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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2014-00755 | Other Identifier | NCI CTRP |
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IL-2 add-back post allogeneic hematopoietic stem cell transplant (HSCT), combined with Sirolimus (SIR), Tacrolimus (TAC) will optimize Treg reconstitution and prevent graft versus host disease (GVHD).
1) Determine if a GVHD prophylaxis regimen of IL-2/SIR/TAC enhances in vivo Treg differentiation and growth; 2) Study the safety and effects of IL-2/SIR/TAC on the incidence of acute and chronic GVHD; 3) Evaluate the influence of dual IL-2 supplementation and mammalian target of rapamycin (mTOR) inhibition on T cell-specific signaling pathways and the polarization of emerging T helper cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GVHD Regimen | Experimental | Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IL-2 | Drug | A subcutaneous injection will be administered 3 times a week (separated by at least 1 day between injections), from day 0 to +90 (+/- 7 days). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT | Percentage of Treg among blood CD4+ T cells at day 30 after hematopoietic cell transplantation (HCT), to compare to SIR/TAC alone data from a previous trial (median of 16%). The study was designed to capture an increase in regulatory T cells from a median of 16.0% at day +30. | 30 days post HCT |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival at Day +365 | Overall survival will be defined as the time from transplant date to death from any cause. | 365 days post HCT |
| Cumulative Incidence of Relapse | Incidence of primary disease relapse per standard definitions. |
| Measure | Description | Time Frame |
|---|---|---|
| Function of Blood Treg After Allogeneic HSCT | Percent of Treg suppression at day +30. Investigators had also planned to test Treg function at day +90, if sufficient Tregs had been available for analysis. | 30 days post HCT |
| Rate of Natural Killer Cell (NK) Reconstitution |
Inclusion Criteria:
Patients must have an available 8/8 human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 matched-related or unrelated donor allogeneic hematopoietic peripheral blood stem cell graft.
Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid leukemia, or myeloproliferative neoplasms requiring a matched allogeneic HSCT.
Adequate vital organ function:
Performance status: Karnofsky Performance Status Score ≥ 80%
Donor eligibility: Eligible donors will include healthy sibling, relative or unrelated donors that are matched with the patient at HLA-A, B, C, and DRB1 by high resolution typing.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brian Betts, MD | Moffitt Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28104702 | Derived | Betts BC, Pidala J, Kim J, Mishra A, Nishihori T, Perez L, Ochoa-Bayona JL, Khimani F, Walton K, Bookout R, Nieder M, Khaira DK, Davila M, Alsina M, Field T, Ayala E, Locke FL, Riches M, Kharfan-Dabaja M, Fernandez H, Anasetti C. IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation. Haematologica. 2017 May;102(5):948-957. doi: 10.3324/haematol.2016.153072. Epub 2017 Jan 19. |
| Label | URL |
|---|---|
| H. Lee Moffitt Cancer Center \& Research Institute | View source |
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Participants were enrolled at Moffitt Cancer Center, April 2014 through December 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | GVHD Regimen | Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
All participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | GVHD Regimen | Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT). |
| 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 | Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT | Percentage of Treg among blood CD4+ T cells at day 30 after hematopoietic cell transplantation (HCT), to compare to SIR/TAC alone data from a previous trial (median of 16%). The study was designed to capture an increase in regulatory T cells from a median of 16.0% at day +30. | All participants. | Posted | Median | Full Range | percentage of CD4+Tregs | 30 days post HCT |
|
|
2 years, 6 months
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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 | GVHD Regimen | Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ileus | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
Strategies to overcome interference from soluble IL-2 receptor and STAT3-mediated acute GVHD are needed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Brian Betts | H. Lee Moffitt Cancer Center and Research Institute | 813-745-5410 | brian.betts@moffitt.org |
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| ID | Term |
|---|---|
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D007376 | Interleukin-2 |
| C082598 | aldesleukin |
| D016559 | Tacrolimus |
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
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|
| Tacrolimus | Drug | Will be administered at 0.01 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3 |
|
| Sirolimus | Drug | Orally on day -1. The dose for loading is 12 mg by mouth (PO) |
|
|
| 1 year post HCT |
| Cumulative Incidence of Grade II-IV Acute GVHD by Day +100 | Acute GVHD will be graded per the 1995 consensus guidelines. | 100 days post HCT |
| Cumulative Incidence of Chronic GVHD by Day +365 | Cumulative incidence of chronic GVHD by day +365 per NIH Consensus criteria. | 365 days post HCT |
| Incidence of Non-relapse Death | Incidence of Non-relapse death/Transplant-related mortality. Non-relapse death is defined as death in continuous remission from primary disease requiring transplantation. | 365 days post HCT |
| Incidence of Unexpected or Serious Adverse Events (AEs) | Grade 3-5 unexpected or serious adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.03) were captured up to day +130 or 30 days after the last dose of IL-2. Events listed, with causality in relation to study treatment noted. | Up to days 130 post HCT |
| Proportion of Treg Among Blood CD4+ T Cells at Day +90 After HCT | The proportion of Tregs to non-Treg CD4+ cells to be assessed at day +90. Natural Killer Cells (NKs): Median K/uL NK cells. | 90 days post HCT |
| STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 30 | Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +30. | 30 days post HCT |
| STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 90 | Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +90. | 90 days post HCT |
Investigators planned to monitor natural killer cell (NK) reconstitution. Standard immune deficiency flow cytometry panels (IDP) was to be drawn on days +90, +180, and +365 to evaluate NK reconstitution. Results of standard lab tests to be compared to compiled data at a later date |
| 365 days post HCT |
| IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation | View source |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Participants |
|
|
| Secondary | Overall Survival at Day +365 | Overall survival will be defined as the time from transplant date to death from any cause. | All participants. | Posted | Number | 95% Confidence Interval | percentage of participants | 365 days post HCT |
|
|
|
| Secondary | Cumulative Incidence of Relapse | Incidence of primary disease relapse per standard definitions. | All participants. | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year post HCT |
|
|
|
| Secondary | Cumulative Incidence of Grade II-IV Acute GVHD by Day +100 | Acute GVHD will be graded per the 1995 consensus guidelines. | All participants. | Posted | Number | 95% Confidence Interval | percentage of participants | 100 days post HCT |
|
|
|
| Secondary | Cumulative Incidence of Chronic GVHD by Day +365 | Cumulative incidence of chronic GVHD by day +365 per NIH Consensus criteria. | All participants. | Posted | Number | 95% Confidence Interval | percentage of participants | 365 days post HCT |
|
|
|
| Secondary | Incidence of Non-relapse Death | Incidence of Non-relapse death/Transplant-related mortality. Non-relapse death is defined as death in continuous remission from primary disease requiring transplantation. | All participants. | Posted | Number | 95% Confidence Interval | percentage of participants | 365 days post HCT |
|
|
|
| Secondary | Incidence of Unexpected or Serious Adverse Events (AEs) | Grade 3-5 unexpected or serious adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.03) were captured up to day +130 or 30 days after the last dose of IL-2. Events listed, with causality in relation to study treatment noted. | All participants. | Posted | Number | adverse events | Up to days 130 post HCT |
|
|
|
| Secondary | Proportion of Treg Among Blood CD4+ T Cells at Day +90 After HCT | The proportion of Tregs to non-Treg CD4+ cells to be assessed at day +90. Natural Killer Cells (NKs): Median K/uL NK cells. | All participants. | Posted | Median | Full Range | K/uL NK cells | 90 days post HCT |
|
|
|
| Secondary | STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 30 | Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +30. | All participants. | Posted | Median | Full Range | percentage in total CD4s | 30 days post HCT |
|
|
|
| Secondary | STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 90 | Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +90. | All participants. | Posted | Median | Full Range | percentage in total CD4s | 90 days post HCT |
|
|
|
| Other Pre-specified | Function of Blood Treg After Allogeneic HSCT | Percent of Treg suppression at day +30. Investigators had also planned to test Treg function at day +90, if sufficient Tregs had been available for analysis. | All evaluable participants at day +30. | Posted | Median | Standard Deviation | percentage of suppression | 30 days post HCT |
|
|
|
| Other Pre-specified | Rate of Natural Killer Cell (NK) Reconstitution | Investigators planned to monitor natural killer cell (NK) reconstitution. Standard immune deficiency flow cytometry panels (IDP) was to be drawn on days +90, +180, and +365 to evaluate NK reconstitution. Results of standard lab tests to be compared to compiled data at a later date | Lab test results to be compared to compiled data at a later date. | Posted | 365 days post HCT |
|
|
| 11 |
| 20 |
| 4 |
| 20 |
| Atrial fibrillation | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Colonic hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Fever | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hepatobiliary disorders - Other, VOD | Hepatobiliary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Portal vein thrombosis | Hepatobiliary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Infections and infestations - Other, pneumonia | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Infections and infestations - Other, staphylococcus epidermis bacteremia | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Intracranial hemorrhage | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Cystitis non-infective | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Renal and urinary disorders - Other, adenovirus cystitis | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Renal and urinary disorders - Other, kidney stones | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hepatobiliary disorders - Other, portal vein thrombosis | Hepatobiliary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
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| D000602 |
| Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| Title | Measurements |
|---|---|
|
| GI bleed, unrelated |
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| Acute kidney injury, unrelated |
|
| Kidney stone, unrelated |
|
| Intracranial hemorrhage, unrelated |
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| Title |
|---|
| Measurements |
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| Measurements |
|---|
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