Study of Individual Adult and Pediatric Patient Dose-escalated Interleukin-2 Therapy for Refractory Chronic Graft-versus-Host-Disease
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Individual Adult and Pediatric Patient Dose-escalated Interleukin-2 Therapy for Refractory Chronic Graft-versus-Host-Disease|
- Maximum Tolerated Dose (MTD) of 8-week Individual patient dose-escalated Interleukin-2 [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]Participants will be evaluated over the course of the 8-week treatment for Dose-Limiting Toxicities (DLTs) from the individual dose-escalated IL-2
- Overall cGVHD Clinical Response Rate [ Time Frame: Baseline, 8 Weeks ] [ Designated as safety issue: No ]Participants will have their cGVHD evaulated at baseline and at 8 weeks using the NIH Consensus criteria
- Overall Survival Rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Malignant Relapse Rate [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
|Study Start Date:||February 2015|
|Estimated Study Completion Date:||December 2020|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Interleukin-2 (IL-2)
Interleukin-2: Each participant will receive daily subcutaneous IL-2 for self-administration per cycle. Each participant will start at Dose Level A. In the abscence of DLTs or severe non-DLT adverse events, participants will have daily SC IL-2 dose-escalated at Week 2 (to dose level B) and at Week 4 (to Dose Level C), and continue on their maximum tolerated dose (MTD) IL-2 for 4 weeks total.
This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved IL-2 for the treatment of cGVHD but it has been approved for metastatic renal cell carcinoma (MCC), and metastatic melanoma.
Chronic GVHD is a medical condition that may occur after the participant has received bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize the participant's 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). Interleukin-2 (IL-2) is a natural protein involved with regulation of white blood cells (WBCs). WBCs are part of the immune system.The investigators looking to see whether IL-2 helps control chronic GVHD by stopping the donor's immune system from 'rejecting' the participant's body.
This study will look to see if increasing the dose level of study drug every two weeks can be administered safely without severe or unmanageable side effects in participants that have cGVHD. Depending on how well you tolerate your initial dose level and subsequent dose levels, your study drug dose level may be increased a maximum of two times. These increases in dose levels will occur two weeks apart. All participants on the study will start at the same dose level.
Study Drug: You will administer, or have someone else administer if you are unable to yourself, IL-2 through an injection under your skin. You should rotate the injection site, if possible. You will do this once every day for 8- weeks.
During the first 8 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 8 weeks of I L-2 therapy, your doctor may reduce the amount of steroids you take.
If your cGVHD improves after 8 weeks on dose-escalated 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 week 8. You will be re-assessed every 6 months while on extended duration IL-2 to determine if IL-2 therapy should continue, at the discretion of the treating physician.
Drug Diary: Each day of the first 8 weeks you take IL-2 and each day during extended-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 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 2 weeks for the first 8 weeks of IL-2 and at least every 8 weeks for extended duration IL-2.
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02318082
|Contact: John Koreth, DPhil, MBBS||(617) 632-2949||JKORETH@PARTNERS.ORG|
|United States, Massachusetts|
|Dana-Farber Cancer Insitute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: John Koreth, DPhil, MBBS 617-632-2949 email@example.com|
|Principal Investigator: John Koreth, MD|
|Principal Investigator:||John Koreth, DPhil, MBBS||Dana-Farber Cancer Institute|