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Alloreactive NK Cells With Busulfan, Fludarabine and Thymoglobulin for Allogeneic Stem Cell Transplantation for AML and MDS


Phase 1/Phase 2
N/A
70 Years
Open (Enrolling)
Both
Myelodysplastic Syndrome, Leukemia

Thank you

Trial Information

Alloreactive NK Cells With Busulfan, Fludarabine and Thymoglobulin for Allogeneic Stem Cell Transplantation for AML and MDS


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.


Inclusion Criteria:



1. Patients with age 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
5. Left ventricular ejection fraction >/= 45%. No uncontrolled arrhythmias or
uncontrolled symptomatic cardiac disease.

6. No symptomatic pulmonary disease. FEV1, FVC and DLCO >/= 50% of expected, corrected
for hemoglobin.

7. Serum creatinine
8. SGPT
9. Bilirubin 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 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 LMD, that is in remission prior to enrollment on this study).

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 of NK cells

Outcome Time Frame:

Continual Reassessment (Baseline, 3, 6 and 12 Months Follow Ups)

Safety Issue:

Yes

Principal Investigator

Richard E. Champlin, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2005-0508

NCT ID:

NCT00402558

Start Date:

May 2006

Completion Date:

Related Keywords:

  • Myelodysplastic Syndrome
  • Leukemia
  • Acute Myeloid Leukemia
  • Chronic Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • Leukemia
  • NK Cells
  • Natural Killer Cells
  • Fludarabine
  • Busulfan
  • Thymoglobulin
  • AML
  • CML
  • MDS
  • ATG
  • Antithymocyte globulin
  • Busulfex
  • Myleran®
  • Fludarabine Phosphate
  • G-CSF
  • Filgrastim
  • Neupogen
  • Interleukin-2
  • IL-2
  • Aldesleukin
  • Proleukin
  • Tacrolimus
  • Prograf
  • Methotrexate
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location
UT MD Anderson Cancer Center Houston, Texas  77030