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| ID | Type | Description | Link |
|---|---|---|---|
| P01CA142106 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| Prometheus Laboratories | INDUSTRY |
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Chronic GVHD is a medical condition that may occur after a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize the your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host-disease. It is thought that IL-2 may help control chronic GVHD by stopping the donor's immune system from 'rejecting' your body. In this research study, we are looking to see how IL-2 can be used in combination with steroids to treat cGVHD.
You will give yourself or be given IL-2 daily through an injection under your skin. You should rotate the injection site, if possible. You will do this once every day for 12 weeks. You will then have 4 weeks off of IL-2. During the first 6 weeks of IL-2, you will continue to take steroids without changing the dose your doctor has set for you while you are on IL-2. After 6 weeks of IL-2 therapy, your doctor may reduce the amount of steroids you take.
While you are on study, a member of the study team will examine you to evaluate your cGVHD. These assessments may include examination of your skin, joints/muscles, eyes, mouth, lungs and gastrointestinal system.
You will have clinic visits for evaluation of toxicity and clinical benefit approximately every 4 weeks. You will also have immunologic assays approximately every 8 weeks. Immunologic assays will measure the effect of IL-2 on immune cells.
You will be on the study for about 16 weeks. You may continue on study treatment for longer if you experience a clinical benefit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Interleukin-2 | Experimental | Each study participant will receive daily subcutaneous IL-2 (1 x 106 IU/m2/day) for self-administration for 12 weeks, followed by a 4-week hiatus. IL-2 will be typically administered on an outpatient basis. After completing the 16 week study (12 weeks of IL-2 study treatment and a mandatory 4 weeks off-IL-2), patients experiencing clinical benefit (complete or partial response; as well as minor response not meeting NIH criteria for partial response) with an acceptable toxicity profile will be permitted to continue extended-duration treatment indefinitely at the discretion of the treating physician. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Interleukin-2 | Drug | Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD | Participants were evaluated according to the cGVHD NIH Consensus criteria at baseline, 6 weeks, and 12 weeks on study. Per cGVHD NIH Consensus criteria, cGVHD involved organ systems are given a grade 0-3 and an overall cGVHD score, from 0-10, is given. Complete Response is defined as resolution of all reversible manifestations in each organ or site of cGVHD. A partial response is defined as an improvement in measure at least one organ or site, or decrease in global ratings by at least a 2-point change on the 10-point scale, without progression measured at any other organ or site. Non-responders have no change in cGVHD meeting criteria for either partial response or disease progression. Progressive disease is defined as an increase in organ or site scales (1-point change on a 3-point scale) or 2- to 3-point increase on the global cGVHD ratings. Clinical worsening of cGVHD is not synonymous with progressive cGVHD per NIH criteria. | Baseline, 6 weeks, and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Toxicity of 12-week Course of Low-dose SC IL-2 Therapy | Participants were evaluated at clinical visits for toxicities related to IL-2 throughout their 12-week treatment course | 12 weeks |
| Prednisone Taper With IL-2 Therapy |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Koreth, MBBS, DPhil | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02214 | United States | ||
| Massachusetts General Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | Interleukin-2 | Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Interleukin-2 | Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Overall Response Rate of Low-dose Daily SC IL-2 in Steroid-refractory cGVHD | Participants were evaluated according to the cGVHD NIH Consensus criteria at baseline, 6 weeks, and 12 weeks on study. Per cGVHD NIH Consensus criteria, cGVHD involved organ systems are given a grade 0-3 and an overall cGVHD score, from 0-10, is given. Complete Response is defined as resolution of all reversible manifestations in each organ or site of cGVHD. A partial response is defined as an improvement in measure at least one organ or site, or decrease in global ratings by at least a 2-point change on the 10-point scale, without progression measured at any other organ or site. Non-responders have no change in cGVHD meeting criteria for either partial response or disease progression. Progressive disease is defined as an increase in organ or site scales (1-point change on a 3-point scale) or 2- to 3-point increase on the global cGVHD ratings. Clinical worsening of cGVHD is not synonymous with progressive cGVHD per NIH criteria. | 33 of 35 patients were evaluable for response criteria. To be evaluable, patients had to receive at least 6 weeks of daily IL-2 and had their disease re-assessed. | Posted | Number | participants | Baseline, 6 weeks, and 12 weeks |
From first dose of study drug at Week 1 until Week 16 visit.
Participants were evaluated for adverse events at every clinical visit during Weeks 1,2,4,6,8.10,12,16 and every 4 weeks on extended duration therapy. Only serious adverse events and other adverse events that occurred during the 16-week study period are recorded here. Per protocol, only AEs Grade 3 or higher were recorded.
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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 | Interleukin-2 | Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment | These events were deemed unrelated to study treatment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Platelet count decreased | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment | This event was deemed possibly related to study treatment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Koreth, MBBS, DPhil | Dana-Farber Cancer Institute | 617-632-2949 | JKoreth@partners.org |
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| ID | Term |
|---|---|
| D000092122 | Bronchiolitis Obliterans Syndrome |
| ID | Term |
|---|---|
| D000092124 | Organizing Pneumonia |
| D001989 | Bronchiolitis Obliterans |
| D001988 | Bronchiolitis |
| D001991 | Bronchitis |
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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 had their steroid dose assessed at weeks 6, 12,16, and every 8 weeks while on extended duration IL-2 therapy.
| End of treatment after 16 weeks or most recent follow-up date for patients on extended |
| Overall Survival and Progression-free Survival | Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. OS was defined as from the study entry to death from any cause. Patients who were alive or lost to follow-up were censored at the time last seen alive. PFS was defined from the study entry to disease relapse or progression or death from any cause, whichever occurred first. | 2 years from start of IL-2 |
| Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts | Blood samples were collected throughout the patient's 12 weeks of IL-2 treatment and after the 4 week hiatus. The CD4+CD25+FOXP3+ regulatory T cells (Treg) counts were measured. | 16 weeks of study follow-up |
| Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio | Blood samples were collected throughout the patient's 12 weeks of IL-2 treatment and after the 4 week hiatus. The ratio between CD4+CD25+FOXP3+ regulatory T cells (Treg) and CD4 conventional T cell (Tcon) counts were measured. | 16 weeks of study follow-up |
| Boston |
| Massachusetts |
| 02214 |
| United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Time from Allogeneic Stem Cell Transplant | Median | Full Range | days |
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| Time from chronic GVHD onsent | Median | Full Range | days |
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| Number of cGVHD organ sites | Median | Full Range | organs affected by cGVHD |
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| Number of concurrent cGVHD therapies | Median | Full Range | therapies |
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| Baseline Corticosteroid (Prednisone) dose | Median | Full Range | milligrams per day |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Interleukin-2 | Interleukin-2: Daily subcutaneous IL-2 (1 x 10^6 IU/m^2/day) for self-administration for 12 weeks followed by 4-week hiatus |
|
|
| Secondary | Toxicity of 12-week Course of Low-dose SC IL-2 Therapy | Participants were evaluated at clinical visits for toxicities related to IL-2 throughout their 12-week treatment course | Grade 2 or higher, related to IL-2, adverse events (AE) were recorded for participants during their 12-week IL-2 treatment course. AE's were evaluated based on the CTCAE version 4.0. | Posted | Number | Grade 2 or higher related AEs | 12 weeks |
|
|
|
| Secondary | Prednisone Taper With IL-2 Therapy | Participants had their steroid dose assessed at weeks 6, 12,16, and every 8 weeks while on extended duration IL-2 therapy. | Participant's steroid taper was measured using their steroid dose at the start of therapy and their dose at the end of 16 weeks. For participants who continued on extended duration therapy, their final steroid dose was determined at the time of stopping treatment or, if still ongoing, the last clinic visit at the time of data analysis. | Posted | Mean | Full Range | percent taper | End of treatment after 16 weeks or most recent follow-up date for patients on extended |
|
|
|
| Secondary | Overall Survival and Progression-free Survival | Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. OS was defined as from the study entry to death from any cause. Patients who were alive or lost to follow-up were censored at the time last seen alive. PFS was defined from the study entry to disease relapse or progression or death from any cause, whichever occurred first. | Posted | Number | probability | 2 years from start of IL-2 |
|
|
|
| Secondary | Immunologic Effects of Low-dose Daily SC IL-2: Treg Cell Counts | Blood samples were collected throughout the patient's 12 weeks of IL-2 treatment and after the 4 week hiatus. The CD4+CD25+FOXP3+ regulatory T cells (Treg) counts were measured. | Posted | Median | Inter-Quartile Range | cell count/ uL | 16 weeks of study follow-up |
|
|
|
| Secondary | Immunologic Effects of Low-dose Daily SC IL-2: Treg/Tcon Ratio | Blood samples were collected throughout the patient's 12 weeks of IL-2 treatment and after the 4 week hiatus. The ratio between CD4+CD25+FOXP3+ regulatory T cells (Treg) and CD4 conventional T cell (Tcon) counts were measured. | Posted | Median | Inter-Quartile Range | ratio | 16 weeks of study follow-up |
|
|
|
| 4 |
| 35 |
| 10 |
| 35 |
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| Pneumothorax | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | These events were deemed unrelated to study treatment |
|
| Streptococcus viridans infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment | This event was deemed unrelated to study treatment. |
|
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| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment | This event was deemed probably related to study treatment |
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| Flu-like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment | This event was deemed related to study treatment |
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| Hypertension | Cardiac disorders | CTCAE (4.0) | Systematic Assessment | This event was deemed unrelated to study therapy |
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| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment | This event was deemed unrelated to study therapy |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment | This event was deemed unrelated to study therapy |
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| Peripheral Motor Neuropathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment | This event was deemed unrelated to study therapy |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment | This event was deemed unrelated to study therapy |
|
| Thromoembolic Event | Vascular disorders | CTCAE (4.0) | Systematic Assessment | This event was deemed unrelated to study therapy |
|
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| D001982 |
| Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D006086 | Graft vs Host Disease |
| D007154 | Immune System Diseases |
| D000602 |
| Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |
| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
|