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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


Phase 1/Phase 2
18 Years
75 Years
Open (Enrolling)
Both
Myeloma

Thank you

Trial Information

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.

Study Visits

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
needle.

- 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
disease.

- 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.

Long-Term Follow-Up:

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.


Inclusion Criteria:



1. Patients with multiple myeloma who are transplant candidates.

2. 18 to 75 years of age.

3. Performance score of at least 70% by Karnofsky or 0 to 2 ECOG.

4. Adequate major organ system function as demonstrated by: a. Left ventricular ejection
fraction greater than 40%. b. Pulmonary function test (PFT) demonstrating a diffusion
capacity of least 40% predicted. c. Estimated serum creatinine clearance >/=60 ml/min
(using the Cockcroft-Gault formula: creatinine clearance = [(140-age)*kg/(72*serum
creatinine)] * 0.85 if female) and/or serum creatinine than 3 x upper limit of normal. e. Total bilirubin less than 2 x upper limit of
normal.

5. Patients must be informed of the RevAssist® program and mandatory registration and be
willing and able to comply with its requirements.

6. Females of childbearing potential (FCBP) must have a negative serum pregnancy test
with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again 24
hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and
must either commit to continued abstinence from heterosexual intercourse or begin TWO
acceptable methods or birth control, one highly effective method and one additional
effective method AT THE SAME TIME, at least 28 days before she starts taking
lenalidomide. FCBP must also agree to ongoing pregnancy testing.

7. 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.

8. Patients must have a CB unit available which is matched with the patient at 4, 5, or
6/6 HLA class I (serological) and II (molecular) antigens.

9. Availability of autologous peripheral blood stem cell graft, containing at least 6.0
x 10^6 CD34+ cells/kg.

10. Patient or legally authorized representative able to sign informed consent.

Exclusion Criteria:

1. Patients receiving any other investigational agents.

2. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to melphalan.

3. Known hypersensitivity or desquamating rash to either thalidomide or lenalidomide.

4. Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, uncontrolled hypertension (systolic >140, diastolic >90 despite
antihypertensive therapy, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.

5. HIV-positive patients are excluded due to increased risk of lethal infections when
treated with myeloablative chemotherapy.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD) of umbilical cord blood (UCB)-derived natural killer (NK) cells

Outcome Description:

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.

Outcome Time Frame:

30 Days

Safety Issue:

Yes

Principal Investigator

Nina Shah, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2011-0379

NCT ID:

NCT01729091

Start Date:

June 2013

Completion Date:

Related Keywords:

  • Myeloma
  • Myeloma
  • Multiple myeloma
  • MM
  • Umbilical cord blood
  • UCB
  • Natural killer cells
  • NK
  • Autologous stem cell transplant
  • Stem cell infusion
  • High dose chemotherapy
  • Lenalidomide
  • CC-5013
  • Revlimid
  • Melphalan
  • Alkeran
  • Interleukin-2
  • IL-2
  • Aldesleukin
  • Proleukin
  • G-CSF
  • Filgrastim
  • Neupogen
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030