Alloreactive NK Cells for Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Myelodysplastic Syndrome; Leukemia
Intervention: Thymoglobulin (Drug); Busulfan (Drug); Fludarabine (Drug); Alloreactive NK Infusion (Procedure); G-CSF (Drug); Tacrolimus (Drug); Methotrexate (Drug); Interleukin-2 (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: M.D. Anderson Cancer Center Official(s) and/or principal investigator(s): Richard E. Champlin, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center
Summary
The goal of this clinical research study is to determine the safety and effects of giving a
special kind of immune cells called "alloreactive natural killer (NK) cells" with high dose
chemotherapy and allogeneic hematopoeitic stem cell transplantation with the goal of
defining the maximum tolerated dose of NK cells. The NK cells will be donated from a
relative of yours who has certain genetic type in their blood called HLA, that almost
matches yours. The stem cells you will receive will come from a separate HLA matched (HLA
A, B, C, DR) relative or unrelated donor. The safety of this treatment will also be
studied.
Clinical Details
Official title: Alloreactive NK Cells With Busulfan, Fludarabine and Thymoglobulin for Allogeneic Stem Cell Transplantation for AML and MDS
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Maximum Tolerated Dose of NK cells
Detailed description:
NK cells are part of the immune system (the cells in your body that fight disease).
Sometimes, NK cells react against and fight leukemia cells that are mismatched with your
body for certain HLA tissue type proteins. When the NK cells react, these cells are called
"alloreactive NK cells."
In this study, researchers will collect alloreactive NK cells from the blood of a relative
of yours whose HLA proteins do not match yours exactly. The NK cells are separated from the
blood using a machine called a CLINIMACs system. This machine uses special kinds of cells
and magnetic beads to separate the NK cells. The drug interleukin-2 is then added to the NK
cells, to improve their function. The interleukin-2 will be washed out of the cell sample
before it is given to you. The CliniMACS System is a medical device that is used to
separate types of blood cells from blood that is removed from the body during leukapheresis.
These separated cells are processed for use in treatments such as stem cell transplants.
If you are able to take part in this study, you will receive high-dose chemotherapy for 4
days. You will receive fludarabine over about 30 minutes daily as an intravenous
(IV--through a needle in your vein) infusion . You will also receive busulfan over 3 hours
by IV once a day. About 2 days later, you will be given the infusion of the alloreactive NK
cells by IV. Patients will receive one of 3 dose levels. Some patients will receive
interleukin-2 daily for 4 days to enhance the function of the NK cells.
Five (5) days after the NK cell infusion, thymoglobulin will be given to you by IV daily for
3 days. Thymoglobulin is an immunosuppressive treatment to reduce the risk of graft
rejection. Then blood stem cells will be administered IV from a different stem cell donor
whose HLA type matches yours.
You will receive the drugs tacrolimus and methotrexate to help lower the risk of a reaction
called "graft-vs.-host disease" (GVHD). GVHD is when the donated immune cells in the
transplant react against the body of the person receiving the cells. Tacrolimus will be
given by IV for about 2 weeks, and after that it is given by mouth as a pill for at least 3
months. Methotrexate will be given as an IV injection for 3 to 4 doses over the first 11
days after the stem cell transplant.
You will also receive the drug G-CSF (Neupogen) as an injection under the skin until your
blood cell counts reach a certain high enough level.
You will need to stay in the hospital for about 4 weeks. After you leave the hospital, you
will continue as an outpatient in the hospital area, which means you will have to stay close
enough to be able to come back for any visits for at least 100 days after the transplant.
You will be asked to come back to the clinic at 3, 6, and 12 months after your transplant
for routine safety testing. This will include a physical exam, a bone marrow biopsy, and
routine blood draws.
This is an investigational study. The way the researchers make the alloreactive NK cells
using the CLINIMACs device is investigational. The CliniMACS device is not FDA approved.
At this time, it is being used in research only. Up to 18 patients will take part in this
study.
Eligibility
Minimum age: N/A.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Patients with age = 70 years with one of of the following: Acute myeloid leukemia
past first remission, in first or subsequent relapse, in second or greater remission
or primary induction failure; Myelodysplastic syndromes with intermediate or high
risk IPSS score; CML which has progressed to accelerated phase or blast crisis
despite imatinib treatment
2. Patients must have an HLA matched (HLA A, B, C, DR) related or unrelated donor
willing to donate for allogeneic peripheral blood progenitor cell transplantation.
(Recent large analyses of the National Marrow Donor Program indicate that a mis-match
at the DQ locus has no adverse effect on outcome. The current national standard of
care is to consider only these 4 loci in identifying suitably "matched" donors.)
3. Patients must have a haploidentical relative who is predicted to be alloreactive
based upon the presence of the relevant KIR genes and incompatibility with the
recipient for HLA C and Bw antigens.
4. Zubrod performance status = 2.
5. Left ventricular ejection fraction >/= 45%. No uncontrolled arrhythmias or
uncontrolled symptomatic cardiac disease.
6. No symptomatic pulmonary disease. forced expiratory volume at one second (FEV1),
forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO)
>/= 50% of expected, corrected for hemoglobin.
7. Serum creatinine = 1. 8mg%.
8. Serum glutamate pyruvate transaminase (SGPT) = 200 IU/ml unless related to patients
malignancy.
9. Bilirubin = 1. 5 mg/dl (unless Gilbert's syndrome).No evidence of chronic active
hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman
and consider liver biopsy.
10. Patient or patient's legal representative, parent(s) or guardian able to sign
informed consent.
11. No known allergy to mouse proteins or monoclonal antibodies
Exclusion Criteria:
1. Uncontrolled infection, not responding to appropriate antimicrobial agents after
seven days of therapy. The Protocol PI is the final arbiter of eligibility.
2. Pleural/pericardial effusion or ascites estimated to be >1L.
3. HIV-positive.
4. Pregnancy: Positive Beta Human Chorionic Gonadotropin (HCG) test in a woman with
child bearing potential defined as not post-menopausal for 12 months or no previous
surgical sterilization.
5. Known allergy to mouse proteins.
6. Patient has received other systemic chemotherapeutic drugs (including Mylotarg)
within 14 days prior to trial enrollment or has unresolved grade >1 toxicity from
prior chemotherapy treatment. (Hydroxyurea or low dose ara-c less than or equal to 20
mg/m2/d is permitted if indicated to control induction refractory disease, and IT
chemotherapy is allowed if indicated as maintenance treatment for previously
diagnosed lumbar microdiscectomy (LMD), that is in remission prior to enrollment on
this study).
Locations and Contacts
UT MD Anderson Cancer Center, Houston, Texas 77030, United States
Additional Information
University of Texas MD Anderson Cancer Center Website
Starting date: May 2006
Last updated: May 6, 2015
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