Graft Versus Host DiseasePhase 1NCT00529035
Ultra-Low Dose Interleukin-2 for Refractory Chronic Graft Versus Host Disease
A Phase 1 study testing Interleukin-2 in people with Graft Versus Host Disease, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
The purpose of this research study is to determine the safety of IL-2 and the highest dose of this drug that can be given safely to people with chronic graft versus host disease (GVHD). Chronic GVHD is a medical condition that may occur after patients receive a bone marrow, stem cell or cord blood transplant. 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?
- Interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to 27 May 2020
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
- Patients must be at least 180 days from the allogeneic stem cell transplantation procedure
- Steroid refractory cGVHD, defined as having persistent symptoms and signs of GVHD despite the use of prednisone for at least 4 weeks in the preceding 12 months 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 for 4 weeks prior to enrollment.
- Adequate bone marrow, renal and hepatic function as outlined in the protocol
- 18 years of age or older
- ECOG Performance Status of 0-2
Who cannot join
- Ongoing prednisone requirement > 1mg/kg/day (or equivalent)
- Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment
- Concurrent ECP therapy within 4 weeks prior to enrollment
- Post-transplant exposure to any novel immunosuppressive medication within 100 days prior to enrollment
- Donor lymphocyte infusion within 100 days prior to IL-2 therapy
- Active malignant disease relapse
Show all 14Show fewer
- Active, uncontrolled infection
- Positive serologic test for Hepatitis B or a positive serologic or nucleic acid test for Hepatitis C
- HIV seropositivity
- Life expectancy < 3 months
- Pregnancy or lactation
- Inability to comply with IL-2 treatment regimen
- Uncontrolled cardiac angina or symptomatic congestive heart failure
- Organ transplant (allograft) recipient
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase I Study of Ultra-Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease
The purpose of this research study is to determine the safety of IL-2 and the highest dose of this drug that can be given safely to people with chronic graft versus host disease (GVHD). Chronic GVHD is a medical condition that may occur after patients receive a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize their body (the host) as foreign and attempt to "reject" it. Traditional standard therapy to treat chronic GVHD is prednisone (steroids). Treatment options are limited, and it is thought that IL-2 may help to control chronic GVHD.
Read the detailed description
- IL-2 will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels.
- Participants will be seen periodically while they are receiving IL-2. Physical exams and blood tests will be performed weekly for the first two weeks and then every other week until week 8.
- Conditions
- Graft Versus Host Disease
- Being tested
- Interleukin-2
- Keywords
- Chronic GVHD, Steroid refractory GVHD, allogeneic stem cell transplantation
- Medical subject headings
- Graft vs Host Disease, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interleukin-2Drug
Also called IL-2
Dose will vary depending upon when participant enters the trial: Given as a daily injection under the skin for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Interleukin-2 | Experimental | Interleukin-2 (IL-2) will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels:
Dose Level -A 0.3 x 106 (IU/m2/d) Dose Level -B 1 x 106 (IU/m2/d) Dose Level-C 3 x 106 (IU/m2/d) Receives: Drug: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids.
Three dose levels were evaluated to determine the maximally tolerated dose (MTD):
Dose level A: 0.3 x 10^6 IU/m^2/day Dose level B: 1.0 x 10^6 IU/m^2/day Dose level C: 3.0 x 10^6 IU/m^2/day Once the MTD (dose level B) was established, an additional 10 participants were enrolled at this dose.
Measured: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy
Secondary outcomes (3)
The Number of Participants Who Tolerated at Least 6 Weeks of Subcutaneous Low Dose IL-2.
Feasibility: the number of participants who tolerated at least 6 weeks of therapy, and were thus evaluable for response. Efficacy: chronic GVHD response per NIH consensus criteria in evaluable patients.
A complete response was defined as resolution of all reversible chronic GVHD-associated manifestations, a partial response as an improvement of 50% or more on the organ-specific chronic GVHD scale without progression at other organs or sites, progressive disease as an increase of 25% or more on the organ specific chronic GVHD scale, and stable disease as an improvement of less than 50% or increase of less than 25%. Please refer to the Supplementary Appendix in our published report (Koreth et al, NEJM 2011) for further details.
Measured: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy. cGVHD was assessed at Weeks 8 and 12
CD3+T, CD4+T (Including Regulatory CD4+T Cells (Treg) and Conventional CD4+T Cells (Tcon)), CD8+T, NK, NKT and B Cell Counts.
Changes in the above immune cell populations (CD3+T, CD4+T (including CD4+Treg and CD4+Tcon), CD8+T, NK, NKT and B cell counts were measured at study appointments during the 8-week IL-2 treatment and four weeks post study therapy.
All study participants (n=28) with a sample available were reported in the data table.
Immune outcome data cannot be meaningfully rendered in the template provided, owing to complexity. The tables below only represent a general overview of the data. Please refer to figure 2 in our published report (Koreth et al, NEJM 2011).
Measured: Immunological samples taken at study appointments during the 12 week protocol schedule
Treg Cell:Tcon Cell Ratio
Changes in the ratio of the CD4+ regulatory T cell (Treg) and CD4+ conventional T cell (Tcon) counts were measured at study appointments during the 8-week IL-2 treatment and four weeks post study therapy.
All study participants (n=28) with a sample available were reported in the data table.
Immune outcome data cannot be meaningfully rendered in the template provided, owing to complexity. The tables below only represent a general overview of the data. Please refer to figure 2 in our published report (Koreth et al, NEJM 2011).
Measured: Immunological samples taken at study appointments during the 12 week protocol schedule
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2007 (estimated)
- Study startAug 2007
- Primary completionJun 2011
- Study completion27 May 2020
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Novartis
- Responsible party
- Principal investigator, John Koreth, MD, Dana-Farber Cancer Institute
- Investigators
- John Koreth, MBBS, D.Phil, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00529035
- Sponsor's protocol ID
- 07-083
- Status last verified
- Jun 2020
- First submitted
- 11 Sep 2007
- Last updated
- 1 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, Armand P, Cutler C, Ho VT, Treister NS, Bienfang DC, Prasad S, Tzachanis D, Joyce RM, Avigan DE, Antin JH, Ritz J, Soiffer RJ. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011 Dec 1;365(22):2055-66. doi: 10.1056/NEJMoa1108188.
PubMed 22129252
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Ultra-Low Dose Subcutaneous Interleukin-2 (IL-2) for Treatment of Refractory Chronic Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT00529035
- Acronym / sponsor ID
- 07-083
- Conditions
- Graft Versus Host Disease
- Keywords
- Chronic GVHD, Steroid refractory GVHD, allogeneic stem cell transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Novartis
- Study start
- Aug 2007
- Primary completion
- Jun 2011 (actual)
- Study completion
- 27 May 2020 (actual)
- First posted
- 14 Sep 2007 (estimated)
- Results
- Posted 29 Jan 2014
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 research study is to determine the safety of IL-2 and the highest dose of this drug that can be given safely to people with chronic graft versus host disease (GVHD). Chronic GVHD is a medical condition that may occur after patients receive a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize their body (the host) as foreign and attempt to "reject" it. Traditional standard therapy to treat chronic GVHD is prednisone (steroids). Treatment options are limited, and it is thought that IL-2 may help to control chronic GVHD.
Detailed description
- IL-2 will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels.
- Participants will be seen periodically while they are receiving IL-2. Physical exams and blood tests will be performed weekly for the first two weeks and then every other week until week 8.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Interleukin-2 | Experimental | Drug: Interleukin-2Interleukin-2 (IL-2) will be given daily through an injection under the skin for a period of 8 weeks. To determine the highest safest dose of IL-2, the dose participants receive will increase as lower doses are determined to be safe. There will be three dose levels: Dose Level -A 0.3 x 106 (IU/m2/d) Dose Level -B 1 x 106 (IU/m2/d) Dose Level-C 3 x 106 (IU/m2/d) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
- Patients must be at least 180 days from the allogeneic stem cell transplantation procedure
- Steroid refractory cGVHD, defined as having persistent symptoms and signs of GVHD despite the use of prednisone for at least 4 weeks in the preceding 12 months 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 for 4 weeks prior to enrollment.
Key exclusion criteria (14 listed)
- Ongoing prednisone requirement > 1mg/kg/day (or equivalent)
- Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment
- Concurrent ECP therapy within 4 weeks prior to enrollment
- Post-transplant exposure to any novel immunosuppressive medication within 100 days prior to enrollment
- Donor lymphocyte infusion within 100 days prior to IL-2 therapy
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 |
|---|---|---|
| Interleukin-2Also: IL-2Dose will vary depending upon when participant enters the trial: Given as a daily injection under the skin for 8 weeks. | Drug | Interleukin-2 |
Primary outcome
The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids.
Time frame: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy
Three dose levels were evaluated to determine the maximally tolerated dose (MTD): Dose level A: 0.3 x 10^6 IU/m^2/day Dose level B: 1.0 x 10^6 IU/m^2/day Dose level C: 3.0 x 10^6 IU/m^2/day Once the MTD (dose level B) was established, an additional 10 participants were enrolled at this dose.
3 secondary outcomes
The Number of Participants Who Tolerated at Least 6 Weeks of Subcutaneous Low Dose IL-2.
Time frame: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy. cGVHD was assessed at Weeks 8 and 12
CD3+T, CD4+T (Including Regulatory CD4+T Cells (Treg) and Conventional CD4+T Cells (Tcon)), CD8+T, NK, NKT and B Cell Counts.
Time frame: Immunological samples taken at study appointments during the 12 week protocol schedule
Treg Cell:Tcon Cell Ratio
Time frame: Immunological samples taken at study appointments during the 12 week protocol schedule
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22129252Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, Armand P, Cutler C, Ho VT, Treister NS, Bienfang DC, Prasad S, Tzachanis D, Joyce RM, Avigan DE, Antin JH, Ritz J, Soiffer RJ. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011 Dec 1;365(22):2055-66. doi: 10.1056/NEJMoa1108188.
Related trials for Graft Versus Host Disease
RecruitingPhase 2
A Study of Photobiomodulation (PBM) Therapy in People With Oral Graft-Versus-Host Disease (GVHD) After Stem Cell Transplant
Graft-Versus-Host Disease, GVHD
RecruitingObservational study
Long-term Evaluation and Follow-up Care of Patients Treated With Stem Cell Transplants
Graft-versus-leukemia, Graft vs Host Disease
Not yet recruiting
Evaluating and Promoting Resilience in Adolescents With Tourette Syndrome
Tourette Syndrome, Tic Disorders
RecruitingPhase 3
A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
Chronic Graft-versus-host-disease
Active, not recruiting
Patient Reported Outcomes With UVA-1 Therapy for Treatment of Sclerosing Skin Diseases
Scleroderma, Systemic, Morphea
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.
John Koreth, MBBS, D.Phil principal investigator
Dana-Farber Cancer Institute
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 Interleukin-2 in people with Graft Versus Host Disease, run by Dana-Farber Cancer Institute 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 8 inclusion and 14 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 1 Jul 2020. 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?
Yes. Results are posted in the registry (first posted 29 Jan 2014). 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?
The Maximum Tolerated Dose and Toxicity Profile of an 8 Week Course of IL-2 in Patients With cGVHD and an Inadequate Response to Steroids. (time frame: Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy). 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 NCT00529035, 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 1 Jul 2020.