Phase I/II Study of Umbilical Cord Blood-derived Natural Killer Cells in Conjunction With High Dose Chemotherapy and Autologous Stem Cell Transplant for Patients With Multiple Myeloma
NK Cell Dose Levels:
If you choose to participate in this study, you will be assigned to a dose level of NK cells
based on when you joined this study. Up to 4 dose levels of NK cells will be tested. Three
(3) participants will be enrolled at each dose level until the highest tolerable dose level
is found. 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. When the highest tolerable dose is found, more participants may be
enrolled at that dose level.
Chemotherapy, NK and Autologous Cell Infusions:
In stem cell transplant, the days before you receive your stem cells are called minus days.
The day you receive the stem cells is called Day 0. The days after you receive the stem
cells are called plus days.
On Day -8, you will be admitted to the hospital and will receive hydration fluids by vein.
On Days -8 through -2, you will take lenalidomide by mouth 1 time a day.
On Day -7, you will receive melphalan by vein over about 30 minutes.
On Day -5 (+/-1 day), you will receive the NK cells by vein over about 1 hour.
From Day-5 to Day -1, depending on when you enter the study, some participants will receive
IL-2 daily as a subcutaneous (under the skin) injection. Your doctor will tell you if you
will be receiving this.
On Day 0, you will receive the stem cell transplant by vein over 30-60 minutes.
Starting on Day 0, you will receive filgrastim (G-CSF) through a needle under the skin 1
time a day every day until your white blood cell count begins to recover. Filgrastim is
designed to help cells in the bone marrow to multiply, which helps to raise white blood cell
counts more quickly, lower fever, and decrease the risk of infection.
You will receive antibiotics as standard of care to help prevent an infection.
You may receive lenalidomide, melphalan, NK cells, and/or the transplant as an outpatient,
if your study doctor approves.
Pregnancy Tests While Taking Lenalidomide Women who are able to become pregnant must have 3
negative pregnancy tests: within 10-14 days before lenalidomide is prescribed, within 24
hours before lenalidomide is prescribed, and about 28 days after the last lenalidomide dose.
You must fill the prescription within 7 days.
One (1) time a week for the first month you start taking lenalidomide, women who are able to
become pregnant will have blood (about 1 teaspoon) drawn for a pregnancy test. Then, in
females with regular menstrual cycles, blood (about 1 teaspoon) will be drawn for pregnancy
testing about 28 days after the last dose of lenalidomide. If menstrual cycles are
irregular, blood (about 1 teaspoon) will be drawn every 2 weeks, around 14 and 28 days after
the last dose of lenalidomide.
These blood tests will be part of a routine blood draw whenever possible.
Before you start treatment, the following tests/procedures will be performed if they were
not done as part of the routine pre-transplant procedure:
- You will have a bone marrow aspiration and biopsy to check the status of the disease.
To collect a bone marrow aspiration, 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
- You will have a series of x-rays (a bone survey) to check the status of the disease.
- Blood (about 2 tablespoons) and urine will be collected to check the status of the
- You will be asked about any symptoms you may be having.
Up to twice a week from Day -4 to Day +7, blood (about 2 tablespoons each time) will be
drawn to check for donor NK cells, if you are one of the first 12 participants enrolled in
this study. If donor NK cells are found, blood (about 2 tablespoons each time) will be
drawn 1 time each week until around Day +30 (+/-3 days). From 30 to about 100 days after
stem cell transplant, this blood will be drawn only if you had NK cells in your blood at the
last blood draw and you are having a routine follow-up visit.
At each visit after the NK cell infusion on Day -5, or as often as your study doctor thinks
it is needed, you will be checked for possible reactions to the transplant and study drugs,
including graft versus host disease (GVHD). GVHD is a condition in which transplanted
tissue attacks the body into which it is transplanted in patients receiving a stem cell
transplant. Graft failure occurs when transplanted stem cells may not be able to grow and
multiply in your body. If this happens, there will be a high risk of infections and/or
bleeding. If the number of white blood cells does not get back to high enough levels within
3 weeks after the transplant, more stem cells may need to be given.
Blood (about 2 teaspoons) will be drawn and urine will be collected for routine tests and to
check your kidney and liver function as often as your study doctor thinks it is needed.
About 30 after the stem cell transplant:
- Blood (about 4 tablespoons) will be drawn to check the status of the disease.
- Urine will be collected to check the status of the disease.
- If your study doctor thinks it is needed, you will have a bone marrow aspiration and
biopsy to check the status of the disease.
About 100 days after the stem cell transplant, blood (about 4 tablespoons) will be drawn and
urine will be collected to check the status of the disease.
Length of Study:
You will remain in this study 100 days after the stem cell transplant. Your participation
on this study will be over when you have completed this long-term follow-up visit.
You will be taken off study early if the disease gets worse, you have any infections,
intolerable side effects occur, you are not able to receive the stem cell transplant, you
need medical treatment not allowed in this study, your study doctor decides it is in your
best interest, you cannot keep appointments or take study drugs as instructed, or if you
decide that you want to leave the study early.
This is an investigational study. The way researchers make the NK cells is investigational.
At this time, it is being used in research only.
Lenalidomide is FDA approved and commercially available to treat patients with multiple
myeloma who have received at least 1 prior therapy.
IL-2 and melphalan are commercially available and FDA approved for the treatment of myeloma.
Up to 18 participants will be enrolled in this study. All will be enrolled at MD Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) of umbilical cord blood (UCB)-derived natural killer (NK) cells
Maximum tolerated dose (MTD) of UCB-derived NK cells defined as highest dose for which the probability of toxicity is closest to 20%. Dose limiting toxicity (DLT) defined as biopsy proven acute graft versus host disease (GvHD) with overall grade 3 as assessed based on modified Keystone criteria; failure to engraft; or grade 3-4 infusional toxicity of the NK cells.
Nina Shah, MD
UT MD Anderson Cancer Center
United States: Food and Drug Administration
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