Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Heart and Blood Diseases

Rare Diseases

Leukemia

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Graft vs Host Disease

Hematologic Diseases

Lymphosarcoma

Homologous Wasting Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Busulfan

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Busulfan starting dose of 32 mg/m\^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m\^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.

Starting dose of 32 mg/m\^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3.

Dose of 40 mg/m\^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan.

Dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.

Amin Alousi, MD

The goal of this clinical research study is to learn if cyclophosphamide given after busulfan and fludarabine can help to prevent graft versus host disease (GVHD - a condition in which transplanted tissue attacks the body into which it is transplanted) in patients receiving a stem cell transplant. The safety of this drug combination will also be studied.

The Study Drugs:

Busulfan is designed to bind to DNA (the genetic material of cells), which may cause 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.

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. It is also designed to suppress the immune system and help prevent GVHD.

Study Drug Administration and Transplant:

If you are an inpatient, on Day -8 (8 days before the date of transplant), you will receive a low-level test dose of busulfan through a needle in your vein over 1 hour.

If you are an outpatient, on Day -30 through Day -8, you will receive a low-level test dose of busulfan through a needle in your vein over 1 hour each day.

You will be given an anti-seizure drug to help prevent seizures each time you receive busulfan. Your doctor will explain how the drug will be given and the drug's risks. Seizures are a rare but serious side effect of busulfan.

On Days -8, -6, and -4, blood (about 1 teaspoon each time) will then be drawn a total of 11 times for pharmacokinetic (PK) testing. PK testing measures the amount of study drug 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.

On Day -6 through Day -3, you will receive your body-specific dose of busulfan by vein over 3 hours each day. If you cannot have the blood level tests performed for any reason, you will receive the standard busulfan dose. You will receive fludarabine through a needle in your vein over 1 hour on each of these days before you receive busulfan.

On Day 0, you will receive the donor bone marrow or blood stem cells by vein over about 1 hour.

On Day +3 and Day +4, you will receive cyclophosphamide by vein over 3 hours.

On Days +3 thru +5 just before the first dose of cyclophosphamide and then every 4 hours, you will receive mesna by vein over 30 minutes for a total of 10 doses. Mesna is a drug that protects bladder cells from damage by chemotherapy drugs. It is used to decrease the risk of bleeding in the bladder.

Once a day starting on Day +7, you will receive filgrastim (G-CSF -- a drug that helps with the growth of white blood cells) through a needle under your skin until your blood cell levels reach "recovered" levels for 3 days in a row.

Study Visits:

Every day you are in the hospital and at each outpatient visit, you will have a physical exam to check for symptoms of GVHD.

Blood (about 3 teaspoons) will be drawn at least 2 times a week for the first 100 days after the transplant for routine tests.

About 1 month after your transplant, then once every 3 months up to a year, the following tests and procedures will be performed:

* Blood (about 5 tablespoons) will be drawn for routine tests and to check for CMV. Blood draws may be repeated more often, if you doctor thinks it is needed.
* Urine will be collected for routine tests.
* You will have a bone marrow aspirate and biopsy to check the status of the disease.

At Months 1, 2, 3, 6, and 12 after your transplant, blood (about 4 tablespoons) will be drawn to check the status of your immune system.

Tests and procedures may be repeated more often during the study, if your doctor thinks it is needed.

Length of Study:

You will be on study in the hospital for about 4 weeks. You will be taken off study if the disease gets worse or if the study doctor thinks it is in your best interest.

Long-Term Follow-Up:

After the first 24 months, you will receive either a phone call or a letter from the study doctor or your regular doctor 1 time each year to check the status of the disease. If you are contacted by mail, you will be given a self-addressed stamped envelope with which you can return your responses to the doctor.

This is an investigational study. Busulfan is FDA approved and commercially available for the treatment of chronic myelogenous leukemia (CML). Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Cyclophosphamide is FDA approved and commercially available for the treatment of lymphoma. The use of these drugs together for the possible prevention of GVHD is investigational.

Up to 40 participants will take part in this study. All will be enrolled at M. D. Anderson.

Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide

Busulfan (IV) and Fludarabine Followed by Post-allogeneic Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies.

Graft Versus Host Disease (GVHD) defined as grade 2 to 4 GVHD within first 100 days post transplant. Death or disease progression before diagnosis of GVHD were considered competing risks in the estimation of the incidence of acute GVHD.

Graft Versus Host Disease (GVHD) defined as grade 3 to 4 GVHD within first 100 days post transplant. Death or disease progression before diagnosis of GVHD were considered competing risks in the estimation of the incidence of acute GVHD.

Treatment-Related Mortality (TRM) was estimated from the date of transplant using the cumulative incidence method to account for competing risks. Disease progression or relapse death were considered competing risk for TRM.

Engraftment defined as the evidence of donor derived cells (more than 5%) by bone marrow chimerism studies in the presence of neutrophil recovery by day 28 post stem cell (SC) infusion. Engraftment date is the first day of three (3) consecutive days that the ANC exceeds 0.5 x109/L. Delayed engraftment is defined as the evidence of engraftment beyond day 28 post SC infusion achieved after the administration of therapeutic (high dose) hematopoietic growth factors.

Progression-free survival (PFS) is defined as the interval between day of transplant and day of death or disease progression.

Overall Survival (OS) is defined as the interval between day of transplant and day of death.

M.D. Anderson Cancer Center

Busulfan + Fludarabine + Cyclophosphamide

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Amin M. Alousi, MD/Stem Cell Transplantation

Cumulative Incidence of Grade II to IV Acute GVHD

Cumulative Incidence of Grade III to IV Acute GVHD

Day-100 Treatment-Related Mortality

Rate of Engraftment

2-year Progression-Free Survival

2-year Overall Survival

Overall Study

Symptoms and General Pathology

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Anti-Infective Agents

Rituximab

Sirolimus

Temsirolimus

MTOR Inhibitors

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Anti-Third Party CTL (Cytolytic T-lymphocytes) with Nonmyeloablative SCT (Stem Cell Transplantation)

Rituximab 375 mg/m\^2 intravenously over several hours on Day -13, followed by 1000 mg/m\^2 intravenously on Days -6, 1, and 8; + Cyclophosphamide 50 mg/kg intravenously over two hours on Day -6, immediately following Fludarabine; + Fludarabine 40 mg/m\^2 intravenously over 30 minutes once per day for 4 days, starting Day -6; + Radiation 2Gy Total body radiation day before transplantation + Stem Cell Transplantation + Intravenous infusion of Anti-third Party CTLs.

375 mg/m\^2 intravenously over several hours on Day -13, followed by 1000 mg/m\^2 intravenously on Days -6, 1, and 8.

50 mg/kg intravenously over two hours on Day -6, immediately following Fludarabine.

40 mg/m\^2 intravenously over 30 minutes once per day for 4 days, starting Day -6.

10 mg/kg continuous intravenous infusion for 4 hours for total of 6 doses (24 hours) following Cyclophosphamide.

2Gy Total body radiation day before transplantation

Radiation Treatment

Allo CD34+ Selected SCT/Infusion of stem cells.

Stem Cell Transplantation (SCT)

6 mg by mouth on day -2 followed by 2 mg daily from day -1 through day +7.

Intravenous infusion of anti-third party CTL.

Anti-third Party Cytolytic T-lymphocytes (CTL)

Richard E. Champlin, MD

Primary Objective:

1. To determine the maximally tolerated dose of anti-third party cytolytic T-lymphocytes, defined as the dose which achieve engraftment without severe GVHD (graft-vs-host disease) at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells.

Secondary Objective:

1. Toxicity, response rate, time to progression and overall survival.

GVHD can be a major problem after stem cell transplantation from a healthy donor. It is caused by T-lymphocytes (a type of immune cell) from the donor that can react badly against the person receiving the transplant (the recipient). Researchers want to see if stimulating the donor T-lymphocytes against another person (a third party) and growing them for 28 days will decrease the chance of developing GVHD.

If you are found to be eligible to take part in this study, you will receive the below treatment, including chemotherapy and radiation, before your stem cell transplantation. These include rituximab, cyclophosphamide, fludarabine, and mesna. Rituximab is designed to attach to lymphoma cells, causing them to die. Cyclophosphamide is designed to destroy cancer cells by interfering with their multiplication and slowing or stopping their growth and spread throughout the body. Fludarabine is designed to interfere with DNA repair enzymes so that the leukemic cell cannot repair damaged DNA. This increases the likelihood of the cell dying. Mesna is a drug that lowers the risk of bladder side effects by the cyclophosphamide. Total body radiation is given to to reduce the risk of transplant rejection.

Participants with CLL or lymphoma will receive Rituxan (rituximab) by vein, given over several hours for each dose. The first rituximab dose is 13 days before the transplant. This will be followed by 3 more doses of rituximab, given 6 days before the transplant, and 1 and 8 days after the transplant. All participants will receive fludarabine by vein over 30 minutes once per day for 4 days, starting 6 days before the transplant. All participants will also receive cyclophosphamide by vein over 2 hours. The cyclophosphamide will be given immediately after the first dose of fludarabine. All participants will also receive a continuous infusion of mesna by vein for 24 hours after receiving the cyclophosphamide. One day before transplantation, you will have total body radiation.

After receiving total body radiation, you will receive your stem cell transplantation. On the day of the transplant, you will receive the anti-third party T Lymphocytes (CTLs) by vein. This will be followed by vein infusion of stem cells from the donor. A sample of the anti-third party T-cells cells will also be tested for immune function.

All participants will receive sirolimus by mouth for 10 days, starting 2 days before transplantation. Sirolimus is an immunosuppressive drug which is given to reduce the risk of transplant rejection. You will remain in the hospital for about 4 weeks after the transplant. You will then continue as an outpatient in the Houston area for 100 days after your transplantation, or until your doctor feels it is okay for you to leave the Houston area.

If your disease gets worse after your transplantation, you may receive additional immune cells from the donor (DLI-donor lymphocyte infusion).You may be taken off this study if the transplant does not grow or is rejected, if not enough of the CTLs can be produced, if your disease continues to get worse after receiving additional donors cells, or if you experience any intolerable side effects.

You will have frequent blood tests as medically necessary to evaluate your medical condition. About 3 tablespoons of blood will be collected for immune function testing at 1, 2, 3, 6 and 12 months after the transplant. You will have a bone marrow biopsy, x-rays, and CT scans for evaluation of the cancer at 1, 3, 6, 9, and 12 months after the transplant. The study is over after 1 year. You will be followed-up after that time for routine care, as the doctors feels it is necessary.

This is an investigational study. All of the drugs used in this study, have been approved by the FDA in the treatment of cancer and transplantation. The Miltenyi CliniMACS System which is used to purify stem cells and the anti-third party CTLs has not been approved by the FDA, and its use in this study is experimental. Up to 24 patients will take part in this study. All will be enrolled at M. D. Anderson.

Anti-Third Party T Lymphocytes With Nonmyeloablative Stem Cell Transplantation for Indolent Lymphoid Malignancies

Anti-Third Party T Lymphocytes With Nonmyeloablative Stem Cell Transplantation for Treatment of Indolent Lymphoid Malignancies

Number of participants who achieve engraftment without severe GVHD at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells. Engraftment recorded as first day of three (3) consecutive days that the Absolute neutrophil count (ANC) exceeds 0.5 \* 109/L. Graft failure is defined as failure to reach an ANC \> 0.5 \* 109/L within 28 days after transplantation with detectable donor cells on chimerism analysis.

Maximally tolerated dose of anti-third party cytolytic T-lymphocytes, defined as the dose which achieve engraftment without severe GVHD at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells. Engraftment recorded as first day of three (3) consecutive days that the Absolute neutrophil count (ANC) exceeds 0.5 \* 109/L. For dose-finding, "toxicity" is defined as either death or acute GVHD (aGVHD) within 90 days and "response" is defined as the event the patient is alive and engrafted at day 30.

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Fludarabine phosphate + Cyclophosphamide + Rituximab

25 mg/m\^2 by vein over 5-30 minutes daily for 3 days (days 2-4)

Fludarabine Phosphate

250 mg/m\^2 by vein over 60 minutes daily for 3 days (days 2-4)

375 mg/m\^2 by vein for dose 1 (given 1 day prior to chemotherapy) and then 500 mg/m\^2 on days 2-3

Susan O'Brien, M.D.

Primary Objective:

* To evaluate the efficacy (combined morphologic and flow remissions) of a combination of fludarabine, cyclophosphamide and multiple dose rituximab as frontline therapy for CLL.

Secondary Objective:

* To evaluate remission duration and survival.

DESCRIPTION OF RESEARCH

Fludarabine and cyclophosphamide are chemotherapy drugs that are used in the treatment of CLL. Rituximab is a monoclonal antibody that binds to lymphoma cells and causes cell death.

Before treatment starts, you will have a complete physical exam and routine blood tests (about 2 teaspoons). A bone marrow sample will be collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

Rituximab will be given through a needle (IV) in a vein on Days 1, 2, and 3. One day after the first dose of rituximab (Day 2), fludarabine and cyclophosphamide will be given through a needle (IV) in a vein daily for 3 days (Days 2, 3, 4). After the first month, all the drugs will be given on Days 1, 2, 3. Other IV fluids such as saline will be given on all of the treatment days for hydration, which means that the daily visit will take about six hours. The combination will be repeated once every 4 to 6 weeks for a total of 6 courses.

The drugs acetaminophen (Tylenol) and diphenhydramine hydrochloride (Benadryl) will be given before the dose of rituximab. This will be done to decrease the risk of side effects. If side effects do occur during rituximab treatment, the drug may have to be stopped until the side effects go away and then restarted so the time in the outpatient area may be longer.

The first treatment will be given at M. D. Anderson. The other 5 courses can be performed ether at M. D. Anderson or at home with your regular physician.

The same doses of all three drugs will be used throughout the study unless side effects become severe. In that case, the dose may be lowered or the treatment may be stopped. You will be taken off study if the disease gets worse.

During treatments, patients will have blood samples (about 1 teaspoon each) taken once every 1-2 weeks. Bone marrow studies will be done at the end of the 3rd and 6th chemotherapy courses.

After treatment is completed, you will have blood tests (about 2 teaspoons each) done every 3 months for as long as you are in remission.

This is an investigational study. The FDA has approved all of the drugs used in this study and they are commercially available. However, their use in this study is investigational. As many as 64 patients will take part in the study. All will be enrolled at M. D. Anderson.

Fludarabine, Cyclophosphamide, and Rituximab - High Dose Frontline

Fludarabine, Cyclophosphamide, and Multiple Dose Rituximab as Frontline Therapy in Chronic Lymphocytic Leukemia (CLL)

CR Rate is defined as number of all treated participants with CR as defined by 2008 IWCLL update of NCI-WG response criteria: Complete remission (CR), requiring absence of peripheral blood clonal lymphocytes by immunophenotyping, absence of lymphadenopathy, absence of hepatomegaly or splenomegaly, absence of constitutional symptoms and satisfactory blood counts; Complete remission with incomplete marrow recovery (CRi), defined as CR above, but without normal blood counts; Partial remission (PR), defined as ≥ 50% fall in lymphocyte count, ≥ 50% reduction in lymphadenopathy or ≥ 50% reduction in liver or spleen, together with improvement in peripheral blood counts; Progressive disease (PD): ≥ 50% rise in lymphocyte count to \> 5 x109/L, ≥ 50% increase in lymphadenopathy, ≥ 50% increase in liver or spleen size, Richter's transformation, or new cytopenias due to CLL; Stable disease, defined as not meeting criteria for CR, CRi, PR or PD.

TTP was defined as time from initiation of treatment to primary refractory disease or CLL progression. TTP was censored for therapy-related myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML) and death in remission. TTP calculated using Kaplan-Meier estimates.

OS was defined as the time from the initiation of treatment to last follow-up date or death. OS were calculated using Kaplan-Meier estimates.

Genentech, Inc.

Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response.

Fludarabine phosphate 25 mg/m\^2 intravenous (IV) daily for 3 days (days 2-4) + Cyclophosphamide 250 mg/m\^2 IV daily for 3 days (days 2-4)+ Rituximab 375 mg/m\^2 IV for dose 1 (given 1 day prior to chemotherapy) then 500 mg/m\^2 on days 2-3

FCR-Multiple Dose Rituximab

Susan O'Brien, MD/ Leukemia

Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response. One of the 65 participants was not assessed for response to therapy therefore is not included in analysis. The participant went off study after two months of treatment and was not evaluable for response.

Complete Remission (CR) Rate of FCR3 in Treatment-naïve Participants With Chronic Lymphocytic Leukemia (CLL) at 6 Months

Remission Duration/Time to Progression (TTP)

Of the 66 participants registered, one participant failed screening and therefore was not evaluable for toxicity or response. One of the 65 participants is not included in analysis, the participant went off study after two months of treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide	NCT00800839	Hematologic Dis... Leukemia Lymphoma Myeloma	Busulfan Fludarabine Cyclophosphamid...	6 Months - 75 Years	M.D. Anderson Cancer Center
Anti-Third Party T Lymphocytes With Nonmyeloablative Stem Cell Transplantation for Indolent Lymphoid Malignancies	NCT00473551	Leukemia Lymphoma Myeloma	Rituximab Cyclophosphamid... Fludarabine Mesna Radiation Treat... Stem Cell Trans... Sirolimus Anti-third Part...	18 Years - 70 Years	M.D. Anderson Cancer Center
Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide	NCT00800839	Hematologic Dis... Leukemia Lymphoma Myeloma	Busulfan Fludarabine Cyclophosphamid...	6 Months - 75 Years	M.D. Anderson Cancer Center
Fludarabine, Cyclophosphamide, and Rituximab - High Dose Frontline	NCT00794820	Chronic Lymphoc...	Fludarabine Pho... Cyclophosphamid... Rituximab	16 Years -	M.D. Anderson Cancer Center
Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide	NCT00800839	Hematologic Dis... Leukemia Lymphoma Myeloma	Busulfan Fludarabine Cyclophosphamid...	6 Months - 75 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for neosar®

Every month we try and update this database with for neosar® 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.

Spots Global Cancer Trial Database for neosar®

Every month we try and update this database with for neosar® 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 neosar® 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.