Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Mantle Cell Lymphoma

Antineoplastic Agents

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Cyclophosphamide

Fludarabine

Fludarabine phosphate

Rituximab

Tacrolimus

Alemtuzumab

Immunosuppressive Agents

Immunologic Factors

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Alkylating Agents

Antineoplastic Agents, Immunological

Antimetabolites

Allogeneic Stem Cell Transplantation With Rituximab Containing Nonablative Conditioning Regimen: Cyclophosphamide 750 mg/m\^2 given intravenously on Day -3, 4 hours after completion of Fludarabine 30 mg/m\^2 given intravenously on Days -5 and -3 before transplantation. Rituximab 375 mg/m\^2 given intravenously on Days -13, -6 before transplantation and Days 16, 8 after transplantation.

Allo MUD \& MM = Allogeneic Stem Cell Transplantation, Matched unrelated donor or mismatched sibling donor transplantations: Cyclophosphamide 1000 mg/m\^2 given intravenously on Day -3, 4 hours after completion of Fludarabine 30 mg/m\^2 given intravenously on Days -5 and -3 before transplantation. Rituximab 375 mg/m\^2 given intravenously on Days -8, -1 before transplantation and Days 6, 13 after transplantation. Alemtuzumab 15 mg per day given intravenously days 1 through 3 after transplantation.

Matched Donors:

750 mg/m\^2 given intravenously on Day -3, 4 hours after completion of Fludarabine.

Unrelated or Mismatched Donors:

1000 mg/m\^2 given intravenously on Day -3, 4 hours after completion of Fludarabine.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

30 mg/m\^2 given intravenously on Days -5 and -3 before transplantation.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

Matched Donors:

375 mg/m\^2 given intravenously on Days -13, -6 before transplantation and Days 16, 8 after transplantation.

Unrelated/Mismatched Donors:

375 mg/m\^2 given intravenously on Days -8, -1 before transplantation and Days 6, 13 after transplantation.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

For development of disease progression or no response, immunomanipulation with Rituximab 375 mg/m\^2 given intravenously, then 1000 mg/m\^2 given intravenously weekly for 3 weeks, and taper off Tacrolimus dose over 2 weeks.

DLI = Donor Lymphocyte Infusion/Immunomodulation Post Transplantation Immunomodulation for patients with lymphoid Malignancies:

375 mg/m\^2 then 1000 mg/m\^2 weekly x 3 if immunomanipulation is undertaken for persistent disease.

Unrelated/Mismatched Donors:

15 mg per day given intravenously days 1 through 3 after transplantation.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

Allogeneic Stem Cell Infusion

Issa F. Khouri, MD, BS

1. To determine the safety and efficacy of non-myeloablative allogeneic stem cell transplantation using rituximab, cyclophosphamide, fludarabine as a preparative regimen for patients with advanced or recurrent mantle cell lymphoma.
2. To determine factors associated with response and durable remission in patients receiving rituximab, cyclophosphamide, and fludarabine in preparation for allogeneic stem cell transplantation.

MATCHED SIBLING TRANSPLANTS:

If you are found to be eligible to take part in this study, you will be admitted to the hospital to receive treatment. Two (2) chemotherapy drugs, fludarabine and cyclophosphamide, will be given each day for 3 days. The drugs will be given one at a time in a vein. Each treatment will take about 30 minutes. Fludarabine will be given first, and cyclophosphamide will be given 4 hours later. You will receive rituximab once a week for 4 weeks by vein over 4-8 hours. The first dose will starts one week before starting the chemotherapy.

Two days after finishing chemotherapy, you will receive a transplant of stem cells from a sibling. The stem cells will be infused into your vein. Seven days later, you will begin to receive a drug called granulocyte colony-stimulating factor (G-CSF). G-CSF helps the new stem cells do their normal work in the body;making new blood cells. You will receive G-CSF each day until your blood cell counts begin to recover to a certain level.

Sometimes the donor cells cause inflammation of the skin, liver and gut, and a reaction called graft-versus-host disease occurs. The drugs tacrolimus and methotrexate will be given to help decrease the risk of this. These drugs are also given through a vein before and after transplant . Tacrolimus will be infused two days before transplant and will continue to be given daily as a continuous infusion. Methotrexate will be given through the vein as a short infusion on Days 1, 3, and 6 after the transplant. Tacrolimus also comes in pill form, and you may switch to the pills when ready.

During your hospitalization, you will be examined daily, and blood (about 1 tablespoon) samples will be taken daily to evaluate your blood count levels, the function of your liver and kidneys, as well as electrolytes. This blood will also be used to measure tacrolimus levels and to look for any infections. You might be given blood transfusions if blood cell counts remain low.

MATCHED UNRELATED OR MISMATCHED SIBLING TRANSPLANTS:

Alemtuzumab is a drug that is designed to specifically attack some types of leukemia and lymphoma cells. In addition, it weakens the immune system, helping to prevent the rejection of donor marrow or stem cells.

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

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. This may increase the likelihood of the cells dying.

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

If you are found to be eligible to take part in this study, you will be admitted to the hospital for treatment. Alemtuzumab will be injected into your vein over a period of 4 hours. This will be done 3 days in a row (Days 1 to 3). Drugs diphenhydramine (Benadryl), solumedrol and acetaminophen (Tylenol) will be given in to decrease the risk of or ease side effects before each dose of the alemtuzumab.

You will also receive fludarabine and cyclophosphamide once a day for 3 days. They will be given on the same days as alemtuzumab. Both drugs will be given through a catheter (plastic tube) that extends into the large chest vein. The catheter will be left in place throughout treatment on this study. Some participants, depending on their type of disease, will also receive rituximab. Rituximab will be given 8 days before the transplant and then once a week for a total of 4 doses.

After completion of chemotherapy, you will receive TBI, and later on the same day, blood stem cells from a donor will be given through the catheter. G-CSF, a growth factor that promotes the production of blood cells, will be injected under the skin once a day until your blood cell counts recover to a certain level.

Blood tests (about 2 tablespoons each) , urine tests, bone marrow aspirations, and x-rays will be done as needed to track the effects of the transplant. The blood tests will be drawn daily while in the hospital and then at least twice weekly as an outpatient for the first 100 days. The CT scans and bone marrow studies will be done at 1, 3, 6, and 12 months and then every 6 months for at least 3 years after transplant. You may also have transfusions of blood and platelets as needed.

IMMUNOMODULATION POST NONABLATIVE STEM CELL TRANSPLANTATION FOR PATIENTS WITH LYMPHOID MALIGNANCIES:

You will receive treatment as an outpatient. You will receive rituximab over 4 - 8 hours through a vein once a week for 4 weeks. You will also get a boost of cells from the same donor from whom you received the original transplant. These additional cells will be infused through the vein (over 30 - 60 minutes) between the second and the third dose of rituximab. The infusion may have to be done later if cells were not available as scheduled.

Sometimes the donor cells cause inflammation of the skin, liver and gut, and a reaction called graft-versus-host disease occurs. If this happens, the drug tacrolimus and methotrexate will be given to help control this reaction. These medications are usually given by pills on a daily basis.

A boost with a higher number of cells may be infused once a month for 3 months if there is no graft-versus-host disease and if disease remains.

During treatment, you will be examined as needed, and blood samples (1 tablespoon once or twice a week) will be taken for routine tests. You may need to receive blood transfusions during this study if your blood cell counts remain low.

\*\*\*\*\*\*

About 40 patients will take part in this study, and all will be enrolled at M. D. Anderson.

Non-Myeloablative Allogeneic Stem Cell Transplantation

Allogeneic Stem Cell Transplantation With Rituximab Containing Nonablative Conditioning Regimen for Advanced/Recurrent Mantle Cell Lymphoma

Overall Survival defined as the number of participants living at day 100 following non-myeloablative allogeneic stem cell transplantation using rituximab, cyclophosphamide, fludarabine as a preparative regimen for participants with advanced or recurrent mantle cell lymphoma.

M.D. Anderson Cancer Center

Matched Sibling Transplant

Allo MUD & MM

Total

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Issa F. Khouri, MD/ Professor

Overall Survival at 100 Days Post Transplant (Number of Surviving Participants)

Overall Study

Hodgkin Disease

Hodgkin Lymphoma

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Gemcitabine

Methotrexate

Melphalan

Immunomodulating Agents

Lenograstim

Thymoglobulin

Antilymphocyte Serum

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Calcineurin Inhibitors

Folinic Acid

Folate

Vitamin B9

Gemcitabine 800 mg/m\^2 intravenous (IV) over 30 minutes for one day; Fludarabine 33 mg/m\^2 IV for 4 days; Melphalan 70 mg/m\^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.

Fludarabine 33 mg/m\^2 IV for 4 days; Melphalan 70 mg/m\^2 IV over 30 minutes for 2 days. Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation. If receiving transplant from matched unrelated donor (not blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant, infusion of stem cells on Day 0. Tacrolimus 0.03 mg/kg by vein over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.

800 mg/m\^2 IV over 30 minutes on Day -7 (1 day)

33 mg/m\^2 IV over 30 minutes Day -5 to Day -2 (4 days)

70 mg/m\^2 IV over 30 minutes on Day -3 to Day -2 (2 days)

2 mg/kg IV on Day -4 and Day -3 (2 days) before stem cell transplantation.

If receiving transplant from matched unrelated donor (not a blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant.

Antithymocyte Globulin

0.03 mg/kg beginning Day -2 by vein over 24 hours; when tolerable change to pill form given once daily for 3-4 months.

Starting 1 week after transplant (Day +7) given as injection under the skin once daily until blood cell levels return to normal.

Filgrastim (G-CSF)

5 mg/m2 by vein on Days +1, +3, +6, and +11 to decrease risk of GVHD.

Paolo Anderlini, MD

The goal of this clinical research study is to learn if fludarabine, melphalan and gemcitabine followed by transplantation of stem cells (blood-forming cells) as well as immune cells (lymphocytes), collected from a matched related (i.e. a sibling) or unrelated donor, or a mismatched related donor, can help to control Hodgkin's disease. The safety of the treatment will also be studied.

Central Venous Catheter:

If you choose to take part in this study, the chemotherapy, some of the other drugs in this study, and the stem cell transplant and immune cells will be given by vein through your central venous catheter (CVC). A CVC is a sterile flexible tube and needle that will be placed into a large vein while you are under local anesthesia. Blood samples will also be drawn through your CVC. The CVC will remain in your body during treatment. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.

Study Drug Administration:

The days before you receive your stem cells are called minus days, such as Day -2, 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, Day +2.

On Day -7, you will receive gemcitabine by vein over about 40-180 minutes.

On Day -6, you will be admitted to the hospital and given fluids by vein to hydrate you.

On Days -5 and -4, you will receive fludarabine by vein over about 30 minutes.

On Days -4 and -3, you will receive thymoglobulin, if you are receiving a transplant from a matched unrelated donor (not a blood relative), a mismatched related donor (a blood relative, but not a full match), you will also receive antithymocyte globulin (ATG)

On Days -3 and -2, you will receive fludarabine by vein over about 30 minutes and melphalan over about 30 minutes.

On Day -1, you will "rest" (not receive chemotherapy).

On Day 0, you will receive the donor's stem cells and immune cells by vein. The infusion will last anywhere from about 30 minutes to several hours. You may be given other standard drugs to help lower the risk of side effects. You may ask the study staff for more information about how the drugs are given and their risks. All participants are expected to need blood transfusions as part of this treatment.

Beginning on Day -2, tacrolimus will be given by vein over 24 hours to help lower the risk of graft-versus-host disease (GVHD). This will be changed to pills once you can tolerate swallowing pills. If no active cancer is detected and there is no GVHD, you will then swallow 1 or more tacrolimus pills a day for only about 3-4 months, instead of the usual period of 6 months. This is done to boost the donor immune system against the cancer.

Starting 1 week after the transplant (Day +7), you will receive filgrastim (G-CSF) as an injection under the skin 1 time each day until your blood cell levels return to normal. Filgrastim is designed to make white blood cells grow, which may help to fight infections.

On Days +1, +3, +6, and +11, you will receive methotrexate by vein to decrease the risk of GVHD.

If you have persistent but stable (not "growing") disease after transplant, you will have your immunosuppressive medications (tacrolimus, corticosteroids) stopped even before 4 months. If there is no response, you will receive an infusion of additional cells from your donor.

Study Visits:

About 30 days before receiving the stem cells, you will have computed tomography (CT) and/or positron emission tomography (PET) scans to check the status of the disease.

About every day until discharge, and then at least weekly:

* You will have a physical exam.
* Blood (about 4 tablespoons) will be drawn for routine tests.

Follow-Up Visits:

About 100 days after the transplant:

* You will have a physical exam.
* Blood (about 4 tablespoons) will be drawn for routine tests. Part of the blood sample may be used for chimerism analysis (determination of donor or recipient cells), if needed.
* At any point that your doctor thinks they are needed, you will have a bone marrow aspiration, chest x-rays, and CT and/or PET scans to check the status of the disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

About 6 months, 1 year, then annually after the transplant:

* You will have a physical exam.
* Blood (about 4 tablespoons) will be drawn for routine tests. Part of the blood sample may be used for chimerism analysis (determination of donor or recipient cells), if needed. Part of the blood will be used to check your thyroid function once a year.
* At any point that your doctor thinks they are needed, you will have a bone marrow aspiration, chest x-rays, and CT and/or PET scans to check the status of the disease.
* You may have lung function tests, if your doctor thinks it is needed.
* About 6 months after the transplant, you may have a biopsy, if your doctor thinks it is needed.
* About once a year, you will have an eye exam.

The above tests/procedures may be repeated more often, if you doctor thinks it is needed.

The study staff will also stay in contact with your local doctor to find out if the disease comes back and to check how you are doing.

Length of Treatment:

You will be on study for about 3 years. After 1 year, there is no study specific testing you will be required to complete. Your transplant doctor will perform routine standard of care follow-up that all patients receiving allogeneic stem cell transplantation receive.

You may be removed from the study early if the doctor thinks it is in your best interest, if the disease gets worse or comes back, if intolerable side effects occur, if you have graft failure (the transplanted cells do not grow), or if you are unable to follow study directions.

If for any reason you want to leave the study early, you must talk to the study doctor. It may be life-threatening to leave the study after you have started to receive the study drugs but before you receive the stem cell transplant because your blood cell counts will be dangerously low.

This is an investigational study. All of the drugs used in this study are FDA-approved and commercially available. Up to 70 patients will take part in this study. All will be enrolled at MD Anderson.

Allogeneic Blood Stem Cell Transplantation and Adoptive Immunotherapy for Hodgkin's Disease

Allogeneic Stem Cell Transplantation Followed By Adoptive Immunotherapy for Patients With Relapsed and Refractory Hodgkin's Disease

Transplant-related mortality defined as death from any cause in the first 100 days post-transplant in patients without active disease.

Fludarabine 33 mg/m\^2 IV Day -5 to Day -2 (4 days); Melphalan 70 mg/m\^2 IV over 30 minutes Day -3 to Day -2 (2 days). Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation Day 0. Tacrolimus 0.03 mg/kg IV Day -2 over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) subcutaneously once daily + Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.

Fludarabine + Melphalan

Gemcitabine 800 mg/m\^2 intravenous (IV) over 30 minutes Day -7; Fludarabine 33 mg/m\^2 IV Day -5 to Day -2 (4 days); Melphalan 70 mg/m\^2 IV over 30 minutes Day -3 to Day -2 (2 days). Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation Day 0. Tacrolimus 0.03 mg/kg IV Day -2 over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) subcutaneously once daily + Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.

Gemcitabine + Fludarabine + Melphalan

Age, Continuous

Clinical Research Operations Team, Office of VP Clinical Research

Transplant Related Mortality Rate

Fludarabine 33 mg/m\^2 IV Day -5 to Day -2 (4 days); Melphalan 70 mg/m\^2 IV over 30 minutes Day -3 to Day -2 (2 days). Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation Day 0. Tacrolimus 0.03 mg/kg IV Day -2 over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.

Gemcitabine 800 mg/m\^2 intravenous (IV) over 30 minutes Day -7; Fludarabine 33 mg/m\^2 IV Day -5 to Day -2 (4 days); Melphalan 70 mg/m\^2 IV over 30 minutes Day -3 to Day -2 (2 days). Antithymocyte Globulin 2 mg/kg IV for 2 days before stem cell transplantation Day 0. Tacrolimus 0.03 mg/kg IV Day -2 over 24 hours following infusion; beginning Day +7 Filgrastim (G-CSF) injection under skin once daily and Methotrexate 5 mg/m2 by vein on Days +1, +3, +6, and +11.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Non-Myeloablative Allogeneic Stem Cell Transplantation	NCT00525876	Lymphoma	Cyclophosphamid... Fludarabine Rituximab Alemtuzumab Allogeneic Stem...	- 70 Years	M.D. Anderson Cancer Center
Allogeneic Blood Stem Cell Transplantation and Adoptive Immunotherapy for Hodgkin's Disease	NCT00385788	Hodgkin's Disea...	Gemcitabine Fludarabine Melphalan Antithymocyte G... Allogeneic Stem... Tacrolimus Filgrastim (G-C... Methotrexate	- 65 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for allogeneic stem cell infusion