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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Matched Sibling Transplant | Experimental | 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 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival at 100 Days Post Transplant (Number of Surviving Participants) | 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. | 100 days post transplant |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Issa F. Khouri, MD, BS | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| UT MD Anderson Cancer Center website | View source |
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Out of the 49 participants enrolled, 13 were excluded, not assigned to part of the two intervention study groups.
Recruitment Period:1/27/2005 through 8/31/2010. All participant recruitment attempted at UT MD Anderson Cancer Center.
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| ID | Title | Description |
|---|---|---|
| FG000 | Matched Sibling Transplant | 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. |
| FG001 | Allo MUD & MM | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Matched Sibling Transplant | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Survival at 100 Days Post Transplant (Number of Surviving Participants) | 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. | Analysis was per protocol. | Posted | Number | participants | 100 days post transplant |
|
3 years and 3 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Matched Sibling Transplant | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic Reaction | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment | Tongue swelling |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Epistaxis | General disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Issa F. Khouri, MD/ Professor | UT MD Anderson Cancer Center | celsaenz@mdanderson.org |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D020522 | Lymphoma, Mantle-Cell |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D000069283 | Rituximab |
| D000074323 | Alemtuzumab |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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|
|
| Fludarabine | Drug | 30 mg/m^2 given intravenously on Days -5 and -3 before transplantation. (Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0) |
|
|
| Rituximab | Drug | 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. |
|
|
| Alemtuzumab | Drug | 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 | Procedure | Infusion of stem cells. |
|
|
| BG001 | Allo MUD & MM | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Allo MUD & MM | 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. |
|
|
| 3 |
| 16 |
| 15 |
| 16 |
| EG001 | Allo MUD & MM | 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. | 2 | 20 | 20 | 20 |
|
| Encephalitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Aspergillus Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Prolonged Hospitalization due to Graft vs Host Disease | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| CMV Pneumonia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Adult Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lower Extremity Edema | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Decreased Left Ventricular Ejection Fraction | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypotension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Atrial Fibrillation | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chest Pain | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chills | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lower GI Bleed | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated Creatinine | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhagic Cystitis | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated Alkaline Phosphatase | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated Alanine Aminotransferase | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated Bilirubin | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Confusion | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headache | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hearing Loss | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| CNS Hemorrhage | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bone Pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Graft versus Host Disease | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infections | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
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| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D008228 | Lymphoma, Non-Hodgkin |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D061067 | Antibodies, Monoclonal, Humanized |