Graft-vs-Host DiseasePhase 1NCT01940796
Phase I Trial of Brentuximab Vedotin for Refractory Chronic Graft-vs.-Host Disease (GVHD)
A Phase 1 study testing Brentuximab Vedotin in people with Graft-vs-Host Disease and GVHD, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This research study is trying to determine the safest dose of Brentuximab Vedotin that can be given to patients with chronic GVHD and see if chronic GVHD improves. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft-vs-Host Disease, GVHD
- What is being tested?
- Brentuximab Vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Dec 2016
- Phase
- Phase 1
- 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
- Recipients of allogeneic hematopoietic cell transplantation (HCT) after either myeloablative or reduced intensity conditioning regimens. Any donor source of stem cells is eligible.
- Participants must be at least 100 days after HCT.
- Patients must have steroid refractory cGVHD, defined as having persistent signs and symptoms of chronic GVHD (section 13.1) despite the use of prednisone at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks in the preceding 12 months (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms.
- Stable dose of corticosteroids for 4 weeks prior to enrollment
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin inhibitors, sirolimus, mycophenolate mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
- Serum Cr ≤ 3 gm / dL
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- Adequate hepatic function (total bilirubin < 2.0 mg/dl, AST < 5x ULN), unless hepatic dysfunction is a manifestation of presumed cGVHD. For patients with abnormal LFTs as the sole manifestation of active cGVHD, documented cGVHD on liver biopsy will be required prior to enrollment. Abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with active hepatic cGVHD, and a liver biopsy will not be mandated in this situation.
- Patients must have adequate bone marrow function as defined by ANC ≥ 1000 / µl and platelets ≥ 20,000 / µl without growth factor or transfusional support
- Negative pregnancy test for females of child bearing age
- Age ≥ 18 - The safety and effectiveness of brentuximab vedotin has not been established in the pediatric population. Clinical trials of brentuximab vedotin included only 9 pediatric patients and this number is not sufficient to determine whether they respond differently than adult patients.
- The effects of brentuximab vedotin on the developing human fetus are unknown. For this reason and because chemotherapy agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
- Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment.
- ECP therapy within 4 weeks prior to enrollment
- Active malignant disease relapse
- Active, uncontrolled infection
- Uncontrolled cardiac angina or symptomatic congestive heart failure (NYHA Class III or IV).
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- Karnofsky performance status < 30
- Prior use of brentuximab vedotin for GVHD is not allowed. Prior use of brentuximab vedotn for the treatment of malignancy is allowed.
- Pregnant women are excluded from this study because brentuximab vedotin is a chemotherapy agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with brentuximab vedotin, breastfeeding should be discontinued if the mother is treated with brentuximab vedotin.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02215
About this study
This research study is trying to determine the safest dose of Brentuximab Vedotin that can be given to patients with chronic GVHD and see if chronic GVHD improves.
Read the detailed description
This study is looking for the highest dose of the Brentuximab Vedotin that can be administered safely without severe or unmanageable side effects in patients that have chronic Graft vs. Host Disease, not everyone who participates in this research study will receive the same dose of the study drug. The dose each patient will get depends on the number of participants who have been enrolled in the study prior and how well they have tolerated their doses.
Each patient will receive a dose of Brentuximab Vedotin every 3 weeks. Brentuximab Vedotin is administered via intravenous infusion, or IV infusion, which means directly into the vein, over a period of about 30 minutes.
Each cycle is 21 days long.
Each patient will undergo the following tests and procedures when they come into the clinic to receive each dose of Brentuximab Vedotin:
Days 1, 8, and 15 of 1st 2 cycles:
- Physical exam, which includes height, weight, body surface area and vital signs.
- A medical history, which includes questions about your health, current medications, and any allergies.
- Performance status, which evaluates how participant are able to carry on with your usual activities.
- Routine blood tests to test overall health (about 1 teaspoon of blood) Assessment of side effects- physician will evaluate the patient's current health and ask questions to see there are any experienced side effects from taking the study drug.
Only Day 1 of 1st 3 cycles:
- Research blood draws for biomarker and PK assessments (pharmacokinetic assessments that measure the level of drug in the patient's blood) (about 4 teaspoons of blood)
- Biomarker studies blood draw (about 4 teaspoons) Viral monitoring blood tests to make sure each patient has not developed any new viruses as a result of treatment (about 4 teaspoons of blood)
- Chronic GVHD assessments: The patient's physician may need to perform other tests to confirm the diagnosis of acute GVHD. These can include more blood tests, imaging studies, and possibly biopsies of affected organs. The exact tests will be determined by the patient's physician
Planned Follow-up: If the patient's physician believes the patient is responding well to treatment, the patient may receive up to 16 cycles of Brentuximab Vedotin. The Investigator would like to keep track of patient's medical condition for 12 months after the patient has completed the first 2 cycles of treatment, no matter if the patient receives more doses or not. The Investigator would like to do this by calling the patient on the telephone to see how he/she is doing. Keeping in touch with patient and checking the condition helps the Investigator look at the long-term effects of the research study.
- Conditions
- Graft-vs-Host Disease, GVHD
- Being tested
- Brentuximab Vedotin
- Keywords
- Brentuximab Vedotin, GVHD, Refractory Chronic Graft vs Host Disease
- 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.
Brentuximab VedotinDrug
Up to five dose levels will be tested in cohorts of 3-6 participants each. Once the maximum tolerated dose (MTD) is established, 10 more participants will be treated at the MTD for analysis of efficacy.
| Study group | Role | What they receive |
|---|---|---|
| Brentuximab Vedotin | Experimental | The dose of brentuximab Vedotin will be based on the cohort the participant is enrolled on. Dosing will be based on the participant's weight prior to each dose. Actual weight will be used except for participants weighing > 100 kg. The dose for participants weighing > 100 Kg will be calculated based on a weight of 100 kg. The dose should be rounded to the nearest whole number of milligrams. Brentuximab vedotin will be administered over approximately 30 minutes IV.Up to five dose levels will be tested in cohorts of 3-6 participants each. Once the maximum tolerated dose (MTD) is established, 10 more participants will be treated at the MTD for analysis of efficacy. Receives: Drug: Brentuximab Vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To define the maximum tolerated dose (MTD) of brentuximab vedotin when given as treatment for refractory chronic GVHD
To define the maximum tolerated dose (MTD) of brentuximab vedotin when given as treatment for refractory chronic GVHD
Measured: 2 Years
Secondary outcomes (5)
To test the overall response rate of Brentuximab Vedotin when given as treatment for refractory chronic GVHD
To test the overall response rate of Brentuximab Vedotin when given as treatment for refractory chronic GVHD
Measured: 2 Years
To identify the toxicities associated with Brentuximab Vedotin when used as therapy for refractory chronic GVHD
To identify the toxicities associated with Brentuximab Vedotin when used as therapy for refractory chronic GVHD
Measured: 2 Years
Overall Survival
Overall survival at 100 days, 180 days, and one year after first infusion
Measured: 2 Years
To assess levels of soluble CD30 and surface CD30 expression on peripheral blood T-cells in participants with chronic GVHD before and after the administration of brentuximab vedotin
To assess levels of soluble CD30 and surface CD30 expression on peripheral blood T-cells in participants with chronic GVHD before and after the administration of brentuximab vedotin
Measured: 2 Years
To assess dose of steroids (mg/kg/day of prednisone equivalent) at 6 and 12 months after starting therapy
To assess dose of steroids (mg/kg/day of prednisone equivalent) at 6 and 12 months after starting therapy
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2013 (estimated)
- Study startOct 2013
- Primary completionDec 2016
- Study completionDec 2016
Why it stopped: Toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft-vs-Host DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Seagen Inc.
- Responsible party
- Principal investigator, Yi-Bin A. Chen, MD, Massachusetts General Hospital
- Investigators
- Yi-Bin Chen, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01940796
- Sponsor's protocol ID
- 13-239
- Status last verified
- Jul 2018
- First submitted
- 9 Sep 2013
- Last updated
- 26 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Chen YB, Perales MA, Li S, Kempner M, Reynolds C, Brown J, Efebera YA, Devine SM, El-Jawahri A, McAfee SL, Spitzer TR, Soiffer RJ, Ritz J, Cutler C. Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease. Blood. 2017 Jun 15;129(24):3256-3261. doi: 10.1182/blood-2017-03-772210. Epub 2017 May 4.
PubMed 28473406
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Brentuximab Vedotin for Refractory Chronic Graft-vs.-Host Disease (GVHD)
- ClinicalTrials.gov ID
- NCT01940796
- Acronym / sponsor ID
- 13-239
- Conditions
- Graft-vs-Host Disease, GVHD
- Keywords
- Brentuximab Vedotin, GVHD, Refractory Chronic Graft vs Host Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Toxicity
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Seagen Inc.
- Study start
- Oct 2013 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 12 Sep 2013 (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 research study is trying to determine the safest dose of Brentuximab Vedotin that can be given to patients with chronic GVHD and see if chronic GVHD improves.
Detailed description
This study is looking for the highest dose of the Brentuximab Vedotin that can be administered safely without severe or unmanageable side effects in patients that have chronic Graft vs. Host Disease, not everyone who participates in this research study will receive the same dose of the study drug. The dose each patient will get depends on the number of participants who have been enrolled in the study prior and how well they have tolerated their doses.
Each patient will receive a dose of Brentuximab Vedotin every 3 weeks. Brentuximab Vedotin is administered via intravenous infusion, or IV infusion, which means directly into the vein, over a period of about 30 minutes.
Each cycle is 21 days long.
Each patient will undergo the following tests and procedures when they come into the clinic to receive each dose of Brentuximab Vedotin:
Days 1, 8, and 15 of 1st 2 cycles:
- Physical exam, which includes height, weight, body surface area and vital signs.
- A medical history, which includes questions about your health, current medications, and any allergies.
- Performance status, which evaluates how participant are able to carry on with your usual activities.
- Routine blood tests to test overall health (about 1 teaspoon of blood) Assessment of side effects- physician will evaluate the patient's current health and ask questions to see there are any experienced side effects from taking the study drug.
Only Day 1 of 1st 3 cycles:
- Research blood draws for biomarker and PK assessments (pharmacokinetic assessments that measure the level of drug in the patient's blood) (about 4 teaspoons of blood)
- Biomarker studies blood draw (about 4 teaspoons) Viral monitoring blood tests to make sure each patient has not developed any new viruses as a result of treatment (about 4 teaspoons of blood)
- Chronic GVHD assessments: The patient's physician may need to perform other tests to confirm the diagnosis of acute GVHD. These can include more blood tests, imaging studies, and possibly biopsies of affected organs. The exact tests will be determined by the patient's physician
Planned Follow-up: If the patient's physician believes the patient is responding well to treatment, the patient may receive up to 16 cycles of Brentuximab Vedotin. The Investigator would like to keep track of patient's medical condition for 12 months after the patient has completed the first 2 cycles of treatment, no matter if the patient receives more doses or not. The Investigator would like to do this by calling the patient on the telephone to see how he/she is doing. Keeping in touch with patient and checking the condition helps the Investigator look at the long-term effects of the research study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Brentuximab Vedotin | Experimental | Drug: Brentuximab VedotinThe dose of brentuximab Vedotin will be based on the cohort the participant is enrolled on. Dosing will be based on the participant's weight prior to each dose. Actual weight will be used except for participants weighing > 100 kg. The dose for participants weighing > 100 Kg will be calculated based on a weight of 100 kg. The dose should be rounded to the nearest whole number of milligrams. Brentuximab vedotin will be administered over approximately 30 minutes IV.Up to five dose levels will be tested in cohorts of 3-6 participants each. Once the maximum tolerated dose (MTD) is established, 10 more participants will be treated at the MTD for analysis of efficacy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Recipients of allogeneic hematopoietic cell transplantation (HCT) after either myeloablative or reduced intensity conditioning regimens. Any donor source of stem cells is eligible.
- Participants must be at least 100 days after HCT.
- Patients must have steroid refractory cGVHD, defined as having persistent signs and symptoms of chronic GVHD (section 13.1) despite the use of prednisone at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks in the preceding 12 months (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms.
- Stable dose of corticosteroids for 4 weeks prior to enrollment
- No addition or subtraction of other immunosuppressive medications (e.g., calcineurin inhibitors, sirolimus, mycophenolate mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
Key exclusion criteria (9 listed)
- Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
- Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment.
- ECP therapy within 4 weeks prior to enrollment
- Active malignant disease relapse
- Active, uncontrolled infection
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 |
|---|---|---|
| Brentuximab VedotinUp to five dose levels will be tested in cohorts of 3-6 participants each. Once the maximum tolerated dose (MTD) is established, 10 more participants will be treated at the MTD for analysis of efficacy. | Drug | Brentuximab Vedotin |
Primary outcome
To define the maximum tolerated dose (MTD) of brentuximab vedotin when given as treatment for refractory chronic GVHD
Time frame: 2 Years
To define the maximum tolerated dose (MTD) of brentuximab vedotin when given as treatment for refractory chronic GVHD
5 secondary outcomes
To test the overall response rate of Brentuximab Vedotin when given as treatment for refractory chronic GVHD
Time frame: 2 Years
To identify the toxicities associated with Brentuximab Vedotin when used as therapy for refractory chronic GVHD
Time frame: 2 Years
Overall Survival
Time frame: 2 Years
To assess levels of soluble CD30 and surface CD30 expression on peripheral blood T-cells in participants with chronic GVHD before and after the administration of brentuximab vedotin
Time frame: 2 Years
To assess dose of steroids (mg/kg/day of prednisone equivalent) at 6 and 12 months after starting therapy
Time frame: 2 Years
Results and safety
The study was stopped early (reason given: Toxicity). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2018.
- Derived from this study: PubMed 28473406Chen YB, Perales MA, Li S, Kempner M, Reynolds C, Brown J, Efebera YA, Devine SM, El-Jawahri A, McAfee SL, Spitzer TR, Soiffer RJ, Ritz J, Cutler C. Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease. Blood. 2017 Jun 15;129(24):3256-3261. doi: 10.1182/blood-2017-03-772210. Epub 2017 May 4.
- Individual participant dataSharing planned: No
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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.
Yi-Bin Chen, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Brentuximab Vedotin in people with Graft-vs-Host Disease and GVHD, run by Massachusetts General Hospital 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 9 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 26 Jul 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 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.
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: Toxicity). 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?
To define the maximum tolerated dose (MTD) of brentuximab vedotin when given as treatment for refractory chronic GVHD (time frame: 2 Years). 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 NCT01940796, which also lists 1 linked publication.
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 26 Jul 2018.