Haploidentical Natural Killer (NK) Cells in Patients With Relapsed or Refractory Neuroblastoma
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|ClinicalTrials.gov Identifier: NCT00698009|
Recruitment Status : Terminated (Slow accrual.)
First Posted : June 16, 2008
Results First Posted : November 22, 2012
Last Update Posted : November 22, 2012
|First Submitted Date ICMJE||June 12, 2008|
|First Posted Date ICMJE||June 16, 2008|
|Results First Submitted Date ICMJE||October 23, 2012|
|Results First Posted Date ICMJE||November 22, 2012|
|Last Update Posted Date||November 22, 2012|
|Study Start Date ICMJE||June 2008|
|Actual Primary Completion Date||June 2012 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
||To find out if infusing your relative's NK cells into your body can be done safely. [ Time Frame: 1 Year ]|
|Change History||Complete list of historical versions of study NCT00698009 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE
||Researchers also want to find out if the infused cells will survive after the infusion, and if the NK cell infusion can help to destroy neuroblastoma cells. [ Time Frame: 1 Year ]|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Haploidentical Natural Killer (NK) Cells in Patients With Relapsed or Refractory Neuroblastoma|
|Official Title ICMJE||Study to Infuse Haploidentical Natural Killer Cells in Patients With Relapsed or Refractory Neuroblastoma|
Evaluate safety, feasibility, persistence, and anti-tumor effect of infused haploidentical donor-derived natural killer (NK) cells and low-dose interleukin-2 (IL-2).
NK cells are part of the immune system (the cells in the body that naturally fight disease and infection). NK cells can sometimes destroy tumor cells, and they may be better at destroying tumor cells when the NK cells are "mismatched" for certain proteins called human leukocyte antigens (HLA). This can be determined by looking at the donor's and the recipient's HLA types and by checking for other specialized proteins on the donor's NK cells (called killer immunoglobulin receptors [KIR]).
The NK cells will be collected from the donor's blood and then processed using an experimental device called a CliniMACS device. This device is designed to separate out the NK cells from the rest of the donor's collected white blood cells, using a special magnet. Before being infused into the recipient (you, if you choose to take part), the collected NK cells will be treated with a study drug called interleukin-2 (IL-2) in order to try to activate the NK cells' killing ability. You will also receive IL-2 injections to try to help the NK cells survive after infusion and possibly increase in number.
Within 28 days before you can start treatment on this study, you will have "screening tests" to help the study doctor decide if you are eligible to take part in this study. The following tests will be performed:
These screening tests would also need to be repeated before an additional NK cell infusion for this study, in order to see if you continue to be eligible to receive one. This will be described further below.
Identifying an Eligible Donor:
Your relative, who must share half of your HLA genes to be eligible for the study, will be tested to see if his or her KIR molecule has the "mismatch" that researchers believe should help the donor's NK cells to target the tumor cells in your body.
The donor's blood will also be tested to guard against the possibility of transmitting an infection to you during the NK cell infusion.
Samples of the donor's blood will be used to help researchers develop future tests that will be used to track how long the infused NK cells survive and function in recipients' bodies. In order to help track the cells after infusion, researchers prefer (but do not require) that if you are a female recipient, your donor should be male and if you are a male recipient, your donor should be female.
If you are found to be eligible to take part in this study, you will start the "conditioning" phase of this study within 4 weeks after the screening tests. Over the course of 6 days, you will receive chemotherapy with cyclophosphamide and fludarabine to weaken your immune system in order to help the survival of the infused NK cells, and then mesna to protect your bladder from side effects that cyclophosphamide may cause.
Cyclophosphamide, fludarabine, and mesna will preferably be infused through an indwelling catheter (a tube that remains in a vein, such as tunneled in the arm or through the chest). If you already have an indwelling catheter in place, you will not need to have a new one placed. If a new catheter is needed, however, you will be asked to sign a separate informed consent form for its placement.
The Conditioning schedule is the following:
-Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2, you will receive fludarabine by vein, over about 30 minutes.
On Days -5 and -4, you will receive cyclophosphamide by vein, over about 2 hours each time.
-Five times per day on Days -5 and -4, you will receive mesna by vein, over about 15 minutes each time.
Infusion of NK Cells:
On Day 0 you will receive the NK cells by vein, preferably through an indwelling catheter. The doctor will decide what amount of NK cells will be infused, which will affect how long the infusion lasts, but usually it lasts less than 1 hour.
To help prevent an allergic reaction to the infused cells (such as fever and chills), you will receive Benadryl (diphenhydramine) by vein, over 15-30 minutes, and Tylenol (acetaminophen) by mouth. You will also receive fluids by vein to help decrease the risk of kidney damage.
You or a caregiver will be trained in how to perform the IL-2 injections yourself. This drug will be injected under the skin for 9 doses over the course of 3 weeks.
If the doctor decides you are not eligible to receive the NK cell infusion on Day 0, you will be taken off study without receiving the donor's NK cells. The collected NK cells will be thrown away.
Blood Test for Measuring NK Cell Survival:
Blood (up to 4 teaspoons each time) will be drawn and tested to see how long the NK cells survive in your body. This blood will be drawn on Day 0 (before the NK cell infusion and again 2 hours later) and on Days 2, 7, 14, 21, and 28. (It is possible that this blood draw schedule will stop earlier if the disease gets worse or the infused NK cells can no longer be seen.)
Possible Additional NK Cell Infusion:
If the neuroblastoma responds and you did not suffer a new intolerable side effect from the NK cells, then you may be eligible to receive 1 additional infusion of NK cells. If so, the rest of the study procedures would be the same as before (the screening tests to determine your eligibility, the requirement that the donor still be eligible, the Conditioning Phase with chemotherapy, the IL-2 injections, and the blood tests). You must use the same donor as before, if he or she is still eligible.
So that you can be monitored for side effects, you will need to stay in the hospital from Day -6 until after the NK cell infusion (or longer if medically necessary).
After your final NK cell infusion, you will return for follow-up visits at least 3 times a week during the first 3 weeks. Then you will return for follow-up visits at around Day +28 and again 3 months after the last NK cell infusion. Following your 3 month visit, you will be asked to return for follow-up visits every 3 months up until one year after the last NK cell infusion. Below is a schedule of what will be done at each visit:
Day 28, at 3, 6, 9, and 12 months after infusion visits:
MIBG scan may be performed if your tumor was positive on MIBG scan in the past or if your doctor feels it is needed.
-Bone marrow biopsies/aspirations may be performed once in the first month, then may be done at each visit if you had neuroblastoma in your bone marrow at the time you started on the study or if your doctor feels it is necessary.
PET scan and/or bone scan may be performed sometime in Months 2 or 3, and again in months 6 -12 if your doctor feels it is needed.
This is an investigational study. Cyclophosphamide, fludarabine, mesna, and IL-2 are commercially available but not FDA approved for use in neuroblastoma. Injecting IL-2 under the skin is not FDA approved for use in increasing the production of NK cells. The CliniMACS device is not commercially available or FDA approved. Infusing NK cells in patients with neuroblastoma is also considered experimental. At this time and for this purpose, NK cell infusions and the CliniMACS device are being used in research only.
Up to 10 recipients and 10 donors will take part in this study. All will be enrolled at M. D. Anderson.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms ICMJE||Experimental: Fludarabine + Cyclophosphamide + NK Cell Infusion
Fludarabine 25 mg/m^2 intravenous (IV) Daily Over 30 minutes Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2. Cyclophosphamide 60 mg/kg IV Daily Over 2 Hours On Days -5 and -4. Natural Killer Cell Infusion on Day 0. Mesna 12 mg/kg By Vein, Over about 15 minutes, 5 Times Per Day on Days -5 and -4. Interleukin-2 subcutaneously three times weekly for 9 total doses following NK Cell Infusion.
|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||Terminated|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date ICMJE||June 2012|
|Actual Primary Completion Date||June 2012 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||Child, Adult, Older Adult|
|Accepts Healthy Volunteers ICMJE||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||NCT00698009|
|Other Study ID Numbers ICMJE||2006-0752|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||M.D. Anderson Cancer Center|
|Study Sponsor ICMJE||M.D. Anderson Cancer Center|
|Collaborators ICMJE||Not Provided|
|PRS Account||M.D. Anderson Cancer Center|
|Verification Date||October 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP