Intravenous Administration of RGI-2001 in Patient Undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT)

NCT01379209 | Completed Phase 1 DMC

• 1 other identifier: RGI-2001-02
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 6

Brief Summary

The clinical trial is a Phase 1/2a, open-label, multi-center, dose-escalation study to evaluate the safety, tolerability and pharmacokinetic profile of RGI-2001 in patients undergoing AHSCT, with radiation or non-radiation myeloablative preparative treatment. The study will be separated into two parts; a dose escalation phase to assess safety, followed by a large expansion phase to further evaluate the pharmacologic effects of either a Maximum Tolerated Dose, Maximum Feasible Dose or optimal pharmacologically active dose of RGI-2001. The initial dose escalation safety portion of the study (Part 1) will include higher risk patients and limit the unrelated donor transplants. After safety is established in part 1 of the study, the second portion of the study will expand the enrollment criteria and allow transplantation by either related or unrelated donors. This study will endeavor to identify the dose range at which RGI-2001 has an acceptable safety profile, at which biologic activity is observed, and to guide possible dose levels to utilize in later phase studies based on biological activity.

Conditions

Graft Versus Host Disease

Keywords

AHSCT; Bone Marrow Transplant; Leukemia; myelodysplastic syndrome; hematological malignancies; Graft-versus-host-disease; GvHD; Hematopoietic Stem Cell Transplantation; Stem Cell; Transplantation

Outcome Measures

Primary Outcomes (1)

• The maximum tolerated dose (MTD) or maximum feasible dose (MFD) of RGI-2001

  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

  By day 29

Secondary Outcomes (4)

• Pharmacodynamic Effects

  Within 100 days from AHSCT

• Pharmacokinetics of RGI-2001

  Within first 8 days

• Efficacy in reducing the intensity of GvHD

  Within the first 100 days after AHSCT

• Optimal Dose of RGI-2001

  Within first 100 days after AHSCT

Study Arms (8)

RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis

EXPERIMENTAL

RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Dose escalation cohort 1 in part 1 of this study will include 2-6 patients

Drug: RGI-2001; Drug: Calcineurin Inhibitors; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Conditioning Regimen; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Methotrexate; Drug: Mofetil Mycophenolate; Drug: sirolimus

RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis

EXPERIMENTAL

RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 2 in part 1 of this study will include 2-6 patients

Drug: RGI-2001; Drug: Calcineurin Inhibitors; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Conditioning Regimen; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Methotrexate; Drug: Mofetil Mycophenolate; Drug: sirolimus

RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis

EXPERIMENTAL

RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 3 in part 1 of this study will include 2-6 patients

Drug: RGI-2001; Drug: Calcineurin Inhibitors; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Conditioning Regimen; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Methotrexate; Drug: Mofetil Mycophenolate; Drug: sirolimus

RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis

EXPERIMENTAL

RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 4 in part 1 of this study will include 2-6 patients

Drug: RGI-2001; Drug: Calcineurin Inhibitors; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Conditioning Regimen; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Methotrexate; Drug: Mofetil Mycophenolate; Drug: sirolimus

RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis

EXPERIMENTAL

RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 5 in part 1 of this study will include 2-6 patients

Drug: RGI-2001; Drug: Calcineurin Inhibitors; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Conditioning Regimen; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Methotrexate; Drug: Mofetil Mycophenolate; Drug: sirolimus

RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis

EXPERIMENTAL

RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 6 in part 1 of this study will include 2-6 patients

Drug: RGI-2001; Drug: Calcineurin Inhibitors; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Conditioning Regimen; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Methotrexate; Drug: Mofetil Mycophenolate; Drug: sirolimus

RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis

EXPERIMENTAL

RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols Cohort 7 in part 1 of this study will include 2-6 patients (optional)

Drug: RGI-2001; Drug: Calcineurin Inhibitors; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Conditioning Regimen; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Methotrexate; Drug: Mofetil Mycophenolate; Drug: sirolimus

RGI-2001 + Standard of Care GVHD Prophylaxis

EXPERIMENTAL

RGI-2001 will be add to standard treatment with a calcineurin inhibitor, in combination with either methotrexate, mycophenolate mofetil, or sirolimus all at doses as per the institutional protocols 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; Drug: Calcineurin Inhibitors; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Conditioning Regimen; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Methotrexate; Drug: Mofetil Mycophenolate; Drug: sirolimus

Interventions

RGI-2001 DRUG

A single administration of RGI-2001 on Day 0 post AHSCT.

Also known as: KRN-7000, RGI-7000

RGI-2001 + Standard of Care GVHD Prophylaxis; RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis

Calcineurin Inhibitors DRUG

GVHD prophylaxis according to institutional guidelines. Subjects could have received any number/combinations of treatments.

RGI-2001 + Standard of Care GVHD Prophylaxis; RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

According to institutional guidelines.

RGI-2001 + Standard of Care GVHD Prophylaxis; RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis

Conditioning Regimen DRUG

Myeloablative preparative treatment according to institutional guidelines. Subjects could have received any number/combinations of treatments.

RGI-2001 + Standard of Care GVHD Prophylaxis; RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis

Allogeneic Bone Marrow Transplantation PROCEDURE

According to institutional guidelines

RGI-2001 + Standard of Care GVHD Prophylaxis; RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis

Methotrexate DRUG

Also known as: Administered for GVHD prophylaxis as per institutional guidelines

RGI-2001 + Standard of Care GVHD Prophylaxis; RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis

Mofetil Mycophenolate DRUG

Also known as: Administered for GVHD prophylaxis as per institution guidelines

RGI-2001 + Standard of Care GVHD Prophylaxis; RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis

sirolimus DRUG

Administered for GVHD prophylaxis as per institutional guidelines

RGI-2001 + Standard of Care GVHD Prophylaxis; RGI-2001 0.001 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.01 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 0.1 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 1.0 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 10 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 100 μg/kg + Standard of Care GVHD Prophylaxis; RGI-2001 250μg/kg + Standard of Care GVHD Prophylaxis

Eligibility Criteria

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

You may qualify if:

• Subject has a hematological malignancy or aplastic anemia (AA) and is undergoing a first allogeneic transplant procedure.
• Meet one of the following underlying disease criteria:
• a. Acute myelogenous leukemia (AML) i. First or subsequent morphologic remission b. Acute lymphoblastic leukemia (ALL) i. First or subsequent morphologic remission c. Chronic myelogenous leukemia (CML) i. Chronic phase; or ii. Accelerated phase d. Multiple Myeloma (MM) i. Not more than 20% plasma cells in the bone marrow e. Myelodysplastic syndrome (MDS), including chronic myelomonocytic leukemia (CMML), who have received at least one previous induction regimen and have \<10% blasts f. Myeloproliferative disorder (MPD), including; i. myeloid metaplasia, and ii. myelofibrosis g. Non-Hodgkin's Lymphoma (NHL) i. High-risk NHL in first remission; or ii. Relapsed or refractory NHL h. Hodgkin's lymphoma (HL) beyond first remission i. Aplastic anemia (AA)
• Male or female, age ≥18 years of age
• Reasonable expectation of survival for at least 3 months, if the transplant procedure is successful
• Eastern Cooperative Oncology Group (ECOG) status of 0-2 or Karnofsky Performance Status (KPS) of \> 60
• Transplant Donor
• Part 1 (Phase 1: Dose Escalation Phase):
• Unrelated transplant donor with no more than 1 HLA allele or antigen mismatch, defined as loci A, B, C and DR (note: DQ is excluded)
• Part 2 (Phase 2a: Expansion Phase):Related or unrelated transplant donor, with no more than 1 HLA allele or antigen mismatch, defined as loci A, B, C and DR (note: DQ is excluded).
• Source of the allograft
• Part 1 (Phase 1: Dose Escalation Phase):Unmodified (non-manipulated) bone marrow, or mobilized peripheral blood stem cell (PBSC) transplant, using G-CSF as the mobilizing agent.
• Part 2: (Phase 2a: Expansion Phase) Unmodified (non-manipulated) bone marrow, or mobilized peripheral blood stem cell (PBSC) transplant, using G-CSF as the mobilizing agent.
• Anti-graft-versus-host disease (GvHD) prophylaxis:
• A calcineurin inhibitor \[either tacrolimus (FK506) or cyclosporin A)\], in combination with either methotrexate (MTX), mycophenolate mofetil (MMF) or sirolimus (RAPA) all at doses as per the institutional protocols

You may not qualify if:

• Female subjects who are pregnant or lactating
• Subjects about to undergo a non-ablative or non-myeloablative transplant
• AML or ALL patient who are in relapse (\>5% blasts) or who are defined as primary refractory
• Blast crisis CML
• Radiation, chemotherapy, immunotherapy in the previous 3 weeks, unrelated to the transplant procedure
• Subjects who, in the judgment of the Investigator have not recovered from the effects of previous therapy
• Subject 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
• Uncontrolled active infection requiring IV antibiotics in recipient or donor
• Major surgery within 1 month before Day 0
• Participation in an investigational study within 1 month prior to Day 0
• Prior treatment with anti-CD3 antibodies
• Treatment with anti-CD20 antibodies or anti-thymocyte globulin (ATG) within 3 months of the AHSCT procedure (i.e. infusion of transplant material and RGI-2001).

Sponsors & Collaborators

• Regimmune Corporation: lead

Study Sites (6)

UCSD Moores Cancer Research Institute

San Diego, California, 93093, United States

Location

Stanford School of Medicine

Stanford, California, 94305, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Ohio State University Comprehensive Cancer Center - The James

Columbus, Ohio, 43210, United States

Location

Methodist Healthcare System

San Antonio, Texas, 78229, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Links

• Regimmune Company Website
• Fred Hutchinson Cancer Research Center
• Stanford School of Medicine
• UCSD Moores Cancer Center
• OSU The James Comprehensive Cancer Center

MeSH Terms

Conditions

Graft vs Host Disease; Leukemia; Myelodysplastic Syndromes; Hematologic Neoplasms

Interventions

KRN 7000; Calcineurin Inhibitors; Transplantation Conditioning; Methotrexate; Mycophenolic Acid; Sirolimus

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2011
• First Posted: June 23, 2011
• Study Start: September 1, 2011
• Primary Completion: June 1, 2015
• Study Completion: April 1, 2017
• Last Updated: October 23, 2019

Record last verified: 2019-09

Locations

US (6)