Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Interleukin-2

Mesna

Epratuzumab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Analgesics, Non-Narcotic

Antineoplastic Agents, Immunological

Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m\^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m\^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours. Mesna 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.

360 mg/m\^2 once a day by vein on Day -4, Day -1 and Days 3, 6, 10, 13 and 17.

25 mg/m\^2 once a day by vein on Day -6 through Day -2 over 30 minutes.

60 mg/kg once a day by vein on Days -5 and -4 over 2 hours.

12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.

Transplant of Haploidentical NK cells by vein on Day 0.

Infusion of NK cells

Subcutaneous injections three times a week for 9 doses on Days 0 to 21.

Anna Franklin, MD

The goal of this clinical research study is to learn if transferring the donor's NK cells, in combination with an antibody called epratuzumab and low-dose interleukin (IL-2), into your body can be done safely. Researchers want to find out if the infused NK cells will survive after the infusion and if the NK cell infusion helps to destroy cancer cells in the recipient's body and possibly to help control the disease.

Primary Objectives:

· Evaluate the feasibility of collecting an adequate number of natural killer (NK) cells from a donor and evaluate the safety of a haploidentical donor-derived NK cell infusion, Epratuzumab, and low-dose interleukin-2 (IL-2).

Secondary Objectives:

* Quantification and persistence of the infused donor NK cell in vivo;
* Quantification and persistence of cytokine levels;
* Assessment of NK cell immunophenotype and function;
* Correlate above with anti-tumor effect.

Study Drugs:

Epratuzumab is designed to attach to certain proteins on the surface of ALL cells. This may cause the cancer cells to die.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth. 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.

IL-2 is designed to help NK cells live longer and work better.

Experimental Therapy:

NK cells are the cells in the body that fight disease and infection. NK cells may destroy tumor cells, particularly when the NK cells are "mismatched" for certain proteins, called human leukocyte antigens (HLA). Researchers think that this ability to destroy tumor cells can be predicted by learning the donor's and the recipient's HLA types to see if they are a mismatch, and by checking for other specialized proteins found on the surface of the donor's NK cells. These proteins are called killer immunoglobulin receptors (KIR).

The NK cells will be collected from the donor's blood and then processed in a lab at M. D. Anderson, where researchers will use a machine, called a CliniMACS device, to separate out the NK cells from the rest of the donor's collected white blood cells and treat them overnight with a drug called IL-2. This is done to make the NK cells stronger before they are given to the recipient. You will also receive IL-2 injections under your skin to try to help the NK cells survive longer and to possibly increase the number of NK cells in your body after the infusion.

Screening Tests:

Before you can start treatment on this study, you will have "screening tests" to help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:

* You will have a bone marrow biopsy and/or aspiration to check the status of the disease. To collect a bone marrow biopsy and/or aspirate, an area of the hip is numbed with an anesthetic, and a small amount of bone marrow and bone is withdrawn through a needle.
* You will have a spinal tap to check the status of the disease. A spinal tap (also called a lumbar puncture) is when a special needle is inserted into the lower back through the space between the bones to draw a sample of the fluid that surrounds the spinal cord.
* You will have a pulse oximetry test to measure your heart rate and the level of oxygen in the blood. To perform this test, a clothespin-shaped device will be placed on your finger for about 1 minute.
* Your medical history will be recorded.
* You will have a physical exam, including a measurement of your vital signs (blood pressure, heart rate, breathing rate, and temperature).
* Blood (about 4 tablespoons) will be drawn for routine tests. This blood will also be checked for infections such as the human immunodeficiency virus (HIV). You will be told the results of this test. If you have an infection, you may not be able to take part in this study.
* Blood (about 2 tablespoons) will be drawn to test for HLA and KIR. You and the donor will be told the results of this test.
* Females who are able to have children must have a negative blood pregnancy test. This test will be performed with the blood drawn for routine tests as described above. If there is not enough blood leftover for this test, additional blood (about 1 teaspoon) will be drawn.

These screening tests, except for the HLA and KIR-typing, would also need to be repeated before an additional leukapheresis procedure can be done as a part of this study, in order to see if you continue to be eligible to have another one performed.

Identifying an Eligible Donor:

Your relative will be tested to see if his or her KIR has a type of "mismatch" that researchers think will help the donor's NK cells target the cancer cells in your body. They must also share half of your HLA genes to be eligible to take part in this study.

The donor's blood will also be checked for infections, such as HIV, to protect against the possibility of transmitting an infection to you during the NK cell infusion.

To help track the NK cells after infusion, researchers prefer (but do not require) that if you are a female recipient, your donor is male and if you are a male recipient, your donor is female.

Epratuzumab Administration:

If you and the donor are found to be eligible to take part in this study, on Day -4 (4 days before the NK cell infusion) and Day -1 (1 day before the NK cell infusion), you will have an epratuzumab infusion. The length of time this infusion will take will be different for each patient. This will be done using an indwelling catheter (a tube that remains in a vein, such as tunneled in the arm or through the chest to continuously inject or drain a part of your body). If you already have an indwelling catheter in place, you will not need to have a new one placed. However, if a new catheter is needed, you will be asked to sign a separate informed consent form for its placement.

On Day -1 (1 day before the NK cell infusion) and on Days 3, 6, 10, 13, and 17, you will receive an epratuzumab infusion. This will take several hours.

Conditioning Phase:

This phase will start within 28 days after the screening tests. During this phase, you will receive chemotherapy with cyclophosphamide and fludarabine to weaken your immune system in order to help the infused NK cells survive. You will stay in the hospital from Day -6 until after the NK cell infusion or longer if the doctor thinks it is necessary.

On Day -6 through Day -2, you will receive fludarabine 1 time each day by vein, over about 30 minutes each time.

On Days -5 and -4, you will receive cyclophosphamide 1 time each day by vein, over about 2 hours each time.

On Days -5 and -4, you will receive mesna 5 times per day by vein, over about 15 minutes each time. Mesna is given to protect your bladder from side effects that may be caused by cyclophosphamide.

Cyclophosphamide, fludarabine, and mesna will all be infused through the same indwelling catheter.

Infusion of NK cells:

On Day 0, you will receive the NK cells by vein, preferably through an indwelling catheter. If you do not have an indwelling catheter, you may receive the infusion intravenously (IV -- by vein). The doctor will decide the amount of NK cells to be infused, which will affect how long the infusion lasts. Usually the infusion should last less than 1 hour.

To help prevent an allergic reaction to the infused NK cells (such as fever and chills), you will receive Benadryl (diphenhydramine) by vein, over 15-30 minutes, and Tylenol (acetaminophen) by mouth. You will also receive fluids by vein to help decrease the risk of kidney damage. If the study doctor thinks it is necessary, you may also receive a steroid to help prevent side effects.

If the doctor thinks that you are not eligible to receive the NK cell infusion on Day 0, you will be taken off study without receiving the donor's NK cells. The collected NK cells will be thrown away.

This study allows eligible recipients under the age of 2 years of age to participate. You and/or a caregiver will be trained how to give the IL-2 injections to yourself. This drug will be injected under the skin for 9 doses. You will take 3 doses per week over a 3-week period after receiving the NK cells.

Measuring NK Cell Survival Through Blood Test:

On Day 0 (before the NK cell infusion and again 2 hours later), and 1 time on each of the following days: Days 2, 7, 14, 21, and 28, blood (about 4 teaspoons each time) will be drawn and tested to see how long the NK cells survive in your body.

If the disease gets worse or the infused NK cells can no longer be seen, this blood draw schedule may be stopped early.

Follow-Up Visits:

You will have follow-up visits at least 3 times per week during the first 3 weeks, and then 1 time about 28 days after your NK cell infusion. Then, you will have additional follow-up visits at about Months 2 and 3. At these visits, the following tests and procedures will be performed:

* You will have any changes in your medical history recorded.
* You will have a physical exam, including a measurement of your vital signs.
* Blood (about 2 tablespoons) will be drawn for routine tests.

On Days 14 and 28, and during Months 2 and 3, you will have a bone marrow biopsy and/or aspiration.

Length of Study:

You will remain on active study for up to 3 months following your NK cell infusion that you agree to have performed.

This is an investigational study. Cyclophosphamide, fludarabine, mesna, and IL-2 are FDA approved and commercially available. Cyclophosphamide and fludarabine are approved for treating leukemia in adults. IL-2 is FDA-approved, but not for the treatment of leukemia.

Epratuzumab is not FDA approved or commercially available. It is only being used in research.

The use of the CliniMACS machine and infusing NK cells combined with epratuzumab in patients with ALL are only being done in research.

Up to 10 recipients and 10 donors will take part in this study. All will be enrolled at The University of Texas (UT) MD Anderson Cancer Center.

Haploidentical Natural Killer (NK) Cells With Epratuzumab for Relapsed Acute Lymphoblastic Leukemia (ALL)

Adoptive Transfer of Haploidentical NK Cells in Combination With Epratuzumab for the Treatment of Relapsed Acute Lymphoblastic Leukemia

TTP calculated as average time, in months, from baseline to participants disease progression or death, monitored for a minimum of 1 year

Number of surviving participants without disease progression or death for any reason at one year post treatment.

M.D. Anderson Cancer Center

Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m\^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m\^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours.

Haploidentical NK Cells + Epratuzumab

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Anna Franklin, MD, Assistant Professor

Both participants had recurrent disease before single month assessment therefore no data was analyzed. Study was terminated early due to slow accrual.

Time to Progression (TTP)

Overall Survival (OS)

Overall Study

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Fludarabine 25 mg/m\^2 intravenous (IV) Daily Over 30 minutes Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2. Cyclophosphamide 60 mg/kg IV Daily Over 2 Hours On Days -5 and -4. Natural Killer Cell Infusion on Day 0. Mesna 12 mg/kg By Vein, Over about 15 minutes, 5 Times Per Day on Days -5 and -4. Interleukin-2 subcutaneously three times weekly for 9 total doses following NK Cell Infusion.

25 mg/m\^2 By Vein Daily Over 30 minutes Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2.

60 mg/kg By Vein Daily Over 2 Hours On Days -5 and -4

Natural Killer Cell Infusion

12 mg/kg By Vein, Over about 15 minutes, Five Times Per Day on Days -5 and -4.

Received under skin three times weekly for 9 total doses following NK Cell Infusion:

For patients weighing 45 kg or more, dose administered is 10 Million units three times weekly for 9 total doses. For patients less than 45 kg, dose administered is 5 Million units/m2 (max dose 10 Million units) three times weekly for 9 total doses.

Susan S. Kelly, MD

Primary:

Evaluate safety, feasibility, persistence, and anti-tumor effect of infused haploidentical donor-derived natural killer (NK) cells and low-dose interleukin-2 (IL-2).

Secondary:

* Quantification of cytokine levels;
* Assessment of NK cell immunophenotype and function.

Experimental Therapy:

NK cells are part of the immune system (the cells in the body that naturally fight disease and infection). NK cells can sometimes destroy tumor cells, and they may be better at destroying tumor cells when the NK cells are "mismatched" for certain proteins called human leukocyte antigens (HLA). This can be determined by looking at the donor's and the recipient's HLA types and by checking for other specialized proteins on the donor's NK cells (called killer immunoglobulin receptors \[KIR\]).

The NK cells will be collected from the donor's blood and then processed using an experimental device called a CliniMACS device. This device is designed to separate out the NK cells from the rest of the donor's collected white blood cells, using a special magnet. Before being infused into the recipient (you, if you choose to take part), the collected NK cells will be treated with a study drug called interleukin-2 (IL-2) in order to try to activate the NK cells' killing ability. You will also receive IL-2 injections to try to help the NK cells survive after infusion and possibly increase in number.

Screening Tests:

Within 28 days before you can start treatment on this study, you will have "screening tests" to help the study doctor decide if you are eligible to take part in this study. The following tests will be performed:

* To check the status of the disease, you will have bone marrow aspirations and biopsies performed. To collect a bone marrow biopsy and aspirate, up to 2 areas of the hip bone are numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a needle.
* For another check of the status of the disease, you will most likely need to have computed tomography (CT) scans of the neck, sinuses, chest, stomach area (abdomen), and hip area (pelvis), and the brain.
* If the doctor thinks it is necessary, the status of the disease will also be checked with standard/routine tests such as positron emission tomography (PET) scans, iodine-131-meta- iodobenzylguanidine (MIBG -- a test that uses injected radioactive material and a special scanner to locate a tumor), and/or a bone scan.
* To measure your heart rate and level of oxygen in the blood, you will have a pulse oximetry test. This test uses a clothespin-shaped device that goes on the finger for about a minute.
* You will have a physical exam, including measurement of vital signs (blood pressure, heart rate, temperature, and breathing rate).
* Your medical history will be recorded.
* Blood (about 4 tablespoons) will be drawn for routine tests and to check for diseases (infections such as the human immunodeficiency virus \[HIV\]). You will be told the results of this test for any diseases. If you have one of these infections, you will probably not be able to participate in this study.
* Urine or an additional 4 teaspoons of blood may also be drawn for other routine tests to check the disease status.
* Blood (up to 6 tablespoons) will be drawn and used to test for HLA and KIR typing, and you and the donor will be told the results of this test.
* Females who are able to have children must have a negative serum pregnancy test (as part of the blood sample described above, or possibly an additional 1 teaspoon).

These screening tests would also need to be repeated before an additional NK cell infusion for this study, in order to see if you continue to be eligible to receive one. This will be described further below.

Identifying an Eligible Donor:

Your relative, who must share half of your HLA genes to be eligible for the study, will be tested to see if his or her KIR molecule has the "mismatch" that researchers believe should help the donor's NK cells to target the tumor cells in your body.

The donor's blood will also be tested to guard against the possibility of transmitting an infection to you during the NK cell infusion.

Samples of the donor's blood will be used to help researchers develop future tests that will be used to track how long the infused NK cells survive and function in recipients' bodies. In order to help track the cells after infusion, researchers prefer (but do not require) that if you are a female recipient, your donor should be male and if you are a male recipient, your donor should be female.

Conditioning Phase:

If you are found to be eligible to take part in this study, you will start the "conditioning" phase of this study within 4 weeks after the screening tests. Over the course of 6 days, you will receive chemotherapy with cyclophosphamide and fludarabine to weaken your immune system in order to help the survival of the infused NK cells, and then mesna to protect your bladder from side effects that cyclophosphamide may cause.

Cyclophosphamide, fludarabine, and mesna will preferably be infused through an indwelling catheter (a tube that remains in a vein, such as tunneled in the arm or through the chest). If you already have an indwelling catheter in place, you will not need to have a new one placed. If a new catheter is needed, however, you will be asked to sign a separate informed consent form for its placement.

The Conditioning schedule is the following:

-Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2, you will receive fludarabine by vein, over about 30 minutes.

On Days -5 and -4, you will receive cyclophosphamide by vein, over about 2 hours each time.

-Five times per day on Days -5 and -4, you will receive mesna by vein, over about 15 minutes each time.

Infusion of NK Cells:

On Day 0 you will receive the NK cells by vein, preferably through an indwelling catheter. The doctor will decide what amount of NK cells will be infused, which will affect how long the infusion lasts, but usually it lasts less than 1 hour.

To help prevent an allergic reaction to the infused cells (such as fever and chills), you will receive Benadryl (diphenhydramine) by vein, over 15-30 minutes, and Tylenol (acetaminophen) by mouth. You will also receive fluids by vein to help decrease the risk of kidney damage.

You or a caregiver will be trained in how to perform the IL-2 injections yourself. This drug will be injected under the skin for 9 doses over the course of 3 weeks.

If the doctor decides you are not eligible to receive the NK cell infusion on Day 0, you will be taken off study without receiving the donor's NK cells. The collected NK cells will be thrown away.

Blood Test for Measuring NK Cell Survival:

Blood (up to 4 teaspoons each time) will be drawn and tested to see how long the NK cells survive in your body. This blood will be drawn on Day 0 (before the NK cell infusion and again 2 hours later) and on Days 2, 7, 14, 21, and 28. (It is possible that this blood draw schedule will stop earlier if the disease gets worse or the infused NK cells can no longer be seen.)

Possible Additional NK Cell Infusion:

If the neuroblastoma responds and you did not suffer a new intolerable side effect from the NK cells, then you may be eligible to receive 1 additional infusion of NK cells. If so, the rest of the study procedures would be the same as before (the screening tests to determine your eligibility, the requirement that the donor still be eligible, the Conditioning Phase with chemotherapy, the IL-2 injections, and the blood tests). You must use the same donor as before, if he or she is still eligible.

Hospitalization:

So that you can be monitored for side effects, you will need to stay in the hospital from Day -6 until after the NK cell infusion (or longer if medically necessary).

Follow-Up Visits:

After your final NK cell infusion, you will return for follow-up visits at least 3 times a week during the first 3 weeks. Then you will return for follow-up visits at around Day +28 and again 3 months after the last NK cell infusion. Following your 3 month visit, you will be asked to return for follow-up visits every 3 months up until one year after the last NK cell infusion. Below is a schedule of what will be done at each visit:

* Initial 3 weeks post infusion (3 times per week):
* Any changes in your medical history will be recorded, and a physical exam will be performed.
* Blood (up to 2 tablespoons) will be drawn for routine tests.

Day 28, at 3, 6, 9, and 12 months after infusion visits:

* Any changes in your medical history will be recorded, and a physical exam will be performed.
* Blood (up to 2 tablespoons) will be drawn for routine tests.
* Urine or an additional 4 teaspoons of blood may be drawn for other routine tests to check the disease status.
* CT scans of the neck, sinus, chest, abdomen, and pelvis will be performed, and a CT of the brain may also be performed if the study doctor feels it is needed.

MIBG scan may be performed if your tumor was positive on MIBG scan in the past or if your doctor feels it is needed.

-Bone marrow biopsies/aspirations may be performed once in the first month, then may be done at each visit if you had neuroblastoma in your bone marrow at the time you started on the study or if your doctor feels it is necessary.

PET scan and/or bone scan may be performed sometime in Months 2 or 3, and again in months 6 -12 if your doctor feels it is needed.

This is an investigational study. Cyclophosphamide, fludarabine, mesna, and IL-2 are commercially available but not FDA approved for use in neuroblastoma. Injecting IL-2 under the skin is not FDA approved for use in increasing the production of NK cells. The CliniMACS device is not commercially available or FDA approved. Infusing NK cells in patients with neuroblastoma is also considered experimental. At this time and for this purpose, NK cell infusions and the CliniMACS device are being used in research only.

Up to 10 recipients and 10 donors will take part in this study. All will be enrolled at M. D. Anderson.

Haploidentical Natural Killer (NK) Cells in Patients With Relapsed or Refractory Neuroblastoma

Study to Infuse Haploidentical Natural Killer Cells in Patients With Relapsed or Refractory Neuroblastoma

Neuroblastoma International Response Criteria: Complete Response (CR): No evidence of disease (primary and metastasis) clinically \& radiographic studies, (homovanillic acid (HVA)/vanillylmandelic acid (VMA) normal). Very Good Partial Response (VGPR): \>90% reduction in primary tumor, resolution all metastatic tumor except bone. No new bone lesions and improvement on scan of all pre-existing lesions; HVA/VMA decreased \>90%. Partial Response (PR): 50-90% reduction primary and all measurable metastatic lesions, 0-1 bone marrow samples with tumor; scans of bone lesions same as VGPR. HVA/VMA decreased 50-90%. Mixed Response (MR): \> 50% reduction any measurable disease (primary or metastases); no new lesions; \<25% increase in any existing lesion (exclude bone marrow evaluation). No Response (NR): No new lesions; \< 25% increase in existing lesion. Progressive Disease (PD): Any new lesions. Increase \<25% in measurable lesion, previous negative bone marrow positive for tumor.

Feasibility of an infused allogeneic donor NK cell product and IL-2 following a cyclophosphamide and fludarabine preparative regimen to treat relapsed neuroblastoma after autologous peripheral blood stem cell (PBSC) transplant where feasibility is defined as being able to infuse NK cells on day 0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Haploidentical Natural Killer (NK) Cells With Epratuzumab for Relapsed Acute Lymphoblastic Leukemia (ALL)	NCT00941928	Leukemia Pediatric Cance...	Epratuzumab Fludarabine Cyclophosphamid... Mesna Infusion of NK ... Interleukin-2	-	M.D. Anderson Cancer Center
Haploidentical Natural Killer (NK) Cells in Patients With Relapsed or Refractory Neuroblastoma	NCT00698009	Neuroblastoma	Fludarabine Cyclophosphamid... Natural Killer ... Mesna Interleukin-2	-	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for infusion of nk cells