Intravenous Administration of RGI-2001 in Patient Undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT)
This study is currently recruiting participants.
Verified January 2012 by Regimmune Inc.
Sponsor:
Regimmune Inc.
Collaborator:
Pacific-Link Regulatory Consulting LLC
Information provided by (Responsible Party):
Regimmune Inc.
ClinicalTrials.gov Identifier:
NCT01379209
First received: June 17, 2011
Last updated: January 13, 2012
Last verified: January 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Prevention of GvHD in Patients With Hematological Malignancies Undergoing AHSCT |
Drug: RGI-2001 |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| 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) |
Resource links provided by NLM:
Further study details as provided by Regimmune Inc.:
Primary Outcome Measures:
- 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
Secondary Outcome Measures:
- 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
| Estimated Enrollment: | 48 |
| 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) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: RGI-2001
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.
|
Drug: RGI-2001
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.
Other Names:
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients with hematological malignancies or myelodysplastic syndrome undergoing myeloablative therapy and a first allogeneic HSCT (AHSCT)
- Male or female, age ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) status of 0-2 or Karnofsky Performance Status (KPS) of > 60
Part 1 Dose Escalation AHSCT Procedure:
- Patients with hematological malignancies or myelodysplastic syndrome undergoing a first AHSCT procedure and who are in their 2nd or subsequent remission
- Type of allograft: Unrelated allogeneic hematopoietic stem cell transplant donor with no more than 1 HLA allele or antigen mismatch.
- Source of allograft: Unmodified (non-manipulated) bone marrow.
- Anti-graft versus host disease (GvHD) prophylaxis will include a calcineuron inhibitor [either tacrolimus (FK506) or cyclosporin A)], in combination with either methotrexate (MTX) or mycophenolate mofetil (MMF), all at doses as per the institutional protocols.
Part 2 Expansion AHSCT Procedure:
- Patients with hematological malignancies or myelodysplastic syndrome undergoing a first AHSCT procedure and who are in their 1st (CR1) or subsequent complete remission
- Type of allograft: Related or unrelated allogeneic hematopoietic stem cell transplant donors with no more than 1 HLA allele or antigen mismatch.
- Source of allograft: Unmodified (non-manipulated), bone marrow or mobilized peripheral blood stem cell transplant (PBSCT) using G-CSF as the mobilizing agent.
- Anti-graft versus host disease (GvHD) prophylaxis will include a calcineuron inhibitor [either tacrolimus (FK506) or cyclosporin A)], in combination with either methotrexate (MTX) or mycophenolate mofetil (MMF), all at doses as per the institutional protocols.
Exclusion Criteria:
- Female patients who are pregnant or lactating
- Patients about to undergo mini allogeneic transplant (also known as reduced intensity transplant, non-ablative or non-myeloablative transplant, or adoptive immunotherapy)
- Radiation, chemotherapy, immunotherapy in the previous 3 weeks, unrelated to the AHSCT procedure
- Patient who is about to undergo cord blood transplantation
- Procedures that are intended to deplete regulatory T-cells from donor transplant materials
- Known or suspected HIV infection
- Active hepatitis A, B, or C infection in recipient or donor
- Prior treatment with anti-thymocyte globulin, anti-CD20, or anti-CD3 antibodies
- Cardiac pacemaker or automatic implantable cardioverter-defibrillator
- Prior autologous or allogeneic hematopoietic stem cell transplantation
- Any other prior organ transplant
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01379209
Locations
| United States, California | |
| UCSD Moores Cancer Research Institute | Recruiting |
| San Diego, California, United States, 93093 | |
| Contact: Edward Ball, MD 858-822-6842 tball@ucsd.edu | |
| Principal Investigator: Edward (Ted) Ball, MD | |
| Stanford School of Medicine | Not yet recruiting |
| Stanford, California, United States, 94305 | |
| Contact: Robert Negrin, MD 650-723-0822 negrs@stanford.edu | |
| Contact: Laura Johnston, MD 650-723-0822 korb@stanford.edu | |
| Principal Investigator: Robert Negrin, MD | |
| Sub-Investigator: Laura Johnston, MD | |
| United States, Massachusetts | |
| Mass. General Hospital (Harvard - Dana Farber Partners) | Not yet recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: Yi-Bin Chen, MD 617-724-1124 YCHEN6@PARTNERS.ORG | |
| Principal Investigator: Yi-Bin Chen, MD | |
| United States, Ohio | |
| Ohio State University Comprehensive Cancer Center - The James | Recruiting |
| Columbus, Ohio, United States, 43210 | |
| Contact: Yvonne A Efebera, MD 614-293-2268 yvonne.efebera@osumc.edu | |
| Contact: Steven Devine, MD 614-293-5655 devine.54@osu.edu | |
| 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 pmartin@fhcrc.org | |
| Contact: Terry Furlong 206-667-5000 tfurlong@fhcrc.org | |
| Principal Investigator: Paul Martin, MD | |
Sponsors and Collaborators
Regimmune Inc.
Pacific-Link Regulatory Consulting LLC
More Information
Additional Information:
No publications provided
| Responsible Party: | Regimmune Inc. |
| ClinicalTrials.gov Identifier: | NCT01379209 History of Changes |
| Other Study ID Numbers: | RGI-2001-02 |
| Study First Received: | June 17, 2011 |
| Last Updated: | January 13, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Regimmune Inc.:
|
AHSCT Bone Marrow Transplant Leukemia myelodysplastic syndrome hematological malignancies |
Graft-versus-host-disease GvHD Hematopoietic Stem Cell Transplantation Stem Cell Transplantation |
Additional relevant MeSH terms:
|
Neoplasms Hematologic Neoplasms Neoplasms by Site Hematologic Diseases |
ClinicalTrials.gov processed this record on May 16, 2013