Natural Killer Cells In Allogeneic Cord Blood Transplantation
18 Years
59 Years
Both
Leukemia, Chronic Lymphocytic Leukemia
Trial Information
Natural Killer Cells In Allogeneic Cord Blood Transplantation
Study Drug Administration and Study Procedures:
Two (2) UCB units have been selected to give to you. If you are enrolled after the third
patient is enrolled, one of the selected units will have NK cells separated out from it.
The NK cells are separated from the UCB unit using a machine called the CliniMACS system.
This machine uses certain kinds of cells and antibody-coated magnetic beads to separate the
NK cells. The separated NK cells will then be "grown" to increase their numbers before they
are given to you. The drug aldesleukin (interleukin-2) will be added to the NK cells in
attempt to improve their function. The aldesleukin will be washed out of the NK cells before
they are given to you. The second UCB unit will be given to you without any NK cell
separation.
For UCB transplant schedules, the days before the transplant are called minus days (Day -2,
Day -1, etc.). The day of the transplant is called Day 0. The days after the transplant are
called plus days (Day +1, Day +2, etc.).
On Day -8, you will be admitted to the hospital and you will begin receiving fluids by vein
to hydrate you. The fluids will be given as continuous (non-stop) infusion until you leave
the hospital.
On Days -8 through -2, you will take lenalidomide by mouth 1 time a day. The capsules should
be taken at around the same time every day with a cup (8 oz. ) of water. Do not break, chew,
or open the lenalidomide capsules. If you miss a dose of lenalidomide, you should not try
to make up the dose later. You should wait until the next scheduled dosing time to take
lenalidomide.
On Days -7 through -4, you will receive fludarabine by vein over about 1 hour.
On Day -4, you will receive melphalan by vein over about 30 minutes.
On Day -2, you will receive the NK cells by vein over about 30 minutes (first 3 patients
will not receive the NK cells).
On Day -1, you will not receive any study drugs or NK cells.
On Day 0, you will receive the UCB transplant.
Supportive Drugs:
You will be given drugs to help prevent side effects. The study staff will tell you about
these drugs, how they will be given, and the possible risks.
Starting on Day 0, you will begin receiving filgrastim (G-CSF) through a needle under the
skin 1 time every day until your white blood count begins to recover. Filgrastim is designed
to make white blood cells grow. This may help to fight infections.
Starting on Day -2, you will begin receiving tacrolimus by vein as a non-stop infusion until
you are able to take it by mouth. You will then take tacrolimus by mouth 2 times a day for
about 6 months. After that, your tacrolimus dose may be reduced if you do not have GVHD.
Your doctor will discuss this with you.
Starting on Day -3, you will begin taking mycophenolate mofetil (MMF) by mouth 2 times a day
with food. If you are not able to take the tablet by mouth, you will receive MMF by vein
over 2 hours, 2 times a day. If you do not have GVHD at Day 100, the dose of MMF will be
reduced. If you miss a dose of MMF you should tell your study doctor. You should not try to
make up the dose later.
Study Tests:
You will stay in the hospital for about 2-4 weeks after the UCB transplant. While you are in
the hospital, you will be checked for any side effects you may have and blood (about 2
teaspoons) will be drawn for routine tests whenever the doctor feels it is necessary.
After you are released from the hospital, you must remain in the Houston area to be
monitored for infections and other transplant-related side effects until about Day 100.
During this time, you will return to the clinic 1 time each week and the following tests and
procedures will be performed:
- You will be asked about how you are feeling and about any side effects you may be
having.
- Blood (about 2 teaspoons) will be drawn for routine tests.
About 6 weeks after the transplant (around Day 42), the following tests and procedures will
be performed:
- You will have a physical exam.
- You will be asked about how you are feeling and about any side effects you may be
having.
- Blood (about 4 teaspoons) will be drawn for routine tests and to check for side
effects, including GVHD.
At about 3, 6, and 12 months after the UCB transplant, the following tests and procedures
will be performed:
- You will have a physical exam.
- Blood (about 4 teaspoons) and urine will be drawn for routine tests and to check for
side effects, including GVHD. The blood will also be used to check how the UCB is being
"received" by your body.
- You will be asked about how you are feeling and about any side effects you may be
having.
- You may have a bone marrow biopsy to check the status of the disease if the doctor
thinks it is necessary. To collect a bone marrow biopsy, an area of the hip or other
site is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn
through a large needle.
Length of Study:
Your participation on this study will be over after you have completed the 12-month study
visit.
You will be taken off study if the disease gets worse, if intolerable side effects occur, if
your doctor thinks it is in your best interest, or if you are unable to follow the study
directions. You will also be taken off study if you are unable to receive the UCB
transplant, if you need medical treatment that is not allowed in this study, or if you have
any infections.
You must talk to the study doctor if you want to leave the study early. It may be
life-threatening to leave the study after you have started receiving study drugs but before
you have had the UCB transplant.
This is an investigational study. Fludarabine, melphalan, lenalidomide, and the UCB
transplant procedure are all FDA approved and commercially available for the treatment of
CLL. Fludarabine is approved for treatment of refractory CLL. Melphalan is approved for
the treatment of multiple myeloma (MM) but has been used in transplant conditioning
regimens. Lenalidomide is approved for the treatment of low risk myelodysplastic syndromes
and for MM.
The use of NK cells in patients with CLL is investigational.
Up to 13 participants will be enrolled in this study. All will be enrolled at MD Anderson.
Inclusion Criteria:
1. Patients with progressive CLL following standard therapy who meet European Bone
Marrow Transplant (EBMT) consensus guidelines of indications for allogeneic stem cell
transplantation. This includes patients with (1) lack of response or early relapse
within 1 year of receiving a purine analog-containing treatment regimen, (2) disease
relapse within 2 years of receiving a purine analog combination therapy or after
other therapies such as autologous stem cell transplantation, and (3) CLL associated
with p53 mutations or deletions and/or del(17p) requiring therapy. Patients must have
chemosensitive disease with at least a PR or SD with last treatment regimen.
2. Age less than 60 years of age.
3. Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.
4. Adequate major organ system function as demonstrated by: a. Left ventricular ejection
fraction greater than 45%. b. Pulmonary function test (PFT) demonstrating a diffusion
capacity of least 45% predicted. c. Creatinine < 1.6 mg/dL. d. SGPT/bilirubin 2.0 x normal.
5. Patients must be informed of the RevAssist® program and mandatory registration as
well as be willing and able to comply with its requirements.
6. Negative Beta HCG test in a woman with child bearing potential defined as not
post-menopausal for 12 months or no previous surgical sterilization and willing to
ongoing pregnancy testing while on treatment with lenalidomide.
7. Woman with child bearing potential must either commit to continued abstinence from
heterosexual intercourse or begin TWO acceptable methods of birth control, one highly
effective method and one additional effective method AT THE SAME TIME, at least 4
weeks before she starts taking lenalidomide.
8. Men must agree to use a latex condom during sexual contact with females of child
bearing potential even if they have had a successful vasectomy.
9. Patients must have two CB units available which are matched with the patient at 4, 5,
or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain
at least 1.5 x 107 total nucleated cells/Kg recipient body weight (pre-thaw). Cord
blood units will be procured through the NMDP (National Marrow Donor Program).
10. Have identified a back up cells source in case of engraftment failure. The source can
be autologous, related or unrelated.
11. Patients who have had a prior autologous transplant are eligible.
Exclusion Criteria:
1. Patients with known history of HIV/AIDS.
2. Active CNS disease in patient with history of CNS malignancy.
3. Patients with chronic active hepatitis or cirrhosis. If positive hepatitis serology,
the Study Chair may deem the patient eligible based on the results of liver biopsy.
4. Patients with known hypersensitivity to lenalidomide.
5. Patients who have a matched related donor who is eligible and willing to donate stem
cells.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Success Rate
Outcome Description:
Success is ability to generate adequate NK cells in a patient (a minimum of 3x10e8 natural killer (NK) cells). Success Rate is number of participants achieving success divided by total participants.
Outcome Time Frame:
3 months
Safety Issue:
No
Principal Investigator
Chitra M. Hosing, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2011-0493
NCT ID:
NCT01619761
Start Date:
May 2013
Completion Date:
Related Keywords:
- Leukemia
- Chronic Lymphocytic Leukemia
- Leukemia
- Chronic Lymphocytic Leukemia
- CLL
- Cord blood
- CB
- Umbilical cord blood
- UCB
- Natural killer cells
- NK
- Graft versus host disease
- GVHD
- Lenalidomide
- CC-5013
- Revlimid
- Fludarabine
- Fludarabine Phosphate
- Fludara
- Melphalan
- Alkeran
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
