Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Leukemia

Lymphoma, Non-Hodgkin

Leukemia, Myeloid

Leukemia, Lymphoid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Lymphosarcoma

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Myeloproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Rituximab

Melphalan

Thiotepa

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Antimetabolites

Two Unmanipulated Cord Blood units. Rituxan 375 mg/m2 by vein for patients with CD20 + malignancies. Melphalan 140 mg/m2 by vein on Day -8. Thiotepa 5 mg/Kg by vein on Day -7. Fludarabine 40 mg/m2 by vein on Days -6 to -3.

One Unmanipulated and One Expanded Cord Blood Unit. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.

Transplantation of Two Unmanipulated Cord Blood Units.

Expanded allogeneic cord blood (CB)

Transplantation of One Unmanipulated and One Expanded Cord Blood Unit.

One Unmanipulated and One Expanded Cord Blood Unit

375 mg/m2 by vein on Day - 9 for patients with CD20 + malignancies.

Rituxan

10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg).

Total body irradiation (TBI) given on Day -1 at 2 Gy.

Total body irradiation (TBI)

Simrit Parmar, MD

The goal of this clinical research study is to learn if combining cord blood units to make the cells "take" faster in recipients will help to improve the results of cord blood transplants.

Cord blood is a source of blood forming cells that can be used for transplantation. The major problem with this type of transplant is the small number of blood forming cells available in each cord unit, which may delay the "take" of the graft in the recipient. Two strategies may be used to try to overcome this problem. One method is the combination of 2 units of cord blood and the other is the growing of the cord blood cells in the laboratory before they are transplanted in order to increase their number.

Participants will be randomly assigned (as in the toss of a coin) to one of two groups. If you are assigned to Study Arm 1, you will receive two cord blood units combined without growing the cells in the laboratory. If you are assigned to Study Arm 2, you will receive one cord blood unit combined with one cord blood unit which will be grown in the laboratory for two weeks before you receive it. Neither you nor your doctors will know in advance to which arm you will be assigned.

Placement of central venous catheter for collection of "back-up" stem cells:

Before you have back-up stem cell collected or you receive chemotherapy, you will require placement of a hollow plastic tube (catheter) into a large vein inside your body. This catheter will be used to draw blood and to give medications and fluids. The catheter is inserted through the skin in the upper chest and extends into the right side of your heart. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for it.

Collection of back up stem cells:

Because collecting additional cells from the donor of the cord blood will not be possible if the transplant with cord blood fails, a back up blood or bone marrow sample will be collected from you and frozen before the high dose chemotherapy begins.

Peripheral blood progenitor cell collection (Leukapheresis):

Before collection of the blood stem cells, you will be treated with a drug called granulocyte colony stimulating factor (G-CSF), which will cause the important stem cells in the marrow to move the peripheral blood where they will be collected. This medication is given as a shot under the skin once a day for 3 - 7 days, at which time your blood stem cells will be collected from your central catheter during a 3-4 hour out-patient procedure. In some cases where a "good vein" cannot be accessed, a silicone venous catheter may be needed to collect your blood.

Bone Marrow Collection:

If the leukapheresis cannot be performed successfully, you will receive general anesthesia in the operating room and will have multiple needle sticks of the hip bones in order to collect bone marrow. Only a small part of your bone marrow (\<5%) will be taken.

Selection of another donor as the alternate source of stem cells:

If your bone marrow or back-up blood stem cells cannot be collected, a family member whose bone marrow is the closest match will be chosen as the back up donor. The potential donor would have testing performed to assure that he/she is eligible to donate.

High-dose therapy:

Your bone marrow transplant doctors will give you one of four chemotherapy treatments, which are discussed below. If you have acute lymphoblastic leukemia, lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, acute myelogenous leukemia, myelodysplastic syndrome, chronic eosinophilic leukemia or chronic myelogenous leukemia, are less than 61 years old, and can receive high-dose chemotherapy, you may be assigned to Treatment Regimen #1 - fludarabine-thiotepa-melphalan. Patients with ALL may be assigned to Treatment Regimen #1 or #3, depending on your doctor's evaluation, age and physical fitness.

You will receive melphalan as a single dose on Day -8, thiotepa as a single dose on Day -7, followed by fludarabine given once a day for 4 days in a row (Days -6 through -3. Rituximab may be given on Day -9 if appropriate for your disease. Day 0 is the day of transplantation, so the negative day numbers are used to label the treatment days before transplant.

If you have any of the diseases listed above, have had a bone marrow transplant in the past, or have a physical that makes you less likely to tolerate high-dose therapy well, you will be in the less aggressive Treatment Regimen #2, Fludarabine, Cyclophosphamide and low dose total body irradiation. The fludarabine will be given on Days -6, -5, -4, and -3. The cyclophosphamide will be given on Day -6. Irradiation will be given on day -1. Rituxan may be given on Day -7 if appropriate for your disease.

If you have acute lymphoblastic leukemia, are 50 years old or younger, and your doctors have decided that full-dose Total body irradiation is the best treatment for you, you will be assigned to Treatment Regimen #3 - total body irradiation-VP16. You will receive total body irradiation on Days -7,-6, -5 and -4, followed by VP16 (also known as etoposide) as a single dose on Day -3. Rituximab may be given on Day -8 if appropriate for your disease.

All chemotherapy, fluids and other medications that must be given by vein will be infused through your catheter. Once the backup stem cells are collected, all patients will be admitted to the hospital on Day -9 to begin receiving fluids. Chemotherapy may be stopped if intolerable side effects occur.

Expansion of expanded cord blood:

On Day -14, if you are in Treatment Group 2, one of your two cord blood units will be thawed and treated in the MD Anderson Stem Cell Laboratory with vitamin-like growth factors for 2 weeks before they are given back to you on day zero as described below. A small amount of cord blood cells (less than 3%) will be used for laboratory procedures that measure the quality of the product.

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.

Transplantation of cord blood:

If you are in Treatment Group 1, two days following completion of high-dose therapy (Day 0), both units of cord blood will be thawed and infused (one at a time) through your catheter. Each unit will take about 30 minutes to infuse. Patients in Treatment Group 2 will receive one unit of cord blood that did not go through expansion of cells, followed by infusion of the unit that was grown in the laboratory for 14 days.

Graft versus host disease (GVHD) preventive therapy:

GVHD results from a reaction of the transplanted cord blood cells against certain tissues in your body. In an attempt to prevent or decrease the severity of GVHD, you will receive two drugs.

Mycophenolate mophetyl (MMF) pills will be given starting three days before your transplant, and will be continued until day 30 after the cord blood transplant. If you cannot take pills, the drug can be given through your catheter. If you develop GVHD, the use of MMF may be prolonged.

Tacrolimus will be given as a 24 hour continuous infusion over 3-6 weeks. Around Day 30 or 40 (after engraftment), the tacrolimus will be changed to pills given daily for 6-9 months. The number of tacrolimus pills may vary according to the blood levels of the drug, but usually are between 1 - 5. This medicine is used for 6-9 months (longer if chronic GVHD occurs).

You will remain on study as long as your disease does not return. If your disease returns, you will be taken off study and you may be offered participation in another study or be treated outside of this study.

Follow-up after transplant:

After you leave the hospital, you will be seen regularly in the Department of Blood and Marrow Transplantation at MD Anderson. The frequency of the visits may vary, but may be as often as daily. Blood (1-2 tablespoons) and urine tests will be performed. The frequency of blood tests may also vary, but may be performed daily. Patients will need a bone marrow sample collected before transplant and at 1 month, 3-4 months, and 5-7 months after transplant. After that, bone marrow samples will be collected once a year, indefinitely. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anaesthetic and a small amount of bone marrow is withdrawn through a large needle. Patients with lymphomas and Hodgkin's disease will need CT scan of the thorax, abdomen, and pelvis performed before transplant and then at 1 month, 3-4 months, and 5-7 months after the transplant. After that it will be done yearly.

This is an investigational study. All treatment drugs are FDA approved and commercially available.

A total of 110 patients may take part in this study. All will be enrolled at MD Anderson.

Randomized Double Cord Blood Transplant Study

Randomized Trial of Unmanipulated Versus Expanded Cord Blood

Engraftment is defined as a sustained ANC \> 0.5 x 10\^9/L for at least 3 consecutive days. Engraftment date is the first of the 3 days with sustained absolute neutrophil count (ANC) \>/= 0.5 x 10\^9/L.

Engraftment defined as a sustained absolute neutrophil count (ANC) \> 0.5 x 10\^9/L for at least 3 consecutive days. Engraftment Failure defined as ANC \<500/ul by day +42 and participant has no evidence of donor chimerism on bone marrow examination.

Number of participants who display features of acute GVHD within 100 days of transplant.

Number of participants who present GVHD post-transplant and display features of chronic GVHD. Diagnostic and distinctive features of chronic GVHD are present. There are no features of acute GVHD.

The severity of acute GVHD is determined by an assessment of the degree of involvement of the skin, liver, and gastrointestinal tract. The stages of individual organ involvement is assessed using Glucksberg grade (I-IV) where Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

National Cancer Institute (NCI)

Cellgenix

M.D. Anderson Cancer Center

Transplantation of Two Unmanipulated CB units. Rituxan 375 mg/m2 IV Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3.

Un-Manipulated CB Arm

Transplantation One Unmanipulated and One Expanded CB Unit. Rituxan: 375 mg/m2 IV on Day - 9 for CD20 + malignancies. Fludarabine 40 mg/m2 IV on Days -6 to -3. Cyclophosphamide 50 mg/kg IV on Day -6. Mesna 10 mg/kg IV before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). TBI Day -1 at 2 Gy.

Expanded CB Arm

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Simrit Parmar, MD/Associate Professor, Stem Cell Transplantation

Time To Neutrophil Engraftment

Number of Participants With Engraftment

Acute GVHD percentage calculated using engrafted participants only (n=89; expanded 44; un-manipulated 45)

Rate of Acute Graft Versus Host Disease (GVHD)

Overall Chronic GVHD

Limited

Extensive

Chronic GVHD percentage calculated using engrafted patients and alive after 100 days (n=77; expanded 40; unmanipulated 37)

Rate of Chronic GVHD

Grade ≤ 2

Grade ≥ 3

No GVHD

For the Acute GVHD the analysis was performed on patients with GVHD in the first 100 days.

Number of Participants Severity of Acute GVHD by Treatment Arm

Transplantation of Two Unmanipulated Cord Blood (CB) units. Rituxan 375 mg/m2 by vein (IV) Day -9 for participants with CD20 + malignancies. Melphalan 140 mg/m2 IV on Day -8. Thiotepa 5 mg/Kg IV on Day -7. Fludarabine 40 mg/m2 IV on Days -6 to -3.

Expanded allogeneic cord blood (CB): Transplantation of Two Unmanipulated Cord Blood Units.

Double Cord Blood Transplant Group (Un-Manipulated)

One Unmanipulated and One Expanded Cord Blood Unit. Rituxan: 375 mg/m2 by vein on Day - 9 for patients with CD20 + malignancies. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy.

One Expanded Cord Blood Transplant Group (Expanded)

Overall Study

Anti-Infective Agents

Analgesics

Aldesleukin

Interleukin-2

Epratuzumab

Analgesics, Non-Narcotic

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.

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

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)

Sclerosis

Hodgkin Disease

Hodgkin Lymphoma

Carboplatin

Etoposide

Ifosfamide

Bortezomib

Etoposide phosphate

Isophosphamide mustard

Enzyme Inhibitors

Bortezomib + ICE (Ifosfamide, Carboplatin, Etoposide):

Bortezomib 1.0 mg/m\^2 intravenous (IV) over 5 Seconds on Days 1 and 4; + ICE (Ifosfamide 5 Gm/m\^2 IV continuous infusion on Day 1, Carboplatin 5 AUC IV over 1 Hour Day 1, Etoposide 100 mg/m\^2 IV over 2 Hours Days 1-3) + Mesna 5 mg/m\^2 IV continuous infusion Day 1; 2 Gm/m\^2 IV continuous infusion over 12 Hours.

1.0 mg/m\^2 by Vein Over 5 Seconds on Days 1 and 4

100 mg/m\^2 By Vein Over 2 Hours On Days 1-3

5 Gm/m\^2 By Vein Continuous Infusion Over 24 Hours On Day 1

5 mg/m\^2 IV continuous Infusion over 24 Hours On Day 1; 2 Gm/m\^2 IV continuous infusion over 12 hours starting after completion of Ifosfamide + Mesna 24 hour continuous infusion

Michelle A. Fanale, MD

Primary Objectives:

1. To determine the toxicity profile of multiple doses of bortezomib when given with ICE in patients with relapsed and refractory classical Hodgkin lymphoma (HL).
2. To determine the maximum tolerated dose (MTD) of bortezomib when given in combination with ICE chemotherapy in patients with relapsed and refractory classical Hodgkin lymphoma (HL).

Secondary Objectives:

- To determine the overall response rate and complete response rate in patients with relapsed and refractory classical Hodgkin lymphoma (HL).

Bortezomib is designed to block a protein that plays a role in cell function and growth, which may cause cancer cells to die.

ICE is a combination of chemotherapy drugs that, together, may work more effectively at causing cancer cells to die by stopping cells from dividing.

Mesna is a drug that protects bladder cells from damage by the chemotherapy drug ifosfamide. It is used to decrease the risk of bleeding in the bladder.

Before you can start taking the drugs on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. These tests may be performed within 28 days of starting the study drugs. If you have had some of these exams, tests, or procedures performed recently, they may not need to be repeated. This will be for your study doctor to decide. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight. You will have x-rays and a bone marrow biopsy 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. You will have a computed tomography (CT) scan of your abdomen, chest, and pelvis and a positron emission tomography (PET) scan. Blood (about 2-3 tablespoons) will be drawn for routine tests. Women who are able to have children must have a negative blood (about 1 teaspoon) pregnancy test within 1 month before starting therapy on this study. Because taking part in this study requires that participants' ability to fight off infections be normal, you will have blood drawn (about 1-2 tablespoons) to be tested for HIV within 6 months before starting therapy on this study. If your HIV test results are found to be positive, you will not be able to take part in this study.

All participants will receive bortezomib as a fixed dose, which will not change unless any intolerable side effects occur. At the start of this study, 3 participants will be given a dose of bortezomib. If this dose does not cause intolerable side effects, the dose will be increased as new participants take part in this study. There will be a total of 3 groups (with 3-6 participants per group) entered at increasing dose levels. The dose of bortezomib you receive will depend on when you join this study.

If you are found to be eligible to take part in this study, you will receive bortezomib plus ICE by vein. You will receive bortezomib, on Days 1 and 4, over 5 seconds. The ICE regimen will be given as a continuous infusion over different times as follows. On Day 1, you will receive ifosfamide and mesna over 24 hours. On Day 2, you will receive mesna over 12 hours and carboplatin over 1 hour. On Days 1-3, you will receive etoposide over 2 hours. This schedule for bortezomib plus ICE is considered 1 cycle (2 weeks) and will be repeated every 14 days.

You may have 3-6 cycles of the study drugs, depending on your tolerance of the drugs and the status of the disease. If the disease gets worse or you experience any intolerable side effects, you will be taken off this study.

Blood (about 2-3 tablespoons) will be drawn once a week for routine tests. You will have a study visit before the start of each 2-week cycle. During these visits, you will have a brief questionnaire that will ask about specific side effects you might be experiencing. It should take about 5 minutes to complete this questionnaire.

After completing 3 cycles, you will return for CT scans, bone marrow biopsies (if they were positive for disease before you began on this study), and a PET scan to check the status of the disease.

After completing 3 cycles (if the disease did not worsen and intolerable side effects did not occur), you may continue on this study for 3 more cycles. During Cycles 4-6, you will have the same scans and blood tests as mentioned above.

After completing this study, for every 3-4 months on an indefinite basis, you will have follow-up visits. During these visits, you will have blood drawn (about 2-3 tablespoons) for routine tests. You will also have the same scans that were performed during the screening visit.

This is an investigational study. Bortezomib and ICE are FDA approved and commercially available. The combination of bortezomib plus ICE is considered investigational and authorized for use in research only.

Up to 18 patients will take part in this study. All will be enrolled at M. D. Anderson.

Velcade Plus ICE for Patients With Relapsed Classical Hodgkin Lymphoma

Phase-I Study of Bortezomib (VELCADE) Plus ICE (Ifosfamide, Carboplatin, Etoposide) for Patients With Relapsed Classical Hodgkin Lymphoma

MTD dose escalation stops either at the highest indicated dose of bortezomib (1.5 mg/m2), or when a Dose limiting toxicity (DLT) has been observed in at least one third of the patients at any dose level.

Millennium Pharmaceuticals, Inc.

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Methotrexate

Lenograstim

Tacrolimus

Thymoglobulin

Busulfan

Clofarabine

Antilymphocyte Serum

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Calcineurin Inhibitors

Folinic Acid

Folate

Vitamin B9

Pre-transplant conditioning regimen:

Thiotepa (Thio) + Clofarabine (Clo) + Busulfan (Blu) + Allogeneic Stem Cell Transplantation (Allo SCT) + ATG + G-CSF

Post haploidentical stem cell transplant participants:

Cyclophosphamide 50 mg/kg by vein on Days + 3 and + 4. Mesna 10 mg/kg by vein just prior to the first dose of cyclophosphamide, repeated every 4 hours for a total of ten (10) doses.

5 mg/kg through a central venous catheter (CVC) over 2 hours on Day -8.

40 mg/m\^2 through a central venous catheter (CVC) over 1 hour daily on 4 consecutive days (Days -6 through -3).

Test dose of 0.5 mg/kg through a central venous catheter (CVC)over 30 minutes on Day -7.

High dose 5,000 µMol-min through a central venous catheter (CVC) over 3 hours on Days -5, -4, and -3.

Infusion of stem cells through through a central venous catheter (CVC) On Day 0.

Allogeneic Stem Cell Transplantation

1.25 mg/kg by vein on Day -4 and 1.75 mg/kg on Day -3.

Thymoglobulin (ATG)

5 µg/kg Injection under the skin once a day, starting 1 week after transplant, until blood cell levels return to normal.

G-CSF (Filgrastim)

Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily, to be changed to oral dosing when tolerated. Tacrolimus is to be tapered as indicated after transplant day 90, if no GVHD is present. Tacrolimus is adjusted trough level of 5-15 ng/mL.

5 mg/m2 by vein on Days 1, 3 and 6 and Day +11 post transplant. The Day 11 methotrexate dose may be held as indicated if mucositis is present.

Post haploidentical stem cell transplant participants: 50 mg/kg by vein on Days + 3 and + 4.

Post haploidentical stem cell transplant participants: 10 mg/kg by vein just prior to the first dose of cyclophosphamide, repeated every 4 hours for a total of ten (10) doses.

Kris M. Mahadeo, MD

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.

The goal of this clinical research study is to learn if thiotepa, busulfan, and clofarabine, when given before an allogeneic (bone marrow , blood, or cord blood cells) or haploidentical (bone marrow) stem cell transplantation can help to control cancers of the bone marrow and lymph node system. The safety of this treatment will also be studied.

This is an investigational study. Thiotepa and clofarabine are FDA approved and commercially available for the treatment of leukemia. Busulfan is FDA approved and commercially available for use in stem cell transplantation. The combination of thiotepa, clofarabine, and busulfan together with a stem cell transplant is investigational.

Up to 60 participants will take part in this study. All will be enrolled at M. D. Anderson.

The Study Drugs:

Thiotepa and busulfan are designed to bind to DNA (genetic material of cells), which may cause cancer cells to die. They are commonly used in stem cell transplants.

Clofarabine is designed to interfere with the growth and development of cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will begin receiving the study drugs before you receive the stem cell transplant.

The days before you receive your stem cells are called minus days, such as Day -2 and Day -1. The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days, such as Day +1 and Day +2.

On Day -8 (8 days before you receive the stem cell transplant), you will receive thiotepa through a central venous catheter (CVC) over 2 hours. 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 to you in more detail, and you will be required to sign a separate consent form for this procedure.

On Day -7, you will receive busulfan through a CVC. This dose of busulfan is a low level "test" dose to check how your blood levels change over time. This information will be used to decide the next dose level of busulfan.

Blood (about 1 teaspoon each time) will be drawn 6-11 times total over Days -7 and -5 for pharmacokinetic (PK) testing. PK testing measures the amount of busulfan in the body at different time points. This PK testing will be done to find the dose of busulfan needed for your body size on the other days that you receive busulfan. A heparin lock line will be placed in a vein to lower the number of needed sticks performed for draws. If you cannot have the blood level tests performed for any reason, you will receive the standard busulfan dose.

On Days -6, -5, -4, and -3, you will receive clofarabine through a CVC over 1 hour.

On Days -5, -4, and -3, you will receive busulfan through a CVC over 3 hours.

If you will receive stem cells from a donor whose cells do not match your own cells closely, on Days -4 and -3 you will also receive antithymocyte globulin (ATG) by vein over 4 hours. This will help to reduce the risk of your body rejecting the transplant. If your transplant will involve haploidentical stem cells, you will not receive ATG on Days -4 and -3.

On Days -2 and -1, you will "rest," which means you will not be given any drugs, but your CVC will remain in place.

If thiotepa is not available:

If thiotepa is not available, or if you doctor thinks it is in your best interest, you will receive the following study drugs and total body irradiation (TBI) before you receive the stem cell transplant. TBI involves the delivery of high doses of radiation designed to destroy cancer cells and/or lower the immune system in order to lower the risk of the body rejecting the new stem cells.

Between Days -16 and -7, you will receive a low-level "test" dose of busulfan by vein over about 45 minutes to 1 hour. Test doses are used to study how your body breaks down busulfan and decide the dose of busulfan that you will receive. You may receive the test dose before Day -6 as an outpatient in the clinic, or on Day -6 as an inpatient in the hospital.

Blood (about 1 teaspoon each time) will then be drawn for PK testing up to 11 times over the 11 hours after the busulfan test dose and on Day -4. PK testing measures the amount of study drug in the body at different time points. The study staff will tell you more about the PK testing schedule.

A heparin lock line will be placed in your vein before the PK testing to lower the number of needle sticks needed for these draws. If for any reason it is not possible for the PK tests to be performed, you will receive the standard dose of busulfan.

On Day -7 or Day -6, you will be admitted to the hospital and given fluids through a CVC to hydrate you.

On Days -5, -4, -3, and -2, you will receive clofarabine through a CVC over 1 hour.

On Days -4, -3, and -2, you will receive busulfan through a CVC over 3 hours.

If you will receive stem cells from a donor whose cells do not match your own cells closely, on Days -3 and -2 you will also receive antithymocyte globulin (ATG) by vein over 4 hours. This will help to reduce the risk of your body rejecting the transplant. If your transplant will involve haploidentical stem cells, you will not receive ATG on Days -3 and -2.

On Day -1, you will receive TBI one time.

Stem Cell Transplant:

On Day 0, you will have an allogeneic or haploidentical stem cell transplant through the CVC. Allogeneic stem cells come from a donor whose cells closely match your own cells. Haploidentical stem cells come from a donor whose cells do not match your own cells as closely, but they are specially processed to help prevent graft versus host disease (GVHD).

Receiving stem cells is similar to receiving a blood transfusion. The time required to receive the stem cells will depend on the type of cells you are receiving. Receiving cord blood stem cells can take several minutes. Receiving bone marrow and blood stem cells may take several hours.

You will receive G-CSF (filgrastim) (which helps to produce white blood cells) as an injection under the skin once a day, starting 1 week after the transplant, until your blood cell levels return to normal.

You will receive drugs (mycophenolate mofetil (MMF), tacrolimus and/or methotrexate) to help prevent side effects, such as GVHD. You will receive methylprednisolone if you develop GVHD.

You will stay in the hospital for about 4 weeks after the stem cell transplantation.

If you had a haploidentical stem cell transplant, on Days 3 and 4 after your stem cell transplant, you will receive cyclophosphamide through a CVC over 3 hours. Mesna will be given by vein at the same time you are given each dose of cyclophosphamide, to help protect your bladder from bleeding.

Study Visits:

Beginning on Day -9, once a day while you are in the hospital:

* You will have a physical exam, including measurements of your vital signs.
* You will be asked if you have had any side effects.
* Blood (about 4 tablespoons) will be drawn to test your blood cell counts. Two (2) times a week, this blood will be also be used for routine tests.

After you are out of the hospital, 2 times a month until it has been 100 days after the transplant:

* You will have a physical exam, including measurements of your vital signs and weight.
* You will be asked if you have had any side effects.
* Blood (about 4 tablespoons) will be drawn for routine tests.

About 1, 3, 6, and 12 months after the transplant, blood (about 4 tablespoons) will be drawn to check the status of the disease. You will also have bone marrow aspirations to check the status of the disease. You will also have a physical exam.

If the doctor thinks it is necessary, you may have extra tests and procedures.

Length of Study:

You will be on study for about 1 year. You will be taken off study if the disease gets worse or needs further treatment.

Follow-Up:

If you live close to M. D. Anderson, you will return to the clinical once every several months for a physical exam. At these visits, blood (about 3 teaspoons) will be drawn for routine tests.

You and/or your local doctor will be called every several months and asked about your health status and if the leukemia or MDS has come back.

Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies

The toxicities will be monitored and scored on a daily basis following the methods of Simon R. Practical Bayesian Guideline for Phase IIB Clinical Trials. A Bayesian stopping rule will be used to stop the trial if there is a 90% chance that the true toxicity rate exceeds the target toxicity rate of 0.25.

Kaplan-Meier product limit method to estimate the disease free survival.

Overall Survival Rate will be estimated using the Kaplan-Meier method.

Severity of toxicities graded according to the NCI Common Toxicity Criteria Adverse Effects (CTCAE) v3.0. Standard reporting guidelines followed for adverse events. Safety data summarized by category, severity and frequency.

Engraftment is most commonly defined as the first of three consecutive days of achieving a sustained peripheral blood neutrophil count of \>500 × 10\^6/L .

Relapse Rate will be estimated using the Kaplan-Meier method.

The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days

Conditioning Reg- Thiotepa, Busulfan, and Clofarabine

Age, Categorical

Two participants did not proceed to transplant no data were collected for those two participants

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Randomized Double Cord Blood Transplant Study	NCT00067002	Leukemia, Lymph... Leukemia, Myelo... Leukemia, Myelo... Lymphoma, Non-H...	Expanded alloge... One Unmanipulat... Rituxan Melphalan Thiotepa Fludarabine Cyclophosphamid... Mesna Total body irra...	1 Month - 80 Years	M.D. Anderson Cancer Center
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
Velcade Plus ICE for Patients With Relapsed Classical Hodgkin Lymphoma	NCT00439361	Hodgkin Lymphom... Lymphoma	Bortezomib Carboplatin Etoposide Ifosfamide Mesna	16 Years -	M.D. Anderson Cancer Center
Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies	NCT00857389	Stem Cell Trans... Leukemia Lymphoma	Thiotepa Clofarabine Busulfan Allogeneic Stem... Thymoglobulin (... G-CSF (Filgrast... Tacrolimus Methotrexate Cyclophosphamid... Mesna	- 60 Years	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
Study of Bortezomib in Combination With Cyclophosphamide and Rituximab	NCT00958256	Mantle Cell Lym... Lymphoma	Bortezomib Rituximab Cyclophosphamid... Mesna G-CSF	18 Years - 85 Years	M.D. Anderson Cancer Center
Concurrent Chemotherapy and Radiation Therapy for Newly Diagnosed Nasal NK Cell Lymphoma	NCT02106988	Lymphoma	Radiation Thera... Dexamethasone Etoposide phosp... Ifosfamide Mesna Carboplatin	18 Years -	M.D. Anderson Cancer Center
Chemotherapy Plus Ofatumumab Followed by G-CSF for Mobilization of Peripheral Blood Stem Cells in Patients With Non-Hodgkin's Lymphomas	NCT01329900	Lymphoma	Ofatumumab Ifosfamide Etoposide Mesna G-CSF Stem Cell Colle...	18 Years - 70 Years	M.D. Anderson Cancer Center
Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies	NCT00857389	Stem Cell Trans... Leukemia Lymphoma	Thiotepa Clofarabine Busulfan Allogeneic Stem... Thymoglobulin (... G-CSF (Filgrast... Tacrolimus Methotrexate Cyclophosphamid... Mesna	- 60 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for mesnex

Every month we try and update this database with for mesnex cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for mesnex

Every month we try and update this database with for mesnex cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mesnex cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.