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Graft Versus Host DiseasePhase 1/2NCT01379209

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

A Phase 1/2 study testing RGI-2001, Calcineurin Inhibitors and Allogeneic Hematopoietic Stem Cell Transplantation in people with Graft Versus Host Disease, run by Regimmune Corporation at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft Versus Host Disease
What is being tested?
RGI-2001, Calcineurin Inhibitors and Allogeneic Hematopoietic Stem Cell Transplantation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
6 sitesUnited States
Study dates
Sep 2011to Apr 2017
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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
Show all 24Show fewer
  • 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
  • Adequate hepatic function, with bilirubin not exceeding the upper limit of normal (except when attributed to Gilbert's Disease), and AST and ALT of less than 1.5 times the upper limit of normal
  • No clinically significant cardiac conduction disorder on screening ECG
  • Serum creatinine ≤ 2.0 mg/dL
  • Female patients of childbearing potential must have a negative serum pregnancy test prior to enrollment and must agree to use dual method of contraception for 30 days after study drug administration. Approved methods of contraception include, an IUD with spermicide, a female condom with spermicide, a diaphragm with spermicide, a cervical cap with spermicide, use of a condom with spermicide by sexual partner or a sterile sexual partner.
  • If male, subjects must be sterile or willing to use an approved method of contraception from the time of Informed Consent to 30 days after study drug treatment. Males must be willing to refrain from sperm donation within 30 days after study drug treatment.
  • No clinically significant acute or chronic medical condition that in the opinion of the investigator will interfere with study participation
  • No clinically significant laboratory abnormalities as determined by the Principal Investigator, in consultation with the Sponsor's Medical Monitor
  • No active infection
  • Have signed written informed consent before undergoing any study related procedures and is willing to comply with all study procedures

Who cannot join

  • 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
Show all 31Show fewer
  • 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).
  • Vaccination within the preceding 2 weeks prior to the planned dose of RGI-2001
  • Planned vaccination within 2 months after study drug administration
  • Known history of cardiac dysfunction (e.g. <50% ejection fraction), ischemia, conduction abnormalities, or myocardial infarction in the previous six months
  • Cardiac pacemaker or automatic implantable cardioverter-defibrillator
  • Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms
  • Congenital long QT syndrome or family history of long QT syndrome
  • History of additional risk factors for torsades de pointes (TdP) (e.g., heart failure, hypokalemia)
  • Bundle branch block
  • Connective tissue/rheumatologic disorders
  • History of autoimmune disease
  • History of solid tumor, excluding non-melanoma skin or cervical carcinoma after curative resection, within the preceding 5 years
  • Uncontrolled diabetes
  • Prior allogeneic hematopoietic stem cell transplantation
  • Any other prior organ transplant
  • Psychiatric or addictive disorders that preclude obtaining reliable informed consent
  • Any other condition that, in the opinion of the investigator, renders the subject unsuitable for study participation

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Ohio State University Comprehensive Cancer Center - The James

    Columbus, Ohio, 43210

  • Methodist Healthcare System

    San Antonio, Texas, 78229

  • UCSD Moores Cancer Research Institute

    San Diego, California, 93093

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Stanford School of Medicine

    Stanford, California, 94305

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 1/2a, Open-Label, Multicenter, Dose-Escalation Study to Evaluate the Safety and Tolerability of Intravenous Administration of RGI-2001 in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT)

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.

Read the detailed description

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.

In Part 1 (Phase 1: Dose Escalation Phase), patients will receive a single intravenous administration of RGI-2001 approximately 30 minutes after completion of the transplant (either allogeneic PBSCs or allogenic bone marrow transplantation (unmodified)) with the dosage based upon the assigned treatment cohort. Eligible patients will be enrolled in five to seven centers in the United States. Patients who are undergoing 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 six dose levels will be evaluated in Part 1, with an option for an additional cohort (Cohort 7) 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 who are undergoing either allogeneic PBSCs or allogenic bone marrow transplantation (unmodified) will be enrolled in Part 2 of the study.

Patients will be monitored for safety for 29 days after the transplant procedure.

All patients will be followed for 100 days following transplant procedure for the incidence of acute GvHD, according to the Modified Keystone Criteria for grading acute GvHD (Przepiorka D, et al)

Being tested
RGI-2001, Calcineurin Inhibitors, Allogeneic Hematopoietic Stem Cell Transplantation, Conditioning Regimen, Allogeneic Bone Marrow Transplantation
Keywords
AHSCT, Bone Marrow Transplant, Leukemia, myelodysplastic syndrome, hematological malignancies, Graft-versus-host-disease, GvHD, Hematopoietic Stem Cell Transplantation, Stem Cell, Transplantation
Medical subject headings
Graft vs Host Disease, Leukemia, Myelodysplastic Syndromes, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RGI-2001Drug

    Also called KRN-7000, RGI-7000

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

  • Calcineurin InhibitorsDrug

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

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    According to institutional guidelines.

  • Conditioning RegimenDrug

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

  • Allogeneic Bone Marrow TransplantationProcedure or surgery

    According to institutional guidelines

  • MethotrexateDrug

    Also called Administered for GVHD prophylaxis as per institutional guidelines

  • Mofetil MycophenolateDrug

    Also called Administered for GVHD prophylaxis as per institution guidelines

  • sirolimusDrug

    Administered for GVHD prophylaxis as per institutional guidelines

Study groups in NCT01379209
Study groupRoleWhat they receive
RGI-2001 0.001 μg/kg + Standard of Care GVHD ProphylaxisExperimentalRGI-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
Receives: 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 ProphylaxisExperimentalRGI-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
Receives: 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 ProphylaxisExperimentalRGI-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
Receives: 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 ProphylaxisExperimentalRGI-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
Receives: 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 ProphylaxisExperimentalRGI-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
Receives: 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 ProphylaxisExperimentalRGI-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
Receives: 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 ProphylaxisExperimentalRGI-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)
Receives: 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 ProphylaxisExperimentalRGI-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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: By day 29

Secondary outcomes (4)

  1. Pharmacodynamic Effects

    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.

    Measured: Within 100 days from AHSCT

  2. Pharmacokinetics of RGI-2001

    Obtain pharmacokinetic parameters such as Cmax, Cmin, Tmax, AUC and half-life of the study drug in plasma.

    Measured: Within first 8 days

  3. Efficacy in reducing the intensity of GvHD

    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.

    Measured: Within the first 100 days after AHSCT

  4. Optimal Dose of RGI-2001

    Determine optimal doses of RGI-2001 for further evaluation based on pharmacodynamic response and effectiveness in reducing the intensity of GvHD

    Measured: Within first 100 days after AHSCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionJun 2015
  4. Study completionApr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01379209
Sponsor's protocol ID
RGI-2001-02
Status last verified
Sep 2019
First submitted
17 Jun 2011
Last updated
23 Oct 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RGI-2001, Calcineurin Inhibitors and Allogeneic Hematopoietic Stem Cell Transplantation in people with Graft Versus Host Disease, run by Regimmune Corporation at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The maximum tolerated dose (MTD) or maximum feasible dose (MFD) of RGI-2001 (time frame: By day 29). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01379209.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2019.

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