Haploidentical Natural Killer (NK) Cells With Epratuzumab for Relapsed Acute Lymphoblastic Leukemia (ALL)
|First Received Date ICMJE||July 16, 2009|
|Last Updated Date||May 19, 2014|
|Start Date ICMJE||July 2009|
|Primary Completion Date||May 2012 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Time to Progression (TTP) [ Time Frame: 1 Year ]
TTP calculated as average time, in months, from baseline to participants disease progression or death, monitored for a minimum of 1 year
|Original Primary Outcome Measures ICMJE
||Time to Progression (TTP) and Overall Survival (OS) [ Time Frame: 1 Year ]|
|Change History||Complete list of historical versions of study NCT00941928 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Overall Survival (OS) [ Time Frame: Minimum of 1 year, or until disease progression or death ]
Number of surviving participants without disease progression or death for any reason at one year post treatment.
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Haploidentical Natural Killer (NK) Cells With Epratuzumab for Relapsed Acute Lymphoblastic Leukemia (ALL)|
|Official Title ICMJE||Adoptive Transfer of Haploidentical NK Cells in Combination With Epratuzumab for the Treatment of Relapsed Acute Lymphoblastic Leukemia|
The goal of this clinical research study is to learn if transferring the donor's NK cells, in combination with an antibody called epratuzumab and low-dose interleukin (IL-2), into your body can be done safely. Researchers want to find out if the infused NK cells will survive after the infusion and if the NK cell infusion helps to destroy cancer cells in the recipient's body and possibly to help control the disease.
· Evaluate the feasibility of collecting an adequate number of natural killer (NK) cells from a donor and evaluate the safety of a haploidentical donor-derived NK cell infusion, Epratuzumab, and low-dose interleukin-2 (IL-2).
Epratuzumab is designed to attach to certain proteins on the surface of ALL cells. This may cause the cancer cells to die.
Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth. This may cause the cancer cells to die.
Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.
IL-2 is designed to help NK cells live longer and work better.
NK cells are the cells in the body that fight disease and infection. NK cells may destroy tumor cells, particularly when the NK cells are "mismatched" for certain proteins, called human leukocyte antigens (HLA). Researchers think that this ability to destroy tumor cells can be predicted by learning the donor's and the recipient's HLA types to see if they are a mismatch, and by checking for other specialized proteins found on the surface of the donor's NK cells. These proteins are called killer immunoglobulin receptors (KIR).
The NK cells will be collected from the donor's blood and then processed in a lab at M. D. Anderson, where researchers will use a machine, called a CliniMACS device, to separate out the NK cells from the rest of the donor's collected white blood cells and treat them overnight with a drug called IL-2. This is done to make the NK cells stronger before they are given to the recipient. You will also receive IL-2 injections under your skin to try to help the NK cells survive longer and to possibly increase the number of NK cells in your body after the infusion.
Before you can start treatment on this study, you will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:
These screening tests, except for the HLA and KIR-typing, would also need to be repeated before an additional leukapheresis procedure can be done as a part of this study, in order to see if you continue to be eligible to have another one performed.
Identifying an Eligible Donor:
Your relative will be tested to see if his or her KIR has a type of "mismatch" that researchers think will help the donor's NK cells target the cancer cells in your body. They must also share half of your HLA genes to be eligible to take part in this study.
The donor's blood will also be checked for infections, such as HIV, to protect against the possibility of transmitting an infection to you during the NK cell infusion.
To help track the NK cells after infusion, researchers prefer (but do not require) that if you are a female recipient, your donor is male and if you are a male recipient, your donor is female.
If you and the donor are found to be eligible to take part in this study, on Day -4 (4 days before the NK cell infusion) and Day -1 (1 day before the NK cell infusion), you will have an epratuzumab infusion. The length of time this infusion will take will be different for each patient. This will be done using an indwelling catheter (a tube that remains in a vein, such as tunneled in the arm or through the chest to continuously inject or drain a part of your body). If you already have an indwelling catheter in place, you will not need to have a new one placed. However, if a new catheter is needed, you will be asked to sign a separate informed consent form for its placement.
On Day -1 (1 day before the NK cell infusion) and on Days 3, 6, 10, 13, and 17, you will receive an epratuzumab infusion. This will take several hours.
This phase will start within 28 days after the screening tests. During this phase, you will receive chemotherapy with cyclophosphamide and fludarabine to weaken your immune system in order to help the infused NK cells survive. You will stay in the hospital from Day -6 until after the NK cell infusion or longer if the doctor thinks it is necessary.
On Day -6 through Day -2, you will receive fludarabine 1 time each day by vein, over about 30 minutes each time.
On Days -5 and -4, you will receive cyclophosphamide 1 time each day by vein, over about 2 hours each time.
On Days -5 and -4, you will receive mesna 5 times per day by vein, over about 15 minutes each time. Mesna is given to protect your bladder from side effects that may be caused by cyclophosphamide.
Cyclophosphamide, fludarabine, and mesna will all be infused through the same indwelling catheter.
Infusion of NK cells:
On Day 0, you will receive the NK cells by vein, preferably through an indwelling catheter. If you do not have an indwelling catheter, you may receive the infusion intravenously (IV -- by vein). The doctor will decide the amount of NK cells to be infused, which will affect how long the infusion lasts. Usually the infusion should last less than 1 hour.
To help prevent an allergic reaction to the infused NK 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. If the study doctor thinks it is necessary, you may also receive a steroid to help prevent side effects.
If the doctor thinks that 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.
This study allows eligible recipients under the age of 2 years of age to participate. You and/or a caregiver will be trained how to give the IL-2 injections to yourself. This drug will be injected under the skin for 9 doses. You will take 3 doses per week over a 3-week period after receiving the NK cells.
Measuring NK Cell Survival Through Blood Test:
On Day 0 (before the NK cell infusion and again 2 hours later), and 1 time on each of the following days: Days 2, 7, 14, 21, and 28, blood (about 4 teaspoons each time) will be drawn and tested to see how long the NK cells survive in your body.
If the disease gets worse or the infused NK cells can no longer be seen, this blood draw schedule may be stopped early.
You will have follow-up visits at least 3 times per week during the first 3 weeks, and then 1 time about 28 days after your NK cell infusion. Then, you will have additional follow-up visits at about Months 2 and 3. At these visits, the following tests and procedures will be performed:
On Days 14 and 28, and during Months 2 and 3, you will have a bone marrow biopsy and/or aspiration.
Length of Study:
You will remain on active study for up to 3 months following your NK cell infusion that you agree to have performed.
This is an investigational study. Cyclophosphamide, fludarabine, mesna, and IL-2 are FDA approved and commercially available. Cyclophosphamide and fludarabine are approved for treating leukemia in adults. IL-2 is FDA-approved, but not for the treatment of leukemia.
Epratuzumab is not FDA approved or commercially available. It is only being used in research.
The use of the CliniMACS machine and infusing NK cells combined with epratuzumab in patients with ALL are only being done in research.
Up to 10 recipients and 10 donors will take part in this study. All will be enrolled at The University of Texas (UT) MD Anderson Cancer Center.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Study Arms||Experimental: Haploidentical NK cells + Epratuzumab
Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours. Mesna 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.
|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|
|Completion Date||May 2012|
|Primary Completion Date||May 2012 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||Child, 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||NCT00941928|
|Other Study ID Numbers ICMJE||2007-0160|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|Plan to Share Data||Not Provided|
|IPD Description||Not Provided|
|Responsible Party||M.D. Anderson Cancer Center|
|Study Sponsor ICMJE||M.D. Anderson Cancer Center|
|Collaborators ICMJE||Not Provided|
|Information Provided By||M.D. Anderson Cancer Center|
|Verification Date||May 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP