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| Name | Class |
|---|---|
| Brigham and Women's Hospital | OTHER |
| Novartis | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Interleukin-2 | Drug | Dose will vary depending upon when participant enters the trial: Given as a daily injection under the skin for 8 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Koreth, MBBS, D.Phil | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22129252 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Ultra-low Dose Interleukin-2 | Daily subcutaneous administration of Interleukin-2 evaluated at three dose levels: 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1 | 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) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | One participant terminated therapy early and was not evaluable for this outcome measure. | Posted | Number | million IU/m2/day | Participants were assessed for toxicities at mandatory study follow-up visits during the 8 week course of study therapy and four weeks post therapy |
|
12 weeks. For patients who continued on extended-duration therapy, adverse events were reported as long as they received treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ultra-low Dose Interleukin-2 | 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) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombotic microangiopathy with renal failure | Blood and lymphatic system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constitutional symptoms | General disorders | Systematic Assessment | 2 subjects had low-grade constitutional symptoms (fever, malaise, arthralgia) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Koreth, MBBS, D.Phil | Dana-Farber Cancer Institute | (617) 632-2949 | jkoreth@partners.org |
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| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| D000092122 | Bronchiolitis Obliterans Syndrome |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D000092124 | Organizing Pneumonia |
| D001989 | Bronchiolitis Obliterans |
| D001988 | Bronchiolitis |
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| ID | Term |
|---|---|
| D007376 | Interleukin-2 |
| ID | Term |
|---|---|
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
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| 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). | 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). | Immunological samples taken at study appointments during the 12 week protocol schedule |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|
| Participants |
|
|
| Secondary | 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. | Participants were evaluable for response and considered meeting the feasibility endpoint if they completed at least 6 weeks of treatment. Participants who had a partial response or complete response in cGVHD to treatment were considered to meet the efficacy endpoint. | Posted | Number | participants | 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 |
|
|
|
| Secondary | 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). | Participants were evaluated for regulatory T cell (Treg) expansion and other immune-cell changes while on low-dose IL-2 therapy. Participants had blood samples drawn at study appointments during the 12 week protocol schedule. Please note that for NK and NKT cell counts, only 18 participants samples were analyzed. | Posted | Median | Inter-Quartile Range | cells/cubic millimeter | Immunological samples taken at study appointments during the 12 week protocol schedule |
|
|
|
| Secondary | 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). | Participants were evaluated for changes to the ratio of regulatory T cell (Treg) and conventional T cell (Tcon) counts while on IL-2 therapy. Participants had blood samples drawn at study appointments during the 12 week protocol schedule to analyze the immunological effects of low-dose IL-2 therapy. | Posted | Median | Inter-Quartile Range | ratio | Immunological samples taken at study appointments during the 12 week protocol schedule |
|
|
|
| 9 |
| 29 |
| 4 |
| 29 |
| MRSA Pneumonia | Infections and infestations | Systematic Assessment | Subject with MRSA pneumonia documented prior to start of study treatment had recrudescent MRSA pneumonia at week 7. |
|
| MRSA furuncle | Infections and infestations | Systematic Assessment | MRSA furuncle preceded start of study treatment. |
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| Hemophilius influenza type B bacteremia | Infections and infestations | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | Systematic Assessment | On subject experienced a fatal acute myocardial infarction 70 days after coming off-treatment (unrelated to study treatment). Another subject, with known coronary artery disease, had a myocardial infarction at 2 weeks off-treatment. |
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| Injection site induration | General disorders | Systematic Assessment | 2 subjects experienced reversible injection site induration reactions. |
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| Renal dysfunction (mild) | Renal and urinary disorders | Systematic Assessment |
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| Thrombocytopenia (mild) | Blood and lymphatic system disorders | Systematic Assessment |
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| D001991 |
| Bronchitis |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D000602 |
| Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |
|
| CD8+ T cell count |
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| Natural Killer (NK) cell count |
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| NKT cell count |
|