Hematologic DiseasesPhase 1NCT01445561
Ultra Low Dose Interleukin-2 in Healthy Volunteers
A Phase 1 study testing Interleukin-2 (100,00 IU/m(2) SQ) in people with Hematologic Diseases, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Interleukin-2 is a drug that can help stimulate the body s response to inflammation. High dose interleukin-2 has been used to treat different types of cancer and immune system disorders. However, it can cause frequent and often serious side effects at the doses currently used for treatment. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hematologic Diseases
- What is being tested?
- Interleukin-2 (100,00 IU/m(2) SQ)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Sep 2011to 15 Jul 2013
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Healthy volunteers confirmed by brief history and physical examination and blood work through the CHI screening protocol
- Males or females ages 18 years or older
Who cannot join
- History of inflammatory or autoimmune disease
- History of inflammatory or autoimmune disease in first degree relatives
- History of malignancies
- Recipients of hematopoietic stem cell transplant or solid organ transplant
- History of seizures
- Positive HIV, hepatitis B surface antigen or hepatitis C antibody
Show all 24Show fewer
- History or clinical signs of cardiac disease including coronary artery disease, cardiac arrhythmia, congestive heart failure
- History or clinical signs of of pulmonary disease including obstructive lung disease and asthma
- Active infections requiring systemic antibiotic therapy or anti-viral therapy
- History of systemic fungal or mycobacterial infections
- Use of immune modifying medications, i.e.- non steroidal anti-inflammatory drugs (aspirin, ibuprofen, naproxen, celecoxib, ketrolac), steroid (prednisone, dexamethasone, hydrocortisone), chemotherapy (cisplatin, dacarbazine, interferon alpha, tamoxifen)
- Persons who are alcoholic or abusers of illicit drugs
- Female subjects who are or may be pregnant or lactating
- Psychiatric diagnoses or symptoms, to include hypomania, bipolar disorder, major depression, or dysthymia
- Abnormal or marginal peripheral blood count that in the opinion of the PI will cause Hemoglobin and Hematocrit levels to drop as a result of participation in this study
- Liver function tests above the normal laboratory reference range
- Renal function test above the normal laboratory reference range
- Contraindication to interleukin-2 (i.e. hypersensitivity to IL- 2 products, active coronary artery disease, patients with organ allograft)
- Recent recipient of any type of vaccination (i.e. rotavirus vaccine, BCG, influenza virus vaccine, rubella virus vaccine, mumps virus vaccine, measles vaccine, poliovirus vaccine, smallpox vaccine, typhoid vaccine, varicella virus vaccine, yellow fever vaccine) in the 4 weeks preceding and during active study participation
- Body mass index greater than 35
- Inability to comprehend the investigational nature of the study or provide informed consent
- Diabetes mellitus or fasting blood glucose of > 100 mg/dL.
- Any drugs or supplements that interfere with blood clotting such as Vit.E, NSAIDS, Warfarin (Coumadin), ticlopidine (Ticlid), clopidogrel (Plavix)
- Use of iodinated contrast media in the 4 weeks preceding and during active study participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Safety and the Tolerability of Ultra Low Dose Interleukin-2 in Healthy Volunteers
Background:
- Interleukin-2 is a drug that can help stimulate the body s response to inflammation. High dose interleukin-2 has been used to treat different types of cancer and immune system disorders. However, it can cause frequent and often serious side effects at the doses currently used for treatment. Very low dose interleukin-2 (700 folds less than regular dose) was previously tested in cancer patients and stem cell transplant recipients. The study observed important immune changes and minimal side effects in those patients. Researchers want to test the healthy immune system's responses to very low doses of interleukin-2 to better understand how the drug works.
Read more
Objectives:
- To study the effects of very low doses of interleukin-2 on healthy volunteers.
Eligibility:
- Healthy volunteers at least 18 years of age.
Design:
- Participants will be screened with a medical history and physical exam. They will also have blood and urine samples.
- Participants will receive one of two possible very low doses of interleukin-2 every day for 5 days.
- Blood samples will be taken twice before the first dose, 1 day after the first dose, and before the next three doses. Followup blood samples will be taken on Days 7, 14, and 28 after the first dose.
Read the detailed description
Interleukin 2 (IL-2, aldesleukin) was discovered as a T cell growth factor more than 30 years ago. IL-2 was the first human cytokine used therapeutically. IL-2 induces antigen specific T cells, and two important lymphocyte subsets: regulatory T cells (T-regs) and natural killer cells (NK) cells. T-regs have a critical role in self-tolerance and pathogenesis of autoimmune disease or graft versus host disease (GVHD), and they have been extensively studied in solid tumors, hematologic malignancies, viral hepatitis, and HIV infections. NK cells have a unique role in bridging innate and adaptive immunity. NK cells facilitate hematopoietic stem cell (HSC) engraftment reduce GVHD and increase graft-versus-leukemia (GVL) effects. NK cells have important roles on pathogenesis of malignancies, autoimmune disease and AIDS. Conventional dose IL-2 treatment promotes marked expansion of regulatory T cells, and NK cells but is associated with significant side effects. However, much lower doses of interleukin-2 (0.5- 1MIU/m2/day) which lack significant side effects, also induce expansion of T regs and NK cells. These observations suggest that ultra low dose IL-2 would be safe and appropriate to give to hematopoietic stem cell donors. The quality of the transplant would be improved because the higher dose of T-regs would reduce the risk of GVHD while the higher NK cells would augment the GVL effect. The aim of this study is to evaluate the safety and the tolerability of ultra low dose IL-2 in healthy volunteer for preferential expansion of T-regs and NK cells with a view to extending ultra low dose IL-2 administration to stem cell donors. We anticipate that this study will provide valuable information on the biology of IL-2 on the human immunome applicable to various human disease conditions, including cancer, immunodeficiency disease, autoimmune disease, and hematopoietic stem cell transplantation. The proposed IL-2 dose is 2-3 logs lower than the manufacturer s recommended dose. We therefore expect that the dose used in this protocol will be well tolerated. Nevertheless, because there is little information on the tolerability and safety of IL-2 at these ultra low doses, we have structured this study as a safety protocol with stopping rules for unacceptable side effects. This is important because we hope to use the safety data generated to justify a future protocol giving ultra low dose IL-2 to stem cell donors.
- Conditions
- Hematologic Diseases
- Being tested
- Interleukin-2 (100,00 IU/m(2) SQ)
- Keywords
- Interleukin-2, IL-2, Stem Cells, Regulatory T Cells (T regs), Natural Killer Cells (NK cells), Healthy Volunteer, HV
- Medical subject headings
- Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interleukin-2 (100,00 IU/m(2) SQ)Drug
100,000 International Units/m2 SQ daily for 5 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 100,000 international units/m2 SQ daily for 5 days Receives: Drug: Interleukin-2 (100,00 IU/m(2) SQ) |
| 2 | Experimental | 200,000 international units/m2 SQ daily for 5 days Receives: Drug: Interleukin-2 (100,00 IU/m(2) SQ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of ultra low dose IL-2. TRSAE rate of no more than 5% would allow us to proceed with future studies.
To determine the safety and the tolerability of ultra low dose (physiologic dose) interleukin-2 in healthy volunteers
Measured: 28 days
Secondary outcomes (1)
Human immune response (immunome) to ultra low dose IL-2 based on research lab assessments
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2011 (estimated)
- Study start28 Sep 2011
- Primary completion15 Jul 2013
- Study completion15 Jul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hematologic DiseasesStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Chen Zhao, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01445561
- Sponsor's protocol ID
- 110268
- Other IDs
- 11-H-0268
- Status last verified
- Mar 2020
- First submitted
- 30 Sep 2011
- Last updated
- 16 Mar 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Smith KA. Interleukin-2: inception, impact, and implications. Science. 1988 May 27;240(4856):1169-76. doi: 10.1126/science.3131876.
PubMed 3131876Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007-8. doi: 10.1126/science.181845.
PubMed 181845Macdonald D, Jiang YZ, Gordon AA, Mahendra P, Oskam R, Palmer PA, Franks CR, Barrett AJ. Recombinant interleukin 2 for acute myeloid leukaemia in first complete remission: a pilot study. Leuk Res. 1990;14(11-12):967-73. doi: 10.1016/0145-2126(90)90109-m.
PubMed 2280612
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and the Tolerability of Ultra Low Dose Interleukin-2 in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01445561
- Acronym / sponsor ID
- 110268
- Conditions
- Hematologic Diseases
- Keywords
- Interleukin-2, IL-2, Stem Cells, Regulatory T Cells (T regs), Natural Killer Cells (NK cells), Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 28 Sep 2011 (actual)
- Primary completion
- 15 Jul 2013 (actual)
- Study completion
- 15 Jul 2013 (actual)
- First posted
- 3 Oct 2011 (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.
Background:
- Interleukin-2 is a drug that can help stimulate the body s response to inflammation. High dose interleukin-2 has been used to treat different types of cancer and immune system disorders. However, it can cause frequent and often serious side effects at the doses currently used for treatment. Very low dose interleukin-2 (700 folds less than regular dose) was previously tested in cancer patients and stem cell transplant recipients. The study observed important immune changes and minimal side effects in those patients. Researchers want to test the healthy immune system's responses to very low doses of interleukin-2 to better understand how the drug works.
Objectives:
- To study the effects of very low doses of interleukin-2 on healthy volunteers.
Eligibility:
- Healthy volunteers at least 18 years of age.
Design:
- Participants will be screened with a medical history and physical exam. They will also have blood and urine samples.
- Participants will receive one of two possible very low doses of interleukin-2 every day for 5 days.
- Blood samples will be taken twice before the first dose, 1 day after the first dose, and before the next three doses. Followup blood samples will be taken on Days 7, 14, and 28 after the first dose.
Detailed description
Interleukin 2 (IL-2, aldesleukin) was discovered as a T cell growth factor more than 30 years ago. IL-2 was the first human cytokine used therapeutically. IL-2 induces antigen specific T cells, and two important lymphocyte subsets: regulatory T cells (T-regs) and natural killer cells (NK) cells. T-regs have a critical role in self-tolerance and pathogenesis of autoimmune disease or graft versus host disease (GVHD), and they have been extensively studied in solid tumors, hematologic malignancies, viral hepatitis, and HIV infections. NK cells have a unique role in bridging innate and adaptive immunity. NK cells facilitate hematopoietic stem cell (HSC) engraftment reduce GVHD and increase graft-versus-leukemia (GVL) effects. NK cells have important roles on pathogenesis of malignancies, autoimmune disease and AIDS. Conventional dose IL-2 treatment promotes marked expansion of regulatory T cells, and NK cells but is associated with significant side effects. However, much lower doses of interleukin-2 (0.5- 1MIU/m2/day) which lack significant side effects, also induce expansion of T regs and NK cells. These observations suggest that ultra low dose IL-2 would be safe and appropriate to give to hematopoietic stem cell donors. The quality of the transplant would be improved because the higher dose of T-regs would reduce the risk of GVHD while the higher NK cells would augment the GVL effect. The aim of this study is to evaluate the safety and the tolerability of ultra low dose IL-2 in healthy volunteer for preferential expansion of T-regs and NK cells with a view to extending ultra low dose IL-2 administration to stem cell donors. We anticipate that this study will provide valuable information on the biology of IL-2 on the human immunome applicable to various human disease conditions, including cancer, immunodeficiency disease, autoimmune disease, and hematopoietic stem cell transplantation. The proposed IL-2 dose is 2-3 logs lower than the manufacturer s recommended dose. We therefore expect that the dose used in this protocol will be well tolerated. Nevertheless, because there is little information on the tolerability and safety of IL-2 at these ultra low doses, we have structured this study as a safety protocol with stopping rules for unacceptable side effects. This is important because we hope to use the safety data generated to justify a future protocol giving ultra low dose IL-2 to stem cell donors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Interleukin-2 (100,00 IU/m(2) SQ)100,000 international units/m2 SQ daily for 5 days |
| 2 | Experimental | Drug: Interleukin-2 (100,00 IU/m(2) SQ)200,000 international units/m2 SQ daily for 5 days |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy volunteers confirmed by brief history and physical examination and blood work through the CHI screening protocol
- Males or females ages 18 years or older
Key exclusion criteria (24 listed)
- History of inflammatory or autoimmune disease
- History of inflammatory or autoimmune disease in first degree relatives
- History of malignancies
- Recipients of hematopoietic stem cell transplant or solid organ transplant
- History of seizures
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-2 (100,00 IU/m(2) SQ)100,000 International Units/m2 SQ daily for 5 days | Drug | 1, 2 |
Primary outcome
Safety and tolerability of ultra low dose IL-2. TRSAE rate of no more than 5% would allow us to proceed with future studies.
Time frame: 28 days
To determine the safety and the tolerability of ultra low dose (physiologic dose) interleukin-2 in healthy volunteers
1 secondary outcome
Human immune response (immunome) to ultra low dose IL-2 based on research lab assessments
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2020.
- Background: PubMed 3131876Smith KA. Interleukin-2: inception, impact, and implications. Science. 1988 May 27;240(4856):1169-76. doi: 10.1126/science.3131876.
- Background: PubMed 181845Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007-8. doi: 10.1126/science.181845.
- Background: PubMed 2280612Macdonald D, Jiang YZ, Gordon AA, Mahendra P, Oskam R, Palmer PA, Franks CR, Barrett AJ. Recombinant interleukin 2 for acute myeloid leukaemia in first complete remission: a pilot study. Leuk Res. 1990;14(11-12):967-73. doi: 10.1016/0145-2126(90)90109-m.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Chen Zhao, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
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 (100,00 IU/m(2) SQ) in people with Hematologic Diseases, run by National Heart, Lung, and Blood Institute (NHLBI) 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 2 inclusion and 24 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 16 Mar 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability of ultra low dose IL-2. TRSAE rate of no more than 5% would allow us to proceed with future studies. (time frame: 28 days). 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 NCT01445561, which also lists 3 linked publications.
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 16 Mar 2020.