Trial of Regulatory T-cells Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease
|ClinicalTrials.gov Identifier: NCT01937468|
Recruitment Status : Active, not recruiting
First Posted : September 9, 2013
Last Update Posted : January 26, 2018
|First Submitted Date ICMJE||August 30, 2013|
|First Posted Date ICMJE||September 9, 2013|
|Last Update Posted Date||January 26, 2018|
|Start Date ICMJE||November 2013|
|Primary Completion Date||August 2017 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Adverse event profile and the maximum tolerate dose of Treg-enriched infusion plus 8-week low-dose IL-2 [ Time Frame: 24 weeks post Treg infusion, with continued follow-up for participants on extended duration IL-2 therapy. ]
Adverse events are considered dose-limiting toxicities by the criteria defined in protocol Section 6.2. If 1 or 0 out of 5 participants in the same dose-level cohort experience a DLT, escalation to the next dose level will take place. If this is dose-level C, then dose C is the MTD. If 2 or more participants out of 5 in the same dose level experience a DLT, then the previous dose-level will be the MTD. If this is dose-level A, accrual will stop.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01937468 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Trial of Regulatory T-cells Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease|
|Official Title ICMJE||A Phase I Trial of Regulatory T-cells Plus Low-Dose Interleukin-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease|
This research study is a Phase I clinical trial, which tests the safety of an investigational combination of IL-2 plus donor anti-inflammatory Treg cells and also tries to define the appropriate dose of the investigational combination of IL-2 plus donor anti-inflammatory Treg cells to use for further studies. IL-2 is involved with cell signaling and regulation of white blood cells (WBCs). WBCs are part of the immune system. Treg cells are also part of the immune system; they are involved with anti-inflammatory responses. "Investigational" means that the combination of IL-2 and anti-inflammatory Treg cell infusion is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved the combination of IL-2 and anti-inflammatory Treg cell infusion for use in people with cGVHD.
Chronic GVHD is a medical condition that may occur after you have received your bone marrow, stem cell or cord blood transplant from a donor. The donor's immune system may recognize your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host disease.
Traditional standard therapy to treat cGVHD is prednisone (steroids). Participants on this trial have not responded to steroid therapy. The investigators are looking to assess the safety and optimal dose for the combination of IL-2 plus donor anti-inflammatory Treg cells, that may help control cGVHD by stopping the donor's immune system from 'rejecting' your body.
After the screening procedures confirm that you are eligible to participate in the research study: If you take part in this research study, you (and your donor) will have the following tests and procedures:
Donor Lymphocytes Collection: Lymphocytes are a type of white blood cell involved with the immune system. Your original marrow/stem cell donor will undergo one white blood cell collection procedures called leukapheresis. Blood from the vein in one arm will be circulated through a special machine to remove the white blood cells, and the rest of the blood will be returned to the donor's other arm. The cells collected from the leukapheresis will be sent to the laboratory where the amount of white blood cells collected will be measured. A sample will be removed for study testing, and the remaining lymphocytes will be set-aside for infusion.
Donor Lymphocyte Processing: Once the lymphocytes are collected from your donor, the CliniMACS System device will enrich (preferentially select) the number of Treg cells. Samples will be taken before and after processing by the CliniMACS System to examine the cells. After completing the necessary safety tests, the Treg-enriched donor lymphocyte cells will be ready for administration.
Donor Cellular Infusion (DCI): The Treg-enriched donor lymphocytes will be infused through an intravenous (I.V.) catheter over approximately 5-10 minutes. Prior to the infusion, you will receive Tylenol and Benadryl to prevent transfusion related reactions. You will be observed for about 1 hour after the infusion. The total anticipated time you will spend in the clinic is approximately 2 hours.
Since the investigators are looking for the highest one-time dose of the anti-inflammatory donor cells that can be administered safely in combination with IL-2 without severe or unmanageable side effects in participants that have cGVHD, not everyone who participates in this research study will receive the same dose of the donor cells. The cell dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their cell doses.
Study Drug: You will give yourself or be given IL-2 daily through an injection under your skin. You will do this once every day for 8 weeks, starting from the day of donor Treg cell infusion. You will then have 4 weeks off of IL-2.
IL-2 will be provided in single-use (one-time only) syringes to be refrigerated at home at 36 - 46°F (2 - 8°C).
During the first 6 weeks of IL-2, you will continue to take steroids and other immune suppressing medications 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.
If your cGVHD improves after 8 weeks on IL-2, you may have the option of continuing extended-duration therapy. Extended-duration therapy is daily IL-2 treatment starting at the end-of-study visit after week 12. Your doctor will discuss this option with you. If you continue with extended-duration IL-2 therapy after completing the week 12 evaluation, you will be assessed on the following schedule:
Drug Diary: Each day for the first 8 weeks you take IL-2 and each day during extend-duration IL-2 (if applicable), you will be asked to document, in a drug diary, when you took the drug and where you injected it. The diary will also include special instructions for taking the study drug(s). The diary will also ask if the entire syringe was injected, and if there were other issues related to IL-2. You will be asked to return your drug diary to clinic every 14 days while you receive IL-2. If you continue taking IL-2 in the extend-duration portion, you will return your drug diary every 8 weeks (at your clinic visit).
Chronic GVHD Assessments: 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 (for example, whether you have experienced any nausea, vomiting, diarrhea, difficulty swallowing). The investigators will also look at the range of motion of different body parts (for example, your arms).
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms||Experimental: Treg-enriched infusion plus 8-week low-dose Interleukin-2
Treg-enriched Cell Dose: Participants will be targeted to a defined dose of donor Treg-enriched total nucleated cells. Initial enrollment will be at target dose-level A. Subsequent cohorts will be dose escalated/de-escalated per the schema. Interleukin-2: Starting the day of Treg-enriched cell infusion, each participant will receive daily subcutaneous IL-2 for self-administration for 8 weeks, followed by a 4-week hiatus. IL-2 will be administered on an outpatient basis. Expected toxicities and potential risks as well as dose modifications are described in Section 6 (Expected Toxicities and Dosing Delays/Dose Modification).
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Estimated Completion Date||November 2020|
|Primary Completion Date||August 2017 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01937468|
|Other Study ID Numbers ICMJE||13-281
R01CA183559-01 ( U.S. NIH Grant/Contract )
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||John Koreth, MD, Dana-Farber Cancer Institute|
|Study Sponsor ICMJE||Dana-Farber Cancer Institute|
|PRS Account||Dana-Farber Cancer Institute|
|Verification Date||January 2018|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP