treatment cohort and body weight. Eligible patients will be enrolled in up to four to six centers in the United States. Patients who are undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT) will be enrolled in a sequential group dose-escalating fashion to determine the safety, tolerability, pharmacokinetic profile, and the MTD or MFD of RGI-2001. It is anticipated that up to seven dose levels will be evaluated in Part 1, with an option for an additional cohort if the MTD is not reached and pharmacodynamic markers suggest higher doses are warranted.
In Part 2 (Expansion Phase), one or more doses below the MTD or MFD will be selected based on a potential correlation between GvHD and biological activity to further assess safety and biologic activity. Approximately 30 patients will be enrolled in Part 2 of the study.
Patients will be monitored for safety for 29 days after AHSCT. All patients in part 1 and 2 of this study will be followed for 100 days following AHSCT for the incidence of acute GvHD.
Prevention of GvHD in Patients With Hematological Malignancies Undergoing AHSCT
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-Label, Multicenter, Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravenous Administration of RGI-2001 in Patient Undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT)|
- The maximum tolerated dose (MTD) or maximum feasible dose (MFD) of RGI-2001 [ Time Frame: By day 29 ] [ Designated as safety issue: Yes ]
The primary outcome measures are:
- The incidence and severity of adverse events
- The maximum tolerated dose (MTD) or maximum feasible dose (MFD) of RGI-2001, administered as a single intravenous infusion approximately 30 minutes after AHSCT
- Pharmacodynamic Effects [ Time Frame: Within 101 days from AHSCT ] [ Designated as safety issue: Yes ]Evaluate biomarkers to assess the potential pharmacodynamic effects of RGI-2001 through biomarkers and cytokine assessments. Exploratory biomarkers for efficacy in reducing GvHD include IL-2R, TNFR1, HGF. Cytokines will be evaluated for both safety and for evidence of mechanism of action and include IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, MIG, TNF-α and IFN-γ.
- Pharmacokinetics of RGI-2001 [ Time Frame: Within first 8 days ] [ Designated as safety issue: No ]Obtain pharmacokinetic parameters such as Cmax, Cmin, Tmax, AUC and half-life of the study drug in plasma.
- Efficacy in reducing the intensity of GvHD [ Time Frame: Within the first 101 days after AHSCT ] [ Designated as safety issue: No ]The time to onset, peak intensity and course of GvHD after the AHSCT procedure will be monitored according to the Modified Keystone Criteria for Acute Graft-Versus-Host Disease.
- Optimal Dose of RGI-2001 [ Time Frame: Within first 101 days after AHSCT ] [ Designated as safety issue: No ]Determine optimal doses of RGI-2001 for further evaluation based on pharmacodynamic response and effectiveness in reducing the intensity of GvHD
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||August 2013|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Dose escalation group in part 1 of this study will include 3 to 6 patients each group and up to 7 dose groups. In part 2 of this study the best dose or doses determined from part 1 will be administered in up to 30 persons.
RGI-2001 is a liposomal formulation of the α-galactosylceramide class of compound [(2S,3S,4R)-1-o-(alpha-D-galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol]. RGI-2001 is provided as an intravenous administration after AHSCT is complete. A single administration of RGI-2001 will be used in this trial. The study will last for 101 days in total; 29 days for safety and 101 days for evaluation of GvHD.
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|United States, California|
|UCSD Moores Cancer Research Institute||Recruiting|
|San Diego, California, United States, 93093|
|Contact: Edward Ball, MD 858-822-6842 email@example.com|
|Principal Investigator: Edward (Ted) Ball, MD|
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|Stanford, California, United States, 94305|
|Contact: Robert Negrin, MD 650-723-0822 firstname.lastname@example.org|
|Contact: Laura Johnston, MD 650-723-0822 email@example.com|
|Principal Investigator: Robert Negrin, MD|
|Sub-Investigator: Laura Johnston, MD|
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|Boston, Massachusetts, United States, 02114|
|Contact: Yi-Bin Chen, MD 617-724-1124 YCHEN6@PARTNERS.ORG|
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|Ohio State University Comprehensive Cancer Center - The James||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Yvonne A Efebera, MD 614-293-2268 firstname.lastname@example.org|
|Contact: Steven Devine, MD 614-293-5655 email@example.com|
|Principal Investigator: Yvonne A. Efebera, MD|
|Sub-Investigator: Steven Devine, MD|
|United States, Washington|
|Fred Hutchinson Cancer Research Center||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Paul Martin, MD 206-667-5000 firstname.lastname@example.org|
|Contact: Terry Furlong 206-667-5000 email@example.com|
|Principal Investigator: Paul Martin, MD|