Graft vs Host DiseasePhase 1/2NCT00409695
Thymoglobulin (ATG) Dose Finding Study
A Phase 1/2 study testing Low Dose Thymoglobulin (ATG) and High Dose Thymoglobulin (ATG) in people with Graft vs Host Disease, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Primary Objective: To determine the response and toxicity rate at day 56 of two different dose levels of thymoglobulin (ATG) [anti-thymocyte globulin (rabbit)] as a treatment of steroid-refractory acute graft versus host disease (aGVHD). Secondary Objectives: To evaluate the response rate at day 28. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Graft vs Host Disease
- What is being tested?
- Low Dose Thymoglobulin (ATG) and High Dose Thymoglobulin (ATG)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Aug 2007
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients who underwent their first allogeneic transplant for any malignancy and with any cell (bone marrow, peripheral stem cell, cord blood) or donor (matched or mismatched related or unrelated) source.
- Biopsy-proven, grade II-IV aGVHD following allogeneic hematopoietic stem cell transplantation (HSCT) of any source (bone marrow, peripheral blood or cord blood stem cells). Enrollment may be started prior to results of biopsy in cases of high clinical suspicion for aGVHD.
- Early steroid-refractory aGVHD. This is defined as any NR or PD after a minimum of 3 days and not more than 1 week of 1 mg/kg/day of methylprednisolone.
- Ability to sign informed consent.
- Ability to return for clinical follow-up as specified in the protocol.
- Inability to taper as defined by patients on < or = 1 mg/kg/day of methylprednisolone but unable to further taper without resultant increase of acute GVHD stage.
- Patients with a reflare of a GVHD defined as worsening of 1 stage of acute GVHD in a patient who initially responded.
Who cannot join
- Relapsed malignancy.
- Acute GVHD as a result of a second or subsequent transplant or donor lymphocyte infusion (DLI).
- Active, uncontrolled infection.
- Patients who have received any second-line of immunosuppressive treatment for GVHD beyond corticosteroids and calcineurin inhibitors. Topical steroids, oral budesonide and extracorporeal photochemotherapy started at the time of steroids are allowed.
- Life-threatening infusion reaction or hypersensitivity to any formulation of ATG in the past.
- Patients who are pregnant or are breast feeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
U.T. M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Dose Finding Study of Thymoglobulin (ATG) in Patients With Steroid-Refractory Acute Graft Versus Host Disease (aGVHD)
Primary Objective:
- To determine the response and toxicity rate at day 56 of two different dose levels of thymoglobulin (ATG) [anti-thymocyte globulin (rabbit)] as a treatment of steroid-refractory acute graft versus host disease (aGVHD).
Read more
Secondary Objectives:
- To evaluate the response rate at day 28.
- To evaluate the overall survival and non-relapse mortality at 6 months.
- To determine the toxicity profile of thymoglobulin when used for the treatment of steroid-refractory aGVHD in each of two dose schedules.
- To characterize the pharmacokinetic profile of thymoglobulin in each of two dose schedules.
- To analyze biomarkers of cellular drug effect by quantifying T-cell apoptosis in aims of finding the minimal effective dose.
- To determine immune-reconstitution after administration of thymoglobulin to patients with steroid-refractory aGVHD for each dose schedule.
Read the detailed description
GvHD is a common side effect of a stem cell transplant. It is caused by a type of white blood cell (a lymphocyte). ATG is designed to kill lymphocytes and is commonly used to help prevent or treat GvHD and to treat steroid-refractory aGvHD.
Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will be asked questions about your medical history. You will have a complete physical exam. You will have blood drawn (about 2 tablespoons) for routine tests and to check for any viral infections. Women who are able to have children must have a negative blood (about 1 teaspoon) or urine pregnancy test. You will also have a biopsy of the site that is suspected to be affected by aGvHD. The study doctor will describe the type of biopsy procedure you will have, which will depend on the part of the body that is affected by the disease. If you had an earlier biopsy performed that confirmed aGvHD, you will not need a biopsy repeated for this study.
If you are found to be eligible to participate in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups. Participants in Group 1 will receive a higher dose of ATG by vein. Participants in Group 2 will receive a lower dose of ATG by vein. You will have an equal chance of being in 1 of the 2 groups. Participants in both groups will receive doses of ATG over 4-6 hours, 1 time a day every other day for a total of 3 doses.
During this study, you will be able to remain on steroids and any other drugs you may be receiving for treatment of aGvHD (such as tacrolimus or cyclosporine). You will also have blood drawn (about 1 teaspoon) to learn the effect of ATG on the lymphocytes.
You will be taken off this study, if the disease is stable as determined by the study doctor, if the disease gets worse, or you experience any intolerable side effects. If you are taken off this study, your study doctor will discuss other treatment options with you.
After you finish receiving the study medication, you will come to the clinic at regularly scheduled follow-up visits. At first, you will be seen in the clinic once a week for 1 month. You will also have additional blood drawn (about 2 teaspoons) for biomarker testing (testing that looks at how the drug is working in your body). After the first month of follow-up visits, you will come in for visits every other week while you are on this study, which will continue until you have at least 2 consecutive (back to back) evaluations of the disease status to see if the disease is stable.
This is an investigational study. ATG is FDA approved and commercially available. You and/or your insurance provider will be financially responsible for the cost of ATG while you are on this study. Up to 40 patients will take part in this study. All will be enrolled at M.D. Anderson.
- Conditions
- Graft vs Host Disease
- Being tested
- Low Dose Thymoglobulin (ATG), High Dose Thymoglobulin (ATG)
- Keywords
- Acute Graft versus Host Disease, aGVHD, Blood And Marrow Transplantation, Thymoglobulin, ATG
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose Thymoglobulin (ATG)Drug
Also called ATG, Antithymocyte Globulin
2.5 mg /kg by vein every other day for 3 doses (total dose = 7.5 mg/ kg).
High Dose Thymoglobulin (ATG)Drug
Also called ATG, Antithymocyte Globulin
1.25mg/kg by vein every other day for 3 doses (total dose = 3.75mg/kg)
| Study group | Role | What they receive |
|---|---|---|
| High Dose Thymoglobulin (ATG) | Experimental | High Dose Thymoglobulin (ATG): 1.25mg/kg by vein every other day for 3 doses (total dose = 3.75mg/kg) Receives: Drug: High Dose Thymoglobulin (ATG) |
| Low Dose Thymoglobulin (ATG) | Experimental | Low Dose Thymoglobulin (ATG): 2.5 mg /kg by vein every other day for 3 doses (total dose = 7.5 mg/ kg). Receives: Drug: Low Dose Thymoglobulin (ATG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
Response assessed at day 56, and a complete response or partial response considered a success. A toxic event defined as a life threatening infection, any death due to infection, or any death considered to be directly related to the administration of ATG.
Measured: Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2006 (estimated)
- Study startDec 2006
- Primary completionAug 2007
- Study completionAug 2007
Why it stopped: Lack of Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Amin M. Alousi, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00409695
- Sponsor's protocol ID
- 2006-0370
- Status last verified
- Jan 2012
- First submitted
- 7 Dec 2006
- Last updated
- 23 Jan 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Finding Study of Thymoglobulin (ATG) in Patients With Steroid-Refractory Acute Graft Versus Host Disease (aGVHD)
- ClinicalTrials.gov ID
- NCT00409695
- Acronym / sponsor ID
- 2006-0370
- Conditions
- Graft vs Host Disease
- Keywords
- Acute Graft versus Host Disease, aGVHD, Blood And Marrow Transplantation, Thymoglobulin, ATG
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Dec 2006
- Primary completion
- Aug 2007 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 11 Dec 2006 (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.
Primary Objective:
- To determine the response and toxicity rate at day 56 of two different dose levels of thymoglobulin (ATG) [anti-thymocyte globulin (rabbit)] as a treatment of steroid-refractory acute graft versus host disease (aGVHD).
Secondary Objectives:
- To evaluate the response rate at day 28.
- To evaluate the overall survival and non-relapse mortality at 6 months.
- To determine the toxicity profile of thymoglobulin when used for the treatment of steroid-refractory aGVHD in each of two dose schedules.
- To characterize the pharmacokinetic profile of thymoglobulin in each of two dose schedules.
- To analyze biomarkers of cellular drug effect by quantifying T-cell apoptosis in aims of finding the minimal effective dose.
- To determine immune-reconstitution after administration of thymoglobulin to patients with steroid-refractory aGVHD for each dose schedule.
Detailed description
GvHD is a common side effect of a stem cell transplant. It is caused by a type of white blood cell (a lymphocyte). ATG is designed to kill lymphocytes and is commonly used to help prevent or treat GvHD and to treat steroid-refractory aGvHD.
Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will be asked questions about your medical history. You will have a complete physical exam. You will have blood drawn (about 2 tablespoons) for routine tests and to check for any viral infections. Women who are able to have children must have a negative blood (about 1 teaspoon) or urine pregnancy test. You will also have a biopsy of the site that is suspected to be affected by aGvHD. The study doctor will describe the type of biopsy procedure you will have, which will depend on the part of the body that is affected by the disease. If you had an earlier biopsy performed that confirmed aGvHD, you will not need a biopsy repeated for this study.
If you are found to be eligible to participate in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups. Participants in Group 1 will receive a higher dose of ATG by vein. Participants in Group 2 will receive a lower dose of ATG by vein. You will have an equal chance of being in 1 of the 2 groups. Participants in both groups will receive doses of ATG over 4-6 hours, 1 time a day every other day for a total of 3 doses.
During this study, you will be able to remain on steroids and any other drugs you may be receiving for treatment of aGvHD (such as tacrolimus or cyclosporine). You will also have blood drawn (about 1 teaspoon) to learn the effect of ATG on the lymphocytes.
You will be taken off this study, if the disease is stable as determined by the study doctor, if the disease gets worse, or you experience any intolerable side effects. If you are taken off this study, your study doctor will discuss other treatment options with you.
After you finish receiving the study medication, you will come to the clinic at regularly scheduled follow-up visits. At first, you will be seen in the clinic once a week for 1 month. You will also have additional blood drawn (about 2 teaspoons) for biomarker testing (testing that looks at how the drug is working in your body). After the first month of follow-up visits, you will come in for visits every other week while you are on this study, which will continue until you have at least 2 consecutive (back to back) evaluations of the disease status to see if the disease is stable.
This is an investigational study. ATG is FDA approved and commercially available. You and/or your insurance provider will be financially responsible for the cost of ATG while you are on this study. Up to 40 patients will take part in this study. All will be enrolled at M.D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Dose Thymoglobulin (ATG) | Experimental | Drug: High Dose Thymoglobulin (ATG)High Dose Thymoglobulin (ATG): 1.25mg/kg by vein every other day for 3 doses (total dose = 3.75mg/kg) |
| Low Dose Thymoglobulin (ATG) | Experimental | Drug: Low Dose Thymoglobulin (ATG)Low Dose Thymoglobulin (ATG): 2.5 mg /kg by vein every other day for 3 doses (total dose = 7.5 mg/ kg). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients who underwent their first allogeneic transplant for any malignancy and with any cell (bone marrow, peripheral stem cell, cord blood) or donor (matched or mismatched related or unrelated) source.
- Biopsy-proven, grade II-IV aGVHD following allogeneic hematopoietic stem cell transplantation (HSCT) of any source (bone marrow, peripheral blood or cord blood stem cells). Enrollment may be started prior to results of biopsy in cases of high clinical suspicion for aGVHD.
- Early steroid-refractory aGVHD. This is defined as any NR or PD after a minimum of 3 days and not more than 1 week of 1 mg/kg/day of methylprednisolone.
- Ability to sign informed consent.
- Ability to return for clinical follow-up as specified in the protocol.
Key exclusion criteria (6 listed)
- Relapsed malignancy.
- Acute GVHD as a result of a second or subsequent transplant or donor lymphocyte infusion (DLI).
- Active, uncontrolled infection.
- Patients who have received any second-line of immunosuppressive treatment for GVHD beyond corticosteroids and calcineurin inhibitors. Topical steroids, oral budesonide and extracorporeal photochemotherapy started at the time of steroids are allowed.
- Life-threatening infusion reaction or hypersensitivity to any formulation of ATG in the past.
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 |
|---|---|---|
| Low Dose Thymoglobulin (ATG)Also: ATG, Antithymocyte Globulin2.5 mg /kg by vein every other day for 3 doses (total dose = 7.5 mg/ kg). | Drug | Low Dose Thymoglobulin (ATG) |
| High Dose Thymoglobulin (ATG)Also: ATG, Antithymocyte Globulin1.25mg/kg by vein every other day for 3 doses (total dose = 3.75mg/kg) | Drug | High Dose Thymoglobulin (ATG) |
Primary outcome
Response Rate
Time frame: Day 56
Response assessed at day 56, and a complete response or partial response considered a success. A toxic event defined as a life threatening infection, any death due to infection, or any death considered to be directly related to the administration of ATG.
Results and safety
The study was stopped early (reason given: Lack of Accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2012.
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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.
Amin M. Alousi, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Low Dose Thymoglobulin (ATG) and High Dose Thymoglobulin (ATG) in people with Graft vs Host Disease, run by M.D. Anderson Cancer Center 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 7 inclusion and 6 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 23 Jan 2012. 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 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 was stopped early (reason given: Lack of Accrual). Results are not available in the source record.
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?
Response Rate (time frame: Day 56). 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 23 Jan 2012.