NK Cells to Prevent Disease Relapse for Patients High Risk Myeloid Malignancies
| Status: | Recruiting |
|---|---|
| Conditions: | Blood Cancer, Hematology, Leukemia |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | 2 - 65 |
| Updated: | 2/21/2019 |
| Start Date: | April 22, 2014 |
| End Date: | April 2020 |
| Contact: | Stefan Ciurea, MD |
| Phone: | 713-792-8750 |
A Phase I/II Clinical Trial of Natural Killer (NK) Cells Administration to Prevent Disease Relapse for Patient With High-Risk Myeloid Malignancies Undergoing Haploidentical Stem-Cell Transplantation
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential
participant.
The goal of this clinical research study is to learn about the safety of giving a kind of
immune cells called "natural killer" (NK) cells with standard chemotherapy and an allogeneic
stem cell transplant (using cells from a donor). Researchers also want to learn the highest
tolerable dose of NK cells that can be given.
Immune system cells (such as NK cells) are made by the body to attack foreign or cancerous
cells. Researchers believe that the NK cells you receive from the donor may react against the
leukemia cells in your body, help eliminate leukemia, and prevent disease relapse.
This is an investigational study. The study drugs are FDA approved and commercially available
for the treatment of blood cancers and/or stem cell transplant. The way the researchers
process the NK cells and the infusion of them is investigational and is not FDA approved.
Up to 45 participants will be enrolled in this study. All will take part at MD Anderson.
participant.
The goal of this clinical research study is to learn about the safety of giving a kind of
immune cells called "natural killer" (NK) cells with standard chemotherapy and an allogeneic
stem cell transplant (using cells from a donor). Researchers also want to learn the highest
tolerable dose of NK cells that can be given.
Immune system cells (such as NK cells) are made by the body to attack foreign or cancerous
cells. Researchers believe that the NK cells you receive from the donor may react against the
leukemia cells in your body, help eliminate leukemia, and prevent disease relapse.
This is an investigational study. The study drugs are FDA approved and commercially available
for the treatment of blood cancers and/or stem cell transplant. The way the researchers
process the NK cells and the infusion of them is investigational and is not FDA approved.
Up to 45 participants will be enrolled in this study. All will take part at MD Anderson.
Dose Levels:
If you agree to take part in this study, you will be assigned to a dose level of NK cells
based on when you joined this study. 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 for up to 6 dose levels, until the
highest tolerable dose of NK cells is found.
The day you receive the stem cell transplant is called Day 0. The days before you receive
your stem cell transplant are named with a minus sign (-). The days after you receive the
stem cell transplant are named with a plus sign (+).
You will receive 1 of 2 chemotherapy treatments that will be chosen by your doctor. The
treatment will be selected based on your age and health. The types include a high-dose
regimen and a reduced-intensity regimen.
Study Drug Administration (High Dose Regimen):
On Day -8, you will be admitted to the hospital and given fluids by vein.
On Day -7, you will receive melphalan by vein over 30 minutes.
On Days -7 through -4, you will receive fludarabine by vein over 1 hour. Fludarabine and
melphalan are 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 -3, you will receive total body irradiation (TBI). TBI involves the delivery of high
doses of radiation designed to destroy cancer cells and/or lower the immune system in order
to lower the risk of the body rejecting the new stem cells.
On Day -2 or Day -1, you will receive NK cells by vein over 30 minutes.
On Day -1, you will "rest" (not receive chemotherapy).
On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere
from about 30 minutes to several hours.
On Days +3 and +4, you will receive 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 donor NK and stem cells, attacks the
tissues of the recipient's body). You will also receive mesna by vein over 30 minutes every 4
hours for a total of 10 mesna doses on Days +3 and +4. Mesna is given to lower the risk of
side effects to the bladder caused by cyclophosphamide.
Starting on Day +5, you will receive tacrolimus and mycophenolate mofetil (MMF) to help lower
the risk of GVHD. Tacrolimus will be given by vein non-stop for about 2 weeks. After the 2
weeks of taking tacrolimus by vein, you will take tacrolimus by mouth as a pill for at least
4 months after the transplant. MMF will be given by mouth, 3 times a day, usually for about
6-7 months.
Starting on Day +7, you will receive filgrastim-sndz as an injection under the skin 1 time a
day, until your blood cell levels are high enough. Filgrastim-sndz is designed to help with
the growth of a type of healthy white blood cells that fight infection.
On Day +7 (+/- 1 day) and once about 3-12 weeks later, you will receive NK cells by vein over
30 minutes.
You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.
Study Drug Administration (Reduced Intensity Regimen) If your study doctor thinks it is
needed due to illness or your age, you will receive a reduced intensity regimen.
On Day -9, you will be admitted to the hospital and given fluids by vein.
On Day -8, you will receive melphalan by vein over 30 minutes.
On Days -7 through -4, you will receive fludarabine by vein over 1 hour.
On Day -3, you will receive total body irradiation (TBI). TBI involves the delivery of high
doses of radiation designed to destroy cancer cells and/or lower the immune system in order
to lower the risk of the body rejecting the new stem cells.
On Day -2 or Day -1, you will receive NK cells by vein over 30 minutes.
On Day -1, you will "rest" (not receive chemotherapy).
On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere
from about 30 minutes to several hours.
On Days +3 and +4, you will receive cyclophosphamide by vein over 3 hours. You will also
receive mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses on Days +3
and +4. Mesna is given to lower the risk of side effects to the bladder.
Starting on Day +5, you will receive tacrolimus and MMF to help lower the risk of GVHD.
Tacrolimus will be given by vein non-stop for about 2 weeks. After the 2 weeks of taking
tacrolimus by vein, you will take tacrolimus by mouth as a pill for at least 4 months after
the transplant. MMF will be given by mouth, 3 times a day, usually for about 6-7 months.
Starting on Day +7, you will receive filgrastim-sndz as an injection under the skin 1 time a
day, until your blood cell levels are high enough. Filgrastim-sndz is designed to help with
the growth of white blood cells.
On Day +7 (+/- 1 day) and once about 3-12 weeks later, you will receive NK cells by vein over
30 minutes.
You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.
Study Testing:
Before you are sent home from the hospital and/or clinic, you will receive additional written
instructions. These instructions will include how often you will come to the hospital/clinic,
which standard drugs you will take at home, and what side effects you may have and what to do
for them.
After finishing the chemotherapy and cell infusion, your follow-up care will be routine
standard of care follow-up that all patients receiving allogeneic stem cell transplantation
receive. At each visit, you will have a physical exam. You will be asked about any side
effects you may have had. Blood (about 1 tablespoon) will be drawn for routine tests. If the
doctor thinks it is needed, you will have a bone marrow aspiration to check the status of the
disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed with
anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
Blood (up to about 4 tablespoons) will be drawn to test the genetic makeup and function of
the infused NK cells and to check the status of the disease about once a week for the first 4
weeks after the transplant, before the 3rd NK cell infusion and about 1 week later, and then
about 3, 6, and 12 months after the transplant, if possible. This may be repeated, if your
doctor thinks it is needed.
Length of Treatment:
Your active participation in this study will be over 12 months after the transplant. You will
be off study 2 years after the transplant. Between Years 1 and 2 after the transplant, the
study staff may check your medical record to see how you are doing. You may be taken off
study early if the doctor thinks it is in your best interest, if the disease gets worse or
comes back requiring further treatment, if intolerable side effects occur, if not enough NK
cells can be collected, or if you are unable to follow study directions.
If for any reason you want to leave the study early, you must talk to the study doctor. It
may be life-threatening to leave the study after you have started to receive the study drugs
but before you receive the stem cell transplant because your blood cell counts will be
dangerously low.
If you agree to take part in this study, you will be assigned to a dose level of NK cells
based on when you joined this study. 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 for up to 6 dose levels, until the
highest tolerable dose of NK cells is found.
The day you receive the stem cell transplant is called Day 0. The days before you receive
your stem cell transplant are named with a minus sign (-). The days after you receive the
stem cell transplant are named with a plus sign (+).
You will receive 1 of 2 chemotherapy treatments that will be chosen by your doctor. The
treatment will be selected based on your age and health. The types include a high-dose
regimen and a reduced-intensity regimen.
Study Drug Administration (High Dose Regimen):
On Day -8, you will be admitted to the hospital and given fluids by vein.
On Day -7, you will receive melphalan by vein over 30 minutes.
On Days -7 through -4, you will receive fludarabine by vein over 1 hour. Fludarabine and
melphalan are 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 -3, you will receive total body irradiation (TBI). TBI involves the delivery of high
doses of radiation designed to destroy cancer cells and/or lower the immune system in order
to lower the risk of the body rejecting the new stem cells.
On Day -2 or Day -1, you will receive NK cells by vein over 30 minutes.
On Day -1, you will "rest" (not receive chemotherapy).
On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere
from about 30 minutes to several hours.
On Days +3 and +4, you will receive 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 donor NK and stem cells, attacks the
tissues of the recipient's body). You will also receive mesna by vein over 30 minutes every 4
hours for a total of 10 mesna doses on Days +3 and +4. Mesna is given to lower the risk of
side effects to the bladder caused by cyclophosphamide.
Starting on Day +5, you will receive tacrolimus and mycophenolate mofetil (MMF) to help lower
the risk of GVHD. Tacrolimus will be given by vein non-stop for about 2 weeks. After the 2
weeks of taking tacrolimus by vein, you will take tacrolimus by mouth as a pill for at least
4 months after the transplant. MMF will be given by mouth, 3 times a day, usually for about
6-7 months.
Starting on Day +7, you will receive filgrastim-sndz as an injection under the skin 1 time a
day, until your blood cell levels are high enough. Filgrastim-sndz is designed to help with
the growth of a type of healthy white blood cells that fight infection.
On Day +7 (+/- 1 day) and once about 3-12 weeks later, you will receive NK cells by vein over
30 minutes.
You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.
Study Drug Administration (Reduced Intensity Regimen) If your study doctor thinks it is
needed due to illness or your age, you will receive a reduced intensity regimen.
On Day -9, you will be admitted to the hospital and given fluids by vein.
On Day -8, you will receive melphalan by vein over 30 minutes.
On Days -7 through -4, you will receive fludarabine by vein over 1 hour.
On Day -3, you will receive total body irradiation (TBI). TBI involves the delivery of high
doses of radiation designed to destroy cancer cells and/or lower the immune system in order
to lower the risk of the body rejecting the new stem cells.
On Day -2 or Day -1, you will receive NK cells by vein over 30 minutes.
On Day -1, you will "rest" (not receive chemotherapy).
On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere
from about 30 minutes to several hours.
On Days +3 and +4, you will receive cyclophosphamide by vein over 3 hours. You will also
receive mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses on Days +3
and +4. Mesna is given to lower the risk of side effects to the bladder.
Starting on Day +5, you will receive tacrolimus and MMF to help lower the risk of GVHD.
Tacrolimus will be given by vein non-stop for about 2 weeks. After the 2 weeks of taking
tacrolimus by vein, you will take tacrolimus by mouth as a pill for at least 4 months after
the transplant. MMF will be given by mouth, 3 times a day, usually for about 6-7 months.
Starting on Day +7, you will receive filgrastim-sndz as an injection under the skin 1 time a
day, until your blood cell levels are high enough. Filgrastim-sndz is designed to help with
the growth of white blood cells.
On Day +7 (+/- 1 day) and once about 3-12 weeks later, you will receive NK cells by vein over
30 minutes.
You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.
Study Testing:
Before you are sent home from the hospital and/or clinic, you will receive additional written
instructions. These instructions will include how often you will come to the hospital/clinic,
which standard drugs you will take at home, and what side effects you may have and what to do
for them.
After finishing the chemotherapy and cell infusion, your follow-up care will be routine
standard of care follow-up that all patients receiving allogeneic stem cell transplantation
receive. At each visit, you will have a physical exam. You will be asked about any side
effects you may have had. Blood (about 1 tablespoon) will be drawn for routine tests. If the
doctor thinks it is needed, you will have a bone marrow aspiration to check the status of the
disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed with
anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
Blood (up to about 4 tablespoons) will be drawn to test the genetic makeup and function of
the infused NK cells and to check the status of the disease about once a week for the first 4
weeks after the transplant, before the 3rd NK cell infusion and about 1 week later, and then
about 3, 6, and 12 months after the transplant, if possible. This may be repeated, if your
doctor thinks it is needed.
Length of Treatment:
Your active participation in this study will be over 12 months after the transplant. You will
be off study 2 years after the transplant. Between Years 1 and 2 after the transplant, the
study staff may check your medical record to see how you are doing. You may be taken off
study early if the doctor thinks it is in your best interest, if the disease gets worse or
comes back requiring further treatment, if intolerable side effects occur, if not enough NK
cells can be collected, or if you are unable to follow study directions.
If for any reason you want to leave the study early, you must talk to the study doctor. It
may be life-threatening to leave the study after you have started to receive the study drugs
but before you receive the stem cell transplant because your blood cell counts will be
dangerously low.
Inclusion Criteria:
1. Patients age 18 to 65 years old. Eligibility for pediatric patients will be determined
in conjunction with an MDACC pediatrician. Patients age 2-17 years old may be enrolled
after at least 4 adults (ages 18-65 years old) have been treated without toxicity, as
defined in the Statistical Considerations section.
2. Patient with no matched related donor who has a related haploidentical donor
identified ( bone marrow harvest and an NK cell collection approximately 2 weeks of the recipient's
admission for transplant. The donor must be 16 years of age or older and weigh at
least 110 pounds.
3. Patients with one of the following diseases: Acute myeloid leukemia (AML): a. First
complete remission with high-risk features defined as: (i) Greater than 1 cycle of
induction therapy required to achieve remission; (ii) Preceding myelodysplastic
syndrome (MDS); (iii) Presence of FLT3 mutations or internal tandem duplication or
other mutations associated with poor-risk AML (e.g. DNMT3A, TET2); (iv) FAB M6 or M7
classification; (v) Adverse cytogenetics: -5, del 5q, -7, del7q, abnormalities
involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype [> 3 abnormalities]; (vi)
Treatment-related AML, or b. Second or greater remission; patients beyond second
remission have to be in CR at transplant to be eligible, or c. Primary induction
failure with partial response to therapy who achieve adequate cytoreduction.
4. Patients with myelodysplastic syndromes (MDS): a. De novo MDS with intermediate or
high-risk IPSS scores. Patients with intermediate-1 features should have failed to
respond to hypomethylating agent therapy, or b. Patients with treatment-related MDS.
5. Chronic myeloid leukemia (CML): a. Failed to achieve cytogenetic remission or have
cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or b.
Accelerated phase or blast phase at any time.
6. Performance score of at least 70% by Karnofsky or 0 to 1 by ECOG (age >/= 12 years),
or Lansky Play-Performance Scale of at least 70% or greater (age <12 years).
7. Adequate major organ system function as demonstrated by: Serum creatinine clearance
equal or more than 50 ml/min (calculated with Cockcroft-Gault formula).
8. Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease. ALT or AST equal
or less than 200 IU/ml for adults. Conjugated (direct) bilirubin less than 2x upper
limit of normal.
9. Left ventricular ejection fraction equal or greater than 40%.
10. Diffusing capacity for carbon monoxide (DLCO) equal or greater than 50% predicted
corrected for hemoglobin. For children PFT, oxygen saturation >/= 92% on room air by pulse oximetry.
11. Patient or patient's legal representative, parent(s) or guardian should provide
written informed consent. Assent of a minor if participant's age is at least seven and
less than eighteen years.
Exclusion Criteria:
1. HIV positive; active hepatitis B or C.
2. Uncontrolled infections; PI is the final arbiter of this criterion.
3. Liver cirrhosis.
4. CNS involvement within 3 months.
5. Positive pregnancy test in a woman with child bearing potential defined as not
post-menopausal for 12 months or no previous surgical sterilization.
6. Inability to comply with medical therapy or follow-up.
We found this trial at
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site
1515 Holcombe Blvd
Houston, Texas 77030
Houston, Texas 77030
713-792-2121
University of Texas M.D. Anderson Cancer Center The mission of The University of Texas MD...
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