Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02280525 |
| Other study ID # |
2014-0297 |
| Secondary ID |
P-TRP-1996-14NCI |
| Status |
Completed |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
March 5, 2015 |
| Est. completion date |
July 9, 2019 |
Study information
| Verified date |
June 2023 |
| Source |
M.D. Anderson Cancer Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The goal of this clinical research study is to find the highest tolerable dose of immune
cells called natural killer (NK) cells that can be given with chemotherapy to patients with
CLL. Researchers want to learn if adding NK cells will be effective in treating the disease.
The safety of this will also be studied.
NK cells may kill cancer cells that remain in your body after your last chemotherapy
treatment. The NK cells will be separated from umbilical cord blood. The device used in the
laboratory to separate the NK cells is called a CliniMACS. These separated NK cells will then
be grown in the lab to increase the number of NK cells that can be given to you by vein.
This is an investigational study. Rituximab, fludarabine, and cyclophosphamide are FDA
approved and commercially available for the treatment of CLL. Cytarabine, filgrastim, and
lenalidomide are FDA approved and commercially available for the treatment of other types of
cancer. The use of cytarabine, filgrastim, and lenalidomide for the treatment of CLL is
investigational.
The use of NK cells is investigational. The NK cell process is not FDA approved or
commercially available. It is currently being used for research purposes only.
Up to 44 patients will take part in this study. All will be enrolled at MD Anderson.
Description:
Central Venous Catheter:
The chemotherapy, some of the other drugs in this study, and the NK cells will be given by
vein through your central venous catheter (CVC). A CVC is a sterile flexible tube and needle
that will be placed into a large vein while you are under local anesthesia. Blood samples
will also be drawn through your CVC. The CVC will remain in your body during treatment. Your
doctor will explain this procedure to you in more detail, and you will be required to sign a
separate consent form.
NK Cell Dose Levels:
You will be assigned to a dose level of NK cells based on when you joined this study. Up to 5
dose levels of NK cells will be tested. The first group of participants will receive the
lowest dose level. Each new group will receive a higher dose than the group before it, if no
intolerable side effects were seen. This will continue until the highest tolerable dose of NK
cells is found.
If not enough NK cells can be produced in the laboratory for your assigned dose level, you
will still receive the NK cells that were produced. If you are infused with a lower number of
NK cells than had been originally planned, the CLL may not respond. Researchers do not know
what number of NK cells is needed for a response.
Chemotherapy and NK Cell infusion:
The days before you receive the NK cells are called minus days. The day you receive the NK
cells is called Day 0. The days after you receive the NK cells are called plus days.
You will receive 1 of 3 study drug plans. Your doctor will decide which plan you will receive
based on your age, prior treatment, diagnosis, and health status. You will receive 1 of the 3
options as explained below.
Option #1:
On Day -2 through Day +14, you will take lenalidomide by mouth once a day at about the same
time each day. If you are able to do so, you will take aspirin or another drug as instructed
by your doctor on these days to help prevent blood clots. You will be asked to complete a
study drug diary and bring it to each study visit. The study staff will tell you more about
this.
On Day -5, you will receive fludarabine by vein over 1 hour and cyclophosphamide by vein over
3 hours. If you have a B-cell cancer, you will receive rituximab by vein over 3-6 hours.
Rituximab and fludarabine are given to treat the cancer and lower the immune system in order
to lower the risk of the body rejecting the NK cells. Cyclophosphamide is given to lower the
immune system in order to lower the risk of graft-versus-host disease (GVHD -- when
transplanted immune tissue, such as cord blood NK cells, attacks the tissues of the
recipient's body).
On Day -4 and -3, you will receive fludarabine by vein over 1 hour and cyclophosphamide by
vein over 3 hours.
On Days -2 and -1, you will rest.
On Day 0, you will receive NK cells by vein.
Option #2:
On Day -2 through Day +14, you will take lenalidomide by mouth once a day at about the same
time each day. If you are able to do so, you will take aspirin or another drug as instructed
by your doctor on these days to help prevent blood clots. You will be asked to complete a
study drug diary and bring it to each study visit. The study staff will tell you more about
this.
On Day -6, you will receive fludarabine by vein over 1 hour. Fludarabine is given to treat
the cancer and lower the immune system in order to lower the risk of the body rejecting the
NK cells.
On Day -5, and -4, you will receive fludarabine by vein over 1 hour and cyclophosphamide by
vein over 3 hours. Cyclophosphamide is given to lower the immune system in order to lower the
risk of graft-versus-host disease (GVHD -- when transplanted immune tissue, such as cord
blood NK cells, attacks the tissues of the recipient's body).
On Day -3 and -2, you will receive fludarabine by vein over 1 hour. Fludarabine is given to
treat the cancer and lower the immune system in order to lower the risk of the body rejecting
the NK cells.
On Day -1, you will rest.
On Day 0, you will receive NK cells by vein.
Option #3:
On Day -7, you be given fluids by vein to hydrate you.
On Days -6 through - 2, you will receive fludarabine by vein over 1 hour and cytarabine by
vein over 1 hour.
On Day -2 through Day +14, you will take lenalidomide by mouth once a day at about the same
time each day. If you are able to do so, you will take aspirin or another drug as instructed
by your doctor on these days to help prevent blood clots. You will be asked to complete a
study drug diary and bring it to each study visit. The study staff will tell you more about
this.
On Day -1, you will rest.
On Day 0, you will receive NK cells by vein.
Starting on Day +5, you will receive filgrastim as an injection under the skin 1 time a day
until your blood cell levels return to normal. Filgrastim is designed to help with the growth
of white blood cells.
Study Visits:
Within 7 days before starting chemotherapy:
- You will have a physical exam.
- Blood (about 2 tablespoons) will be drawn for routine tests.
Within 2 days and then about 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, and 4
months after the NK cell infusion, the following tests and procedures will be performed:
°Blood (about 4 tablespoons) will be drawn for routine tests, tests to measure levels of
certain proteins, to learn how your body's immune system responds to the NK cell infusion,
and to check the level of the NK cells.
About 1 week, 3 weeks, 1 month, and 4 months after the NK cell infusion, you will have a bone
marrow biopsy/aspiration to check the status of the disease. To collect a bone marrow
biopsy/aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small
amount of bone and bone marrow is withdrawn through a large needle.
Pregnancy Tests:
If you can become pregnant, blood (about 1 teaspoon each time) will be drawn for a pregnancy
test within 10-14 days and 24 hours before you are prescribed lenalidomide, at about Day +21,
at 2 months after NK cell infusion, and then again 4 weeks after therapy is stopped. To
continue on this study, you must not be pregnant.
If possible, the blood needed for pregnancy tests will be collected during the above blood
draws so that no additional needle sticks will be needed.
Length of Study:
You will be on study for up to about 1 year. You may be taken off study early if the disease
gets worse, if you are unable to receive the NK cell infusion, if you have any intolerable
side effects, if you are unable to follow study directions, if your doctor thinks it is in
your best interest, if the study is stopped, or if you choose to leave the study early.
You should talk to the study doctor if you want to leave the study early. If you are taken
off study early, you still may need to return for routine post-transplant follow-up visits,
if your doctor decides it is needed.
If you are thinking about dropping out of this study, please tell the study doctor. The
doctor can tell you about the effects of stopping treatment. You and the doctor can talk
about what follow-up care and testing would help you the most.
If you leave the study, your test results and information cannot be removed from the study
records.
