Glucocorticosteroid Refractory Acute GVHDPhase 2NCT01757197
Phase II Study of Tocilizumab for Patients With Glucocorticoid-refractory Acute GVHD After Allogeneic Hematopoetic Stem Cell Transplant (HSCT)
A Phase 2 study testing Toclizumab in people with Glucocorticosteroid Refractory Acute GVHD, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
The purpose of this study is to determine if Tocilizumab is a safe and effective treatment for steroid-refractory acute graft versus host disease. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Glucocorticosteroid Refractory Acute GVHD
- What is being tested?
- Toclizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Nov 2013to 17 Jun 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women ≥ 18 and ≤ 80 years of age
- Karnofsky Performance Status Scale ≥ 50%
- Glucocorticosteroid refractory acute GVHD Grade 2-4 by the Glucksberg functional classification.
- Patients who had experienced aGVHD grade 2-4 and responded to glucocorticosteroids in the past then had a flare of aGVHD requiring increasing immune suppression to 1 mg/kg of prednisone or equivalent are eligible for this study if they are refractory to steroids and provided that they did not receive a second line therapy for aGVHD in the past.
- Glucocorticosteroid refractory GVHD is defined as the following:
- No response to corticosteroid therapy at ≥ 1.0 mg/kg methylprednisolone or equivalent after the onset of acute GVHD for a minimum of 3 and a maximum of 7 days OR
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- Progression of at least 1 overall grade within 3 days of glucocorticosteroid use OR
- Incomplete response by 14 days of glucocorticosteroid use
- Ability to comply with planned procedures
- Ability to understand the information provided and to provide written evidence of informed consent
- Willingness of females of childbearing potential to use adequate contraception.
- Post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months prior to screening
Who cannot join
- Subjects with only grade 1 acute GVHD
- Concurrent medical condition or disease that may interfere with clinical trial participation
- Relapsed or persistent malignancy.
- Receiving other drugs for the treatment of glucocorticosteroid refractory GVHD.
- Severe hepatic veno-occlusive disease or sinusoidal obstruction syndrome.
- History of hypersensitivity or severe allergic reactions to humanized or murine monoclonal antibodies
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- Receipt of any experimental, unregistered therapy within or outside a clinical trial within 30 days or 5 plasma half-lives (whichever is shorter) before dosing
- Planned or current participation in any other clinical trial for treatment of GVHD during this clinical trial. Subjects are permitted on this trial if 30 days (or 5 half-lives) have passed since enrollment on other investigational drugs. If a subject develops another condition, he/she is permitted on other clinical trials to treat that condition. Subjects are not permitted to go on other clinical trials for steroid refractory acute GVHD. Subjects are permitted to participate in trials for chronic GVHD.
- Pregnancy (a negative serum or urine pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation.
- Pre-existing or recent onset of demyelinating disorders
- Pre-existing or recent onset of gastrointestinal perforation
- Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
- Receipt of a live vaccine within 4 weeks prior to first infusion
- Previous treatment with Natalizumab (Tysabri®)
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- Known active UNCONTROLLED bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds).
- Concomitant malignancies.
- History of psychiatric disorder that would interfere with normal participation in this protocol
- Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
- ANC < 0.5 x 103
- History of drug, alcohol, or chemical abuse within 6 months prior to screening
- Serum creatinine > 1.9 mg/dL (168 µmol/L). Patients with serum creatinine values exceeding limits may be eligible for the study if their estimated glomerular filtration rates (GFR) are >30
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times upper limit of normal (ULN) unless liver GVHD is suspected
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
Trial locations and contacts
1 site in 1 country.
United States1 site
Weill Cornell Medical College
New York, New York, 10021
About this study
Official title: Tocilizumab (an Anti-human IL-6 Receptor Monoclonal Antibody) as a First Line Therapy for Patients With Glucocorticoid-refractory Acute Graft vs. Host Disease (aGVHD) After Allogeneic Hematopoetic Stem Cell Transplant (HSCT), a Phase II Study.
The purpose of this study is to determine if Tocilizumab is a safe and effective treatment for steroid-refractory acute graft versus host disease.
Read the detailed description
This clinical trial is testing a drug called Tocilizumab (a monoclonal antibody) as a first line therapy for subjects with steroid-refractory acute graft versus host disease (acute GVHD) after undergoing a bone marrow transplant. The purpose of the study is to test the safety and efficacy of Tocilizumab at differing dose schedules. There are 2 phases to this study. Both phases include subjects with acute GVHD have not responded to steroid treatment. Subjects enrolled in Phase IIp will receive Tocilizumab 8 mg/kg every week or every 2 weeks. Subjects enrolled in Phase II will receive one of two dose schedules determined by the results of Phase IIp. Depending on the dose they are assigned to, subjects will receive Tocilizumab every week or every 2 weeks for a total of 8 doses. The study medication may be interrupted, withheld or stopped for different reasons. However, subjects will be asked to follow up periodically for one year after starting Tocilizumab treatment.
- Being tested
- Toclizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToclizumabDrug
Also called ACTEMRA®
8 mg/kg IV, once every 1-2 weeks. The maximum dose per infusion should not exceed 800 mg.
| Study group | Role | What they receive |
|---|---|---|
| All Patients | Experimental | Toclizumab will be administered on Day 0. The administration of tocilizumab will be every 2 weeks for a total of 8 doses. Receives: Drug: Toclizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With GVHD Who Are Tolerable to Tocilizumab After Having Failed Response to Glucocorticosteroid Treatment
Both subjects enrolled on this study experienced failed response to glucocorticosteroid treatment but were able to tolerate tocilizumab. We were unable to collect extensive data on these 2 subjects because they both died early on in the study due to disease complications.
Measured: Day 28
Secondary outcomes (3)
Disease-free Overall Survival at 100 Days, 6 Months and One Year From the Time of the First Tocilizumab Infusion.
We were unable to evaluate disease-free survival at 100 days, 6 months and one year from the time of the first tocilizumab infusion. All subjects enrolled on this study died before this time point and the study closed to enrollment due to slow accrual.
Measured: Approximately 1 year
Toclizumab Response in Each Organ
We were unable to assess the Tocilizumab response in each organ at 1 year. All subjects enrolled on this study died before this time point and the study closed to enrollment due to slow accrual.
Measured: 1 year
Effect of Toclizumab on Karnofsky Performance Status
We were unable to evaluate the effect of tocilizumab on Karnofsky Performance Status at 1 year. All subjects enrolled on this study died before this time point and the study closed to enrollment due to slow accrual.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2012 (estimated)
- Study start7 Nov 2013
- Primary completion17 Jun 2014
- Study completion17 Jun 2014
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Glucocorticosteroid Refractory Acute GVHDStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Usama Gergis, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01757197
- Sponsor's protocol ID
- 1202012180
- Other IDs
- ML28046
- Status last verified
- May 2018
- First submitted
- 13 Dec 2012
- Last updated
- 11 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tocilizumab (an Anti-human IL-6 Receptor Monoclonal Antibody) as a First Line Therapy for Patients With Glucocorticoid-refractory Acute Graft vs. Host Disease (aGVHD) After Allogeneic Hematopoetic Stem Cell Transplant (HSCT), a Phase II Study.
- ClinicalTrials.gov ID
- NCT01757197
- Acronym / sponsor ID
- 1202012180
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Study start
- 7 Nov 2013 (actual)
- Primary completion
- 17 Jun 2014 (actual)
- Study completion
- 17 Jun 2014 (actual)
- First posted
- 28 Dec 2012 (estimated)
- Results
- Posted 5 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if Tocilizumab is a safe and effective treatment for steroid-refractory acute graft versus host disease.
Detailed description
This clinical trial is testing a drug called Tocilizumab (a monoclonal antibody) as a first line therapy for subjects with steroid-refractory acute graft versus host disease (acute GVHD) after undergoing a bone marrow transplant. The purpose of the study is to test the safety and efficacy of Tocilizumab at differing dose schedules. There are 2 phases to this study. Both phases include subjects with acute GVHD have not responded to steroid treatment. Subjects enrolled in Phase IIp will receive Tocilizumab 8 mg/kg every week or every 2 weeks. Subjects enrolled in Phase II will receive one of two dose schedules determined by the results of Phase IIp. Depending on the dose they are assigned to, subjects will receive Tocilizumab every week or every 2 weeks for a total of 8 doses. The study medication may be interrupted, withheld or stopped for different reasons. However, subjects will be asked to follow up periodically for one year after starting Tocilizumab treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Patients | Experimental | Drug: ToclizumabToclizumab will be administered on Day 0. The administration of tocilizumab will be every 2 weeks for a total of 8 doses. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Men or women ≥ 18 and ≤ 80 years of age
- Karnofsky Performance Status Scale ≥ 50%
- Glucocorticosteroid refractory acute GVHD Grade 2-4 by the Glucksberg functional classification.
- Patients who had experienced aGVHD grade 2-4 and responded to glucocorticosteroids in the past then had a flare of aGVHD requiring increasing immune suppression to 1 mg/kg of prednisone or equivalent are eligible for this study if they are refractory to steroids and provided that they did not receive a second line therapy for aGVHD in the past.
- Glucocorticosteroid refractory GVHD is defined as the following:
Key exclusion criteria (24 listed)
- Subjects with only grade 1 acute GVHD
- Concurrent medical condition or disease that may interfere with clinical trial participation
- Relapsed or persistent malignancy.
- Receiving other drugs for the treatment of glucocorticosteroid refractory GVHD.
- Severe hepatic veno-occlusive disease or sinusoidal obstruction syndrome.
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 |
|---|---|---|
| ToclizumabAlso: ACTEMRA®8 mg/kg IV, once every 1-2 weeks. The maximum dose per infusion should not exceed 800 mg. | Drug | All Patients |
Primary outcome
Number of Subjects With GVHD Who Are Tolerable to Tocilizumab After Having Failed Response to Glucocorticosteroid Treatment
Time frame: Day 28
Both subjects enrolled on this study experienced failed response to glucocorticosteroid treatment but were able to tolerate tocilizumab. We were unable to collect extensive data on these 2 subjects because they both died early on in the study due to disease complications.
3 secondary outcomes
Disease-free Overall Survival at 100 Days, 6 Months and One Year From the Time of the First Tocilizumab Infusion.
Time frame: Approximately 1 year
Toclizumab Response in Each Organ
Time frame: 1 year
Effect of Toclizumab on Karnofsky Performance Status
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Usama Gergis, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toclizumab in people with Glucocorticosteroid Refractory Acute GVHD, run by Weill Medical College of Cornell University at 1 site 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 12 inclusion and 24 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: stopped early, as of the sponsor's last update on 11 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 5 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects With GVHD Who Are Tolerable to Tocilizumab After Having Failed Response to Glucocorticosteroid Treatment (time frame: Day 28). 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 11 Jun 2018.