Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Active 70 and under Other 2005-0508 NCT00402558

Trial Description

Summary

The primary objectives are the following:

• To assess the safety of infusing alloreactive NK cells from a haploidentical relative and to determine the maximum tolerated dose of these cells given in combination with busulfan, fludarabine, Thymoglobulin and allogeneic transplantation from a separate HLA identical donor for treatment of AML/MDS.

• To determine if infusion of alloreactive haploidentical NK cells with busulfan and fludarabine/ATG will improve progression free survival post allogeneic stem cell transplantation from an HLA compatible donor compared to historical controls.

• To determine if infusion of alloreactive haploidentical NK cells effects the rate of engraftment, graft-vs-host disease (GVHD), immune reconstitution and survival.

Further Study Information

Patients:

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.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have routine blood tests (about 4 tablespoons) and urine tests performed, and a bone marrow biopsy will also be performed. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. You will have a chest x-ray, an electrocardiogram (ECG--a test to measure the electrical activity of the heart), and either a Multi-gated Acquisition (MUGA) scan or an echocardiogram (ECHO) to test the function of your heart. A MUGA scan uses a liquid that is injected into your vein that travels through your heart during the scan, while an ECHO uses sound waves to check heart function. You will have a lung function test performed. Women who are able to have children must have a negative blood pregnancy test before starting treatment.

If you are still 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. Some patients will receive interleukin-2 daily for 4 days.

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. Up to 48 patients will take part in this study.

NK Cell Donors:

NK cells are part of the immune system (the cells in the body that fight disease and infection). Sometimes, NK cells react against leukemia cells, particularly when they are mismatched for certain HLA tissue type proteins. When the NK cells react, these cells are called "alloreactive NK cells." Researchers would like to use your blood to collect NK cells to give your relative before their stem cell transplant.

If you agree to take part in this study, your blood will first be tested for any possible diseases (mainly viral infections) that could possibly be passed on to your relative. This test is required by health regulations. You will be told the results of this test. If you have one of these infections, you will not be able to participate in this study and may not be allowed to make routine blood donations.

If you are still allowed to take part in this study, your blood will be collected by a method called "apheresis," over 1-2 days. The blood will be drawn from a vein in your arm and will pass through a tube into a machine. This machine will pull out the white blood cells, the ones used to fight infections, and will leave the rest. These other blood cells will be given back to you through a tube and needle inserted in your other arm.

During this procedure, you will be given a dose of ACD-A, a chemical that will keep your blood from clotting in the tubes. During the procedure, the level of calcium in your blood may fall to a low level. You will be given a liquid through a needle in your vein that has calcium, to help replace some of this.

The apheresis process takes about 4-6 hours. If enough white blood cells cannot be collected in the first apheresis procedure, a second procedure will be done. The white blood cells that are collected will be processed in the laboratory. There, researchers will use a machine to separate the NK cells and make them stronger, before they will be given to your relative. Your participation in this study is done after the apheresis.

Researchers will throw away any NK cells that are left over after the stem cell infusion and any needed testing are done.

This is an investigational study. The method of making and transplanting the alloreactive NK cells is investigational. Up to 48 donors will take part in this study. All will be enrolled at M. D. Anderson.

Eligibility Criteria

Inclusion:

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 related or unrelated donor willing to donate for allogeneic peripheral blood progenitor cell transplantation.

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. FEV1, FVC and DLCO >/= 50% of expected, corrected for hemoglobin.

7. Serum creatinine </= 1.8mg%.

8. 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:

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 21 days prior to trial enrollment. (Hydroxyurea or low dose ara-c < 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 has been in remission for at least 3 months prior to enrollment on this study).

Trial Contact Information

Trial Lead Organizations/Sponsors

M. D. Anderson Cancer Center at University of Texas

Richard E. Champlin, MD

Principal Investigator

Richard E. Champlin, MD

Ph: 713-792-8750

U.S.A.
Texas
	Houston
	M. D. Anderson Cancer Center at University of Texas
		Richard E. Champlin, MD	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00402558
Information obtained from ClinicalTrials.gov on August 04, 2008