Steroid-refractory aGvHD Subsequent to Allogeneic Hematopoietic Cell TransplantationPhase 2NCT02694770
A Study Evaluating the Efficacy and Safety of Neihulizumab vs "Conventional Treatment" to Treat Sr-aGvHD
A Phase 2 study testing Neihulizumab Treatment and Conventional Treatment in people with Steroid-refractory aGvHD Subsequent to Allogeneic Hematopoietic Cell Transplantation, run by AbGenomics B.V Taiwan Branch at 2 sites in United States.
Trial summary
This study is to assess the efficacy of Neihulizumab versus "conventional therapy" and to evaluate safety, pharmacokinetics and immunogenicity in treating steroid-refractory acute Graft-vs-Host Disease Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Steroid-refractory aGvHD Subsequent to Allogeneic Hematopoietic Cell Transplantation
- What is being tested?
- Neihulizumab Treatment and Conventional Treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2016to Feb 2018
- Phase
- Phase 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
- Patient must be ≥18years of age, males or females;
- Patient must have been recipients of a single allogeneic HCT; bone marrow, peripheral blood and/or umbilical cord blood recipients are allowed
- Patients must have aGvHD without feature of classic chronic GvHD or overlap GvHD;
- Patients must have received no prior treatment for aGvHD other than steroids;
- Patients must have biopsy proven grade II to IV aGvHD progressing after at least 3 days, non-improving grade III to IV aGvHD persistent after at least 7 days, or non-improving grade II aGvHD persistent after at least 14 days of methylprednisolone 2mg/kg/day or equivalent; Patients with initial response but have flare of aGvHD within 14 days with methylprednisolone > 0.5 mg/kg/day or equivalent are also eligible;
- Patient must have an ANC of > 500/mm3 and no evidence of HCT graft failure or multi-organ failure;
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- Patient must have Karnofsky Performance Status (KPS) ≥50%;
- Patient must give informed consent and sign an approved consent form prior to any study procedures;
- Females of childbearing potential must have a negative pregnancy test result prior to enrollment. Males and females of childbearing potential must agree to use a highly effective method of birth control during the study.
Who cannot join
- Uncontrolled infections not responsive to antimicrobial therapy or requiring intensive critical care or vasopressors;
- Evidence of end-organ infection due to CMV;
- HIV infection or a known HIV-related malignancy (NOTE: patients positive for hepatitis B or hepatitis C are not excluded, and may be evaluated on a case by case basis).
- Tuberculosis, history of tuberculosis or a known positive Quantiferon test for tuberculosis
- Donor lymphocyte infusion for residual or relapsed disease or mixed chimerism. DLI as part of the planned HCT protocol are allowed
- Relapsed disease after transplant or progressive malignant disease, including post-transplant lymphoproliferative disease; any secondary malignancy diagnosed since HCT
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- Renal failure requiring hemodialysis
- Need ICU care, with life expectancy of less than 28 days, with ongoing or unresolved veno-occlusive disease, with unstable hemodynamics, with evidence of current or previous clinically significant disease, medical condition or finding of the medical examination (including vital signs and ECG), that in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data
- History of allergy/hypersensitivity to a systemically administered biologic agent or its excipients
- Pregnant or nursing
Trial locations and contacts
2 sites in 1 country.
United States2 sites
MD Anderson Cancer Center
Houston, Texas, 77030
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
About this study
Official title: A Phase II Study of Neihulizumab vs "Conventional Treatment" to Treat Steroid-refractory Acute Graft-vs-host Disease (Sr-aGvHD) in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation
This study is to assess the efficacy of Neihulizumab versus "conventional therapy" and to evaluate safety, pharmacokinetics and immunogenicity in treating steroid-refractory acute Graft-vs-Host Disease
Read the detailed description
This current Phase II trial is a randomized, open label, controlled, multiple dose, multi-centre study to study the clinical efficacy and safety of Neihulizumab vs "Conventional Treatment" to treat steroid-refractory acute graft-vs-host disease (sr-aGvHD) in patients undergoing allogeneic hematopoietic cell transplantation.
This study will enroll a minimum of 90 patients, approximately 60 in Neihulizumab treatment arm and 30 in Conventional treatment control arm.
The primary objectives is to evaluate the efficacy of Neihulizumab treatment in patients with steroid-refractory acute GvHD compared to "conventional treatment." The secondary objectives are to investigate safety, pharmacokinetics, and immunogenicity of Neihulizumab administration in subjects with steroid-refractory acute GvHD.
For safety evaluation, the parameters to be assessed are adverse events (AEs), discontinuation of therapy due to AEs, safety laboratory analysis, ECG, vital signs, physical examination, and immunogenicity.
- Being tested
- Neihulizumab Treatment, Conventional Treatment
- Keywords
- aGvHD, GvHD, sr-aGvHD, biologics, monoclonal antibody
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neihulizumab TreatmentBiological
Also called AbGn-168H
Monoclonal antibody
Conventional TreatmentBiological
2nd line therapy for aGvHD at the discretion of attending physician, including but not limited to biologics such as ATG, TNF-alpha inhibitors, pentostatin, sirolimus, mycophenolate mofetil and extracorporeal photopheresis.
| Study group | Role | What they receive |
|---|---|---|
| Neihulizumab | Experimental | Patients will receive a total of 4 doses of Neihulizumab (AbGn-168H) on Day 1 (Week 0), Day 8 (Week 1), Day 15 (Week 2), and Day 22 (Week 3) by 1-hour i.v. infusion. Receives: Biological: Neihulizumab Treatment |
| "Conventional Treatment" | Active comparator | Patients will receive a 2nd line therapy for aGvHD at the discretion of attending physician according to the standard practice at the study center. Currently there is no treatment for sr-aGvHD is approved in USA or Europe. There is no Standard treatment of this disease is recommended by American Society for Blood and Marrow Transplantation (ASBMT). Therefore, the study is designed to allow any established institutional practice for off-label use of a commercially available product for patients in the Conventional Treatment arm. Patients in this arm may receive treatments provided in ASBMT guidance such as ATG, TNF-alpha inhibitors (such as Etanercept and infliximab), pentostatin, sirolimus, mycophenolate mofetil and extracorporeal photopheresis, methotrexate, basiliximab, daclizumab, inolimomab, denileukin diftitox, alemtuzumab, ATG+ etanercept, Dacliz + etanercept, Dacliz+ infliximab, and Dacliz/inflix/horse ATG. Receives: Biological: Conventional Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (Complete Response+Partial Response)
Measured: Day 28 after the initiation of sr-aGvHD treatment
Secondary outcomes (6)
Overall response rate (Complete Response+Partial Response)
Measured: Day 56 after the initiation of sr-aGvHD treatment
Complete Response+Very Good Partial Response
Measured: Day 28 and Day 56 after the initiation of sr-aGvHD treatment
Overall survival
Measured: Day 180 after the initiation of sr-aGvHD treatment
Cumulative steroid dose
Measured: Day 28 after the initiation of sr-aGvHD treatment
Cumulative incidence of chronic GvHD
Measured: Day 180 after the initiation of sr-aGvHD treatment
Cumulative incidence of primary disease relapse
Measured: Day 180 after the initiation of sr-aGvHD treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2016 (estimated)
- Study startJul 2016
- Primary completionSep 2017 (estimated)
- Study completionFeb 2018 (estimated)
Why it stopped: corporate decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Steroid-refractory aGvHD Subsequent to Allogeneic Hematopoietic Cell TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbGenomics B.V Taiwan Branch
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shih-Yao Lin, MD, PhD, Study chair, AbGenomics B.V.Paul Martin (Lead), MD, Principal investigator, Fred Hutchinson Cancer CenterMarco Mielcarek (Co-Lead), MD, Principal investigator, Fred Hutchinson Cancer CenterAmin Alousi (Co-Lead), MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02694770
- Sponsor's protocol ID
- 2015.011.01
- Status last verified
- Apr 2016
- First submitted
- 18 Feb 2016
- Last updated
- 25 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Neihulizumab vs "Conventional Treatment" to Treat Steroid-refractory Acute Graft-vs-host Disease (Sr-aGvHD) in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT02694770
- Acronym / sponsor ID
- 2015.011.01
- Keywords
- aGvHD, GvHD, sr-aGvHD, biologics, monoclonal antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: corporate decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AbGenomics B.V Taiwan BranchIndustry (pharma, biotech, devices)
- Study start
- Jul 2016
- Primary completion
- Sep 2017 (estimated)
- Study completion
- Feb 2018 (estimated)
- First posted
- 1 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to assess the efficacy of Neihulizumab versus "conventional therapy" and to evaluate safety, pharmacokinetics and immunogenicity in treating steroid-refractory acute Graft-vs-Host Disease
Detailed description
This current Phase II trial is a randomized, open label, controlled, multiple dose, multi-centre study to study the clinical efficacy and safety of Neihulizumab vs "Conventional Treatment" to treat steroid-refractory acute graft-vs-host disease (sr-aGvHD) in patients undergoing allogeneic hematopoietic cell transplantation.
This study will enroll a minimum of 90 patients, approximately 60 in Neihulizumab treatment arm and 30 in Conventional treatment control arm.
The primary objectives is to evaluate the efficacy of Neihulizumab treatment in patients with steroid-refractory acute GvHD compared to "conventional treatment." The secondary objectives are to investigate safety, pharmacokinetics, and immunogenicity of Neihulizumab administration in subjects with steroid-refractory acute GvHD.
For safety evaluation, the parameters to be assessed are adverse events (AEs), discontinuation of therapy due to AEs, safety laboratory analysis, ECG, vital signs, physical examination, and immunogenicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neihulizumab | Experimental | Biological: Neihulizumab TreatmentPatients will receive a total of 4 doses of Neihulizumab (AbGn-168H) on Day 1 (Week 0), Day 8 (Week 1), Day 15 (Week 2), and Day 22 (Week 3) by 1-hour i.v. infusion. |
| "Conventional Treatment" | Active comparator | Biological: Conventional TreatmentPatients will receive a 2nd line therapy for aGvHD at the discretion of attending physician according to the standard practice at the study center. Currently there is no treatment for sr-aGvHD is approved in USA or Europe. There is no Standard treatment of this disease is recommended by American Society for Blood and Marrow Transplantation (ASBMT). Therefore, the study is designed to allow any established institutional practice for off-label use of a commercially available product for patients in the Conventional Treatment arm. Patients in this arm may receive treatments provided in ASBMT guidance such as ATG, TNF-alpha inhibitors (such as Etanercept and infliximab), pentostatin, sirolimus, mycophenolate mofetil and extracorporeal photopheresis, methotrexate, basiliximab, daclizumab, inolimomab, denileukin diftitox, alemtuzumab, ATG+ etanercept, Dacliz + etanercept, Dacliz+ infliximab, and Dacliz/inflix/horse ATG. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patient must be ≥18years of age, males or females;
- Patient must have been recipients of a single allogeneic HCT; bone marrow, peripheral blood and/or umbilical cord blood recipients are allowed
- Patients must have aGvHD without feature of classic chronic GvHD or overlap GvHD;
- Patients must have received no prior treatment for aGvHD other than steroids;
- Patients must have biopsy proven grade II to IV aGvHD progressing after at least 3 days, non-improving grade III to IV aGvHD persistent after at least 7 days, or non-improving grade II aGvHD persistent after at least 14 days of methylprednisolone 2mg/kg/day or equivalent; Patients with initial response but have flare of aGvHD within 14 days with methylprednisolone > 0.5 mg/kg/day or equivalent are also eligible;
Key exclusion criteria (10 listed)
- Uncontrolled infections not responsive to antimicrobial therapy or requiring intensive critical care or vasopressors;
- Evidence of end-organ infection due to CMV;
- HIV infection or a known HIV-related malignancy (NOTE: patients positive for hepatitis B or hepatitis C are not excluded, and may be evaluated on a case by case basis).
- Tuberculosis, history of tuberculosis or a known positive Quantiferon test for tuberculosis
- Donor lymphocyte infusion for residual or relapsed disease or mixed chimerism. DLI as part of the planned HCT protocol are allowed
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neihulizumab TreatmentAlso: AbGn-168HMonoclonal antibody | Biological | Neihulizumab |
| Conventional Treatment2nd line therapy for aGvHD at the discretion of attending physician, including but not limited to biologics such as ATG, TNF-alpha inhibitors, pentostatin, sirolimus, mycophenolate mofetil and extracorporeal photopheresis. | Biological | "Conventional Treatment" |
Primary outcome
Overall response rate (Complete Response+Partial Response)
Time frame: Day 28 after the initiation of sr-aGvHD treatment
6 secondary outcomes
Overall response rate (Complete Response+Partial Response)
Time frame: Day 56 after the initiation of sr-aGvHD treatment
Complete Response+Very Good Partial Response
Time frame: Day 28 and Day 56 after the initiation of sr-aGvHD treatment
Overall survival
Time frame: Day 180 after the initiation of sr-aGvHD treatment
Cumulative steroid dose
Time frame: Day 28 after the initiation of sr-aGvHD treatment
Cumulative incidence of chronic GvHD
Time frame: Day 180 after the initiation of sr-aGvHD treatment
Cumulative incidence of primary disease relapse
Time frame: Day 180 after the initiation of sr-aGvHD treatment
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2016.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shih-Yao Lin, MD, PhD study chair
AbGenomics B.V.
Paul Martin (Lead), MD principal investigator
Fred Hutchinson Cancer Center
Marco Mielcarek (Co-Lead), MD principal investigator
Fred Hutchinson Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neihulizumab Treatment and Conventional Treatment in people with Steroid-refractory aGvHD Subsequent to Allogeneic Hematopoietic Cell Transplantation, run by AbGenomics B.V Taiwan Branch at 2 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 9 inclusion and 10 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: withdrawn, as of the sponsor's last update on 25 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 phase mean?
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 was withdrawn before enrolling participants, so there are no results.
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?
Overall response rate (Complete Response+Partial Response) (time frame: Day 28 after the initiation of sr-aGvHD treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Apr 2016.