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T-Cell or Natural Killer (NK) Cell Adback in Patients With Lymphoid Malignancies Receiving Allogeneic Stem Cell Transplantation With Campath-IH Containing Conditioning Regimens


Phase 2
N/A
70 Years
Not Enrolling
Both
Lymphoma, Leukemia

Thank you

Trial Information

T-Cell or Natural Killer (NK) Cell Adback in Patients With Lymphoid Malignancies Receiving Allogeneic Stem Cell Transplantation With Campath-IH Containing Conditioning Regimens


NK Cells, T-Cells, and the Study Drugs:

NK and T-cells from a donor may decrease the risk of relapse (reappearance of disease) after
stem cell transplantation. NK cells and T-cells are kinds of white blood cells. Both types
of cells have the ability to fight infection and "kill" tumor cells in the body. NK cells
are called "natural killers" because, unlike T-cells, NK cells do not need to be activated
("turned on") by an antigen (a foreign substance) in order to "attack" and "kill" tumor
cells.

Screening Tests:

Before starting treatment on this study, "screening tests" will be performed to help the
doctor determine eligibility to take part in this study.

- Physical exam.

- Blood drawn (about 6 1/2 to 8 tablespoons) for routine tests, to check the effects of
the transplantation, and for a liver function test. This routine blood draw will also
include a pregnancy test for women who are able to have children. To be eligible to
take part in this study, the pregnancy test must be negative.

- Urine collected for routine tests.

- Bone marrow biopsy performed to check the status of the disease. 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amount of bone marrow and bone is withdrawn through a large needle.

- Chest x-ray, computed tomography (CT) scans, and an electrocardiogram (ECG -- a test
that measures the electrical activity of the heart).

Study Treatment:

Treatment will begin within 30 days after the screening visit. All of the study drugs will
be given through a central venous catheter (CVC) that will be left in place throughout
treatment. A CVC is a sterile flexible tube that will be placed into a large vein while you
are under local anesthesia. Your doctor will explain this procedure in more detail, and a
signed separate consent form for this procedure is required

Before starting the chemotherapy in this study, 21 or more days must have elapsed since the
last biological therapy, chemotherapy, radiotherapy, or other investigational therapy.

PATIENTS RECEIVING BEAM, CAMPATH-IH, AND RITUXIMAB AS CONDITIONING:

BEAM is designed to kill leukemia and lymphoma cells by inserting itself into the cell DNA
(genetic material of cells).

Alemtuzumab is designed to attach to a foreign substance (antigen) that is found on certain
immune cells, which may cause the cells to die.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

On Day 1, BCNU will be given over 1 hour.

On Days 2-5, Ara-C will be given over 1 hour and etoposide over 3 hours. This will be
repeated every 12 hours during these 4 days.

On Days 2-4, alemtuzumab will be given over 30 minutes. Hydrocortisone and tacrolimus will
be given by vein during this time to help prevent or ease side effects, such as chills, skin
rash, and/or hives.

On Day 6, melphalan will be given over 30 minutes.

Rituximab will also be given over 5-7 hours, 13 days before the transplantation and then
once a week for a total of 4 doses.

On Day 7, after completion of chemotherapy, the blood or marrow stem cells that were
collected earlier will be transplanted (given to your body) through the CVC over 30-45
minutes. This is the standard treatment.

On Days +1, +3, and +6 after the stem cell infusion, methotrexate will be given by vein to
help decrease the risk of graft-versus-host disease.

G-CSF (filgrastim) will be injected just under your skin once a day until the neutrophil (a
type of white blood cell) counts recover.

About 60 patients will take part in this study. All will be enrolled at M. D. Anderson.

FOR PATIENTS RECEIVING FLUDARABINE, CYCLOPHOSPHAMIDE, CAMPATH-IH, RITUXIMAB,AND TBI:

TBI is designed to damage the DNA (the genetic material of cells) of cancer cells, which may
kill the cancer cells.

Alemtuzumab is designed to attach to a foreign substance (antigen) that is found on certain
immune cells, which may cause the cells to die.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may
slow or stop their growth and spread throughout the body. This may cause the cancer cells
to die.

Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic
material of cells). This may increase the likelihood of the cells dying.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

On Days 1-3, alemtuzumab will be given over 30 minutes, fludarabine over 1 hour, and
cyclophosphamide over 1 hour. Hydrocortisone and tacrolimus will be given by vein during
this time to help prevent or ease side effects, such as chills, skin rash, and/or hives.

Rituximab will also be given over 5-7 hours, 13 days before the transplantation and then
once a week for a total of 4 doses.

On Day 5, after completion of chemotherapy, TBI will be given, and later on the same day,
the blood stem cells that were collected earlier will be transplanted (given back to your
body) through the CVC over 30-45 minutes. This is the standard treatment.

On Days +1, +3, and +6 after the stem cell infusion, methotrexate will be given by vein to
help decrease the risk of graft-versus-host disease.

G-CSF (filgrastim) will be injected just under your skin once a day until the neutrophil (a
type of white blood cell) counts recover.

About 80 patients will take part in this study. All will be enrolled at M. D. Anderson.

ALL PATIENTS:

Infusion of NK Cells and T-Cells:

A "boost" of NK cells or T-cells from a donor may be given after blood stem cell
transplantation, depending on the disease status and the amount of donor cells in the blood.

If a complete remission (disappearance of cancer symptoms) is achieved at 3 months after
transplantation with more than 80% donor T-cells, no additional T-cells will be given.

If donor T-cells are less than 80% in the blood, then a boost of NK cells or T-cells will be
given. The type of cells given will depend on results of DNA testing that was done during
the screening visit to check the presence of molecules that may be able to activate ("turn
on") NK cells in a specific area of your DNA. The same type of cell infusion may be repeated
8 weeks later, if the percentage of donor T-cells does not reach 100% in the blood.

If active disease persists at 3 months after transplantation, 1 dose of rituximab will be
given once a week, or NK cells or T-cells will be given between the second and third dose of
rituximab. Infusion of NK cells or T-cells may be repeated every 6 weeks (up to 12 weeks),
if the disease does not achieve complete remission with the first infusion of cells.

It will be required to stay in the hospital from about 2 weeks before the transplantation
until about 2-3 weeks after the transplantation. The additional cells will be infused on an
outpatient basis.

Epinephrine and antihistamines will be available at the bedside during the NK cell infusion
to help treat any allergic reactions.

Study Visits:

It will be required to stay in the Houston area for about 100 days after the
transplantation. During initial study visits, the following tests/procedures will be
performed after the transplantation.

- Blood transfusions of blood and platelets as needed.

- Blood drawn (about 6 teaspoons) for routine tests.

- Blood drawn (about 6-10 tablespoons) to check the effects of the transplantation.

- Urine collected for routine tests.

- Imaging scans, such as the ones performed during the screening visit.

- Bone marrow biopsy performed, when it is necessary.

Between Days 25-35 after transplantation, and then at 3 months, CT scans, positron emission
tomography (PET), routine blood draws (about 6 teaspoons), and a bone marrow biopsy/aspirate
will be performed. These tests will be done to check the status of the disease.

Length of Study:

Length of time on this study up to about 3 years, unless the disease gets worse or any
intolerable side effects are experienced.

Follow-up:

After Day 35, if the disease is in remission with 100% donor cells, an evaluation will be
performed every 3 months during the first year and then every 6 months up to 3 years.

If the disease is not in remission by Days 90-100, CT scans, PET scans, routine blood tests
(about 6 teaspoons), and a bone marrow biopsy/aspirate will be performed every 6-8 weeks
(after each NK or T-cell infusion until remission is achieved ). Then, these tests will be
repeated every 6 months.

This is an investigational study. All of the drugs used in this study are FDA approved and
commercially available. The use of NK cells is not FDA approved and commercially available.
The use of the drugs and NK cells together in this study is investigational.


Inclusion Criteria:



1. Up to 70 years of age.

2. B-cell lymphoid malignancies (those with CD20 negative disease at their diagnosis
will not receive rituximab): This includes CLL/small lymphocytic lymphoma, follicular
lymphoma, mantle cell, diffuse large cell, Splenic lymphoma, Mucosa-Associated
Lymphoid Tissue (MALT), lymphoplasmacytic lymphoma and Burkitt's lymphoma.

3. Patients in relapse or considered at high risk for relapse.

4. In order to increase the chance of KIR-mismatching between recipient and donor, a
9/10 matched (mismatched locus C ) unrelated donor would be preferable. If a
mismatched donor is not available, then a fully-matched unrelated donor or other 9/10
matched unrelated donor will be considered.

5. A sibling donor who is 9/10 matched may also be allowed.

6. Zubrod PS
7. Left ventricular ejection fraction (LVEF)>/= 40% with no uncontrolled arrythmias or
symptomatic heart disease.

8. Forced expiratory volume in one second (FEV1), Forced Expiratory Volume (FVC) and
Carbon Monoxide Diffusing Capacity (DLCO) >/= 50%.

9. Serum creatinine < 1.8 mg/dL. Serum bilirubin < 3 * upper limit of normal,

10. Aspartate aminotransferase (AST) < 3 * upper limit of normal.

11. Signed, written Internal Review Board (IRB)-approved informed consent.

12. Men and women of reproductive potential must agree to follow accepted birth control
methods for the duration of the study. Female subject is either post-menopausal or
surgically sterilized or willing to use an acceptable method of birth control (i.e.,
a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom
with spermicide, or abstinence) for the duration of the study. Male subject agrees to
use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

1. Past history of anaphylaxis following exposure to CAMPATH-IH or Rituximab

2. Patient with active Central Nervous System (CNS) disease.

3. Positive Beta human chorionic gonadotrophin (hCG) text in a woman with child bearing
potential defined as not post-menopausal for 12 months or no previous surgical
sterilization, or currently breast-feeding.

4. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.

5. Patients with other malignancies diagnosed within 2 years prior to Study registration
(except skin squamous cell carcinoma).

6. Active uncontrolled bacterial, viral or fungal infections.

7. Major surgical procedure or significant traumatic injury within 4 weeks prior to
Study registration.

8. Serious, non-healing wound, ulcer, or bone fracture.

9. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Study registration.

10. History of Stroke within 6 months.

11. Myocardial infarction within the past 6 months prior to Study registration.

12. Uncontrolled chronic diarrhea.

13. A prior allogeneic transplant from the same donor. Is there an age limit? Yes

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

6-month Treatment Related Mortality (TRM)

Outcome Description:

Number of participant deaths in 6 months of T- cell or Natural killer (NK) cell adback treatment.

Outcome Time Frame:

6 Months

Safety Issue:

Yes

Principal Investigator

Issa F. Khouri, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2006-0230

NCT ID:

NCT00536978

Start Date:

September 2007

Completion Date:

November 2010

Related Keywords:

  • Lymphoma
  • Leukemia
  • Lymphoma
  • Leukemia
  • B-Cell Lymphoid Malignancies
  • CLL
  • Cll/Small Lymphocytic Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Diffuse Large Cell Lymphoma
  • Splenic Lymphoma
  • MALT
  • Lymphoplasmacytic Lymphoma
  • Burkitt's Lymphoma
  • ARA-C
  • BCNU
  • Campath-1H
  • Cytoxan
  • Etoposide
  • Fludarabine
  • Melphalan
  • Rituximab
  • Allogeneic Stem Cell Transplant
  • T-Cell Cell Adback
  • Natural Killer (NK) Cell Adback
  • Neoplasms
  • Leukemia
  • Lymphoma

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030