Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Lymphoma

Hematologic Neoplasms

Graft vs Host Disease

Lymphosarcoma

Homologous Wasting Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Rituximab

Lenograstim

Mycophenolic Acid

Sirolimus

Temsirolimus

MTOR Inhibitors

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Rituximab 375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.

Fludarabine 40 mg/m2 by vein on Days -8 to -5.

Cyclophosphamide 50 mg/kg by vein on Day -8.

Mesna administered on Day -8 immediately following completion of the Fludarabine.

Total body radiation 2 Gy delivered on Day -4.

3rd party CB Treg infusion on Day -1.

Three (3) participants treated at cell dose level 1: 1 x 10\^6/kg fucosylated T-reg cells. The cells are infused on Day -1.

Cord blood transplant, MRD, or MUD transplant on Day 0.

Mycophenolate 15 mg/kg by vein or mouth from Day -3 to Day +100 in the absence of GVHD.

Sirolimus 12 mg by mouth load followed by 4 mg by mouth daily from Day -3 to Day +180 in the absence of GVHD.

G-CSF 5 mcg/kg/day subcutaneously beginning on D+0 for CORD blood stem cell transplant and D+7 for allogeneic stem cell transplant, and continuing until the absolute neutrophil count (ANC) is \> 500 x 10/L for 3 consecutive days.

Rituximab 375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.

Fludarabine 40 mg/m2 by vein on Days -8 to -5.

Cyclophosphamide 50 mg/kg by vein on Day -8.

Total body radiation 2 Gy delivered on Day -4.

3rd party CB Treg infusion on Day -1.

Ten (10) participants treated with non-fucosylated T-reg cells at dose level 2: 1 x 10\^7/kg T-reg cells. The cells are infused on Day -1.

Cord blood transplant, MRD, or MUD infused on Day 0.

Mycophenolate 15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or mouth from Day -3 to Day +100 in the absence of GVHD.

Sirolimus 12 mg by mouth load followed by 4 mg by mouth daily from Day -3 to Day +180 in the absence of GVHD.

G-CSF 5 mcg/kg/day subcutaneously beginning on D+0 for CORD blood stem cell transplant and D+7 for allogeneic stem cell transplant, and continuing until the absolute neutrophil count (ANC) is \> 500 x 10/L for 3 consecutive days.

Rituximab 375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.

Fludarabine 40 mg/m2 by vein on Days -8 to -5.

Cyclophosphamide 50 mg/kg by vein on Day -8.

Total body radiation 2 Gy delivered on Day -4.

Seventeen (17) participants treated with Fucosylated T-reg cells at dose level 2: 1 x 10\^7/kg. The cells are infused on Day -1.

Cord blood transplant, MRD, or MUD infused on Day 0.

Mycophenolate 15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or mouth from Day -3 to Day +100 in the absence of GVHD.

Sirolimus 12 mg by mouth load followed by 4 mg by mouth daily from Day -3 to Day +180 in the absence of GVHD.

G-CSF 5 mcg/kg/day subcutaneously beginning on D+0 for CORD blood stem cell transplant and D+7 for allogeneic stem cell transplant, and continuing until the absolute neutrophil count (ANC) is \> 500 x 10/L for 3 consecutive days.

Rituximab 375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.

Fludarabine 40 mg/m2 by vein on Days -8 to -5.

Cyclophosphamide 50 mg/kg by vein on Day -8.

Total body radiation 2 Gy delivered on Day -4.

Seventeen (17) participants treated with Non-Fucosylated T-reg cells at dose level 2: 1 x 10\^7/kg. The cells are infused on Day -1.

Cord blood transplant, MRD, or MUD infused on Day 0.

Mycophenolate 15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or mouth from Day -3 to Day +100 in the absence of GVHD.

Sirolimus 12 mg by mouth load followed by 4 mg by mouth daily from Day -3 to Day +180 in the absence of GVHD.

G-CSF 5 mcg/kg/day subcutaneously beginning on D+0 for CORD blood stem cell transplant and D+7 for allogeneic stem cell transplant, and continuing until the absolute neutrophil count (ANC) is \> 500 x 10/L for 3 consecutive days.

375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.

Total Body Radiation

Phase I: Participants treated at cell dose level 1: 1 x 10\^6/kg Fucosylated T-reg cells on Day -1.

Phase II: Participants treated at cell dose level 2: 1 x 10\^7/kg Fucosylated T-reg cells on Day -1.

Fucosylated Regulatory T Cells

Cord blood transplant, MRD, or MUD infused on Day 0.

Cord Blood Infusions

15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or mouth from Day -3 to Day +100 in the absence of GVHD.

Mycophenolate mofetil

12 mg by mouth load followed by 4 mg by mouth daily from Day -3 to Day +180 in the absence of GVHD.

Bone marrow aspiration performed at 1, 3, 6, and 12 months after transplant to check status of disease.

Bone Marrow Aspiration

5 mcg/kg/day subcutaneously beginning on D+0, and continuing until absolute neutrophil count (ANC) is \> 500 x 10/L for 3 consecutive days.

G-CSF

Phase I: Participants treated at cell dose level 1: 1 x 10\^7/kg Non-Fucosylated T-reg cells on Day -1.

Phase II: Participants treated at cell dose level 2: 1 x 10\^7/kg Non-Fucosylated T-reg cells on Day -1.

Non-Fucosylated Regulatory T Cells

Richard E. Champlin, BS, MD

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

T-cells are white blood cells that are important to the immune system. The T cells for this study (called regulatory T-cells, or Tregs) will be from a donor who is not related to you. Before the Tregs are given to you, they may be changed in the laboratory to make use of sugar that is found in small amounts in blood cells through a process called fucosylation. They are then called fucosylated Tregs. Adding more sugars to the Tregs in the laboratory is designed to help the Tregs find their way faster to the bone marrow, which may help low blood counts to recover faster.

The goal of this clinical research study is to learn if it is safe and practical to give fucosylated Tregs to patients who will receive a matched related donor (MRD), a matched unrelated donor (MUD), or cord blood transplant. Researchers also want to learn if these Tregs may prevent or reduce the effects of graft-versus host disease (GVHD). GVHD can result from a reaction of the transplanted cord blood cells against certain tissues in the body.

This is an investigational study. Fucosylation of Tregs is not an FDA-approved process. It is currently being used for research purposes only. Fludarabine, melphalan, cyclophosphamide and rituximab are FDA approved and commercially available to be given to patients with leukemia or lymphoma having a cord blood transplant. Total body irradiation is delivered using FDA-approved and commercially available methods.

Up to 47 patients will take part in this study. All will be enrolled at MD Anderson.

Central Venous Catheter Placement:

You will first have a central venous catheter (CVC) placed. 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 it.

The chemotherapy, some of the other drugs in this study, the Tregs, and the MRD, MUD or cord blood transplant will be given by vein through your CVC. Some blood samples will also be drawn through your CVC. The CVC will remain in your body for about 2-5 months.

Study Treatments:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of Tregs based on when you joined this study. You may receive fucosylated or non-fucosylated Treg cells. Two dose levels of fucosylated Tregs will be tested. Up to 3 participants will be enrolled in Dose Level 1, and up to 17 will be in Dose Level 2. The first group of participants will receive the lower dose level. The next group will receive a higher dose than the first group, if no intolerable side effects were seen.

The next 10 participants will receive non-fucosylated Tregs at Dose Level 2.

The last 34 patients enrolled in the study will be will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups and will have an equal chance of receiving either fucosylated or non-fucosylated Treg cells.

You will receive 1 of 2 preparative regimens before your transplant. These regimens are used to prepare your body to receive the transplant. Your study doctor will decide which regimen is best for you.

Regimen #1:

On Day -12, you will receive rituximab by vein over 4-6 hours, if you are receiving it. This will depend on the disease that you have.

On Day -9, you will be admitted to the hospital and given fluids by vein to hydrate you.

On Day -8, you will receive fludarabine and cyclophosphamide by vein over 1 hour. You will also receive mesna by vein over 30-60 minutes before the cyclophosphamide dose and then every 4 hours for a total of 5 doses. Mesna is given to lower the risk of side effects to the bladder caused by cyclophosphamide.

On Days -7, -6, and -5, you will receive fludarabine by vein over 1 hour.

On Day -4, you will receive a single treatment of low-dose total body irradiation as part of the standard of care for stem cell transplants. You will receive a separate consent form that describes this procedure and its risks.

On Day -1, you will receive the Tregs by vein over 30-60 minutes.

On Day 0, you will receive your stem cell transplant through the CVC over about 30 minutes to several hours depending on the donor type of stem cell transplant you receive.

Regimen #2:

On Day -12, you will receive rituximab by vein over 4-6 hours, if you are receiving it. This will depend on the disease that you have.

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

On Days -5, -4, -3 and -2, you will receive fludarabine by vein over 1 hour.

On Day -2, you will receive melphalan by vein over 30 mins.

On Day -1, you will receive the Tregs by vein over 30-60 minutes.

On Day 0, you will receive your stem cell transplant through the CVC over about 30 minutes to several hours depending on the donor type of stem cell transplant you receive.

Supportive Drugs:

You will be given standard drugs to help decrease the risk of side effects. You may ask the study staff about how the drugs are given and their risks.

Starting on Day -3, you will receive sirolimus by mouth once a day. You will receive mycophenolate mofetil (MMF) as a tablet by mouth 3 times a day.

If you are not able to take the MMF tablet by mouth, you will receive MMF by vein over 2 hours. If you do not have GVHD at Day 100, the dose of MMF will be gradually lowered. If you have GVHD, MMF may be stopped 7 days after the GVHD is controlled. If you do not have GVHD at Day 180 after your transplant, the dose of sirolimus will be gradually lowered. Your doctor will discuss this with you.

You will receive filgrastim as an injection under the skin 1 time a day, starting on Day 0 for cord blood transplant or Day 7 for a matched related or MUD transplant, until your blood cell levels return to normal. Filgrastim is designed to help with the growth of white blood cells.

Study Visits:

As part of standard care, you will remain in the hospital for about 4 weeks after the transplant. After you are released from the hospital, you will continue as an outpatient in the Houston area to be monitored for infections and transplant-related complications.

On Days -10, -1, 0, +1, +3, +7, +14, +21, and then at 1, 2, 3, 6, and 12 months after the transplant, blood (about 3 tablespoons) will be drawn to check your immune function, response to the T cells, inflammatory responses, and for GVHD markers. If possible, the blood will be collected during standard of care blood draws so that no additional needle sticks will be needed.

About 1, 3, 6, and 12 months after the transplant:

* You will have a physical exam.
* You will be checked for possible reactions to the transplant and study drugs, including GVHD.
* Blood (about 4 teaspoons) will be drawn for routine tests, to check for cytomegalovirus (CMV), and for genetic tests to learn if your body has accepted the donor cells.

Urine will be collected for routine tests.

* If the doctor thinks it is needed, you will have a bone marrow aspiration to check the status of the disease. To collect a bone marrow aspiration/biopsy, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.
* If you have lymphoma or Hodgkin's Disease and the doctor thinks it is needed, you will have a CT scan of your neck, chest, abdomen, and pelvis to check the status of the disease.

Length of Study:

You will be on study for up to 1 year. You will be taken off study early if the disease gets worse, if intolerable side effects occur, if not enough T cells can be created, if you are unable to follow study directions, or if your doctor thinks it is in your best interest.

Fucosylated T Cells for Graft Versus Host Disease (GVHD) Prevention

Pilot Study of Infusion of Fucosylated Regulatory T Cells to Prevent Graft Versus Host Disease

Severe infusional toxicity defined according to NCI CTCAE v4.0 (Prolonged (ie, not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae. Life-threatening consequences; urgent intervention indicated.)

For the purpose of safety monitoring, "failure" defined as F100 = \[T \< 100 days\]. The Bayesian method of Thall, et al.42 used for safety monitoring.

GVHD or death within 100 days of stem cell transplant estimated using standard Bayesian methods, and summarized by counts and percentages.

National Cancer Institute (NCI)

Cancer Prevention Research Institute of Texas

M.D. Anderson Cancer Center

Heart and Blood Diseases

Symptoms and General Pathology

Multiple Myeloma

Neoplasms, Plasma Cell

Leukemia, Lymphoid

Anemia

Anemia, Aplastic

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Lymphocytic, Chronic, B-Cell

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Chronic Graft Versus Host Disease

Aplastic Anemia

Acute Non Lymphoblastic Leukemia

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Melphalan

Cord Blood

Zachariah DeFilipp, MD

This trial will use two cord blood units for transplantation using a reduced intensity regimen rather than using intense doses of chemotherapy and radiation therapy. Two cord blood units (double cord blood) are being used, as the numbers of blood cells in one unit are too few to allow successful growth of these cells.

Because the risk of infection, particularly virus infection, is high after double cord blood transplant, this study seeks to reduce the rise of virus infection by using a reduced intensity regimen without a medicine called antithymocyte globulin (ATG), as used in prior cord blood transplants. Subjects will receive two chemotherapy drugs, melphalan and fludarabine, and low dose of total body radiation (one treatment) instead of the ATG. The number of patients with virus infections in this study will be compared to our prior experience using the ATG.

Subjects will receive their transplants as in-patients.

* IV-Catheter

  * one or two IV catheters will be placed on the day of hospital admission
* Conditioning

  * Fludarabine IV six days before transplant (days -7, -6, -5. -4, -3, -2)
  * Melphalan IV (day -1)
  * Total body radiation on day 0 (same day as transplant)
* Immunosuppressive Therapy

  * Tacrolimus and sirolimus beginning day -3, daily for 6-9 months post-transplant. Given IV as in-patient, orally as out-patient
* Infusion of Cord Blood units

  * 2 cord blood units IV on Day 0 Routine post-transplant supportive care will be provided

Reduced Intensity Double Umbilical Cord Blood Transplantation

A Phase II Study of Reduced Intensity Double Umbilical Cord Blood Transplantation Using Fludarabine, Melphalan, and Low Dose Total Body Radiation

The one year significant infection rate (infections requiring medical intervention) after double umbilical cord blood transplant using a novel conditioning regimen of fludarabine/melphalan/low dose total body radiation. The data is shown as the number of significant infections participants experienced during the first year, measured from the start of treatment.

The median number of days measured from the time of transplantation, until the first documented neutrophil engraftment. neutrophil engraftment is defined as the first of 3 consecutive days of absolute neutrophil count \> 500 neutrophils per microliter of blood.

The time to platelet engraftment is measured from the time of transplantation until the time of first documented platelet engraftment. Platelet engraftment is defined as a platelet count ≥ 20,000/µL for three consecutive measurements over three or more days. The first of the three days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 3 days or in the following 7 days after the day of engraftment, unless the platelet transfusion is being given specifically to achieve a platelet threshold to allow an elective invasive procedure, such as a central catheter removal.

Primary graft failure is defined as the failure to achieve an absolute neutrophil count (ANC) \>500/ µL by day 42, in the absence of relapse.

Acute GVHD is assessed using Consensus Criteria:

Organ Classifications:

* 0: No rash due to GVHD; Bilirubin \< 2 mg/dL; \< 500 mL diarrhea/ day
* 1: Maculopapular rash \< 25% of body surface; Bilirubin 2-3 mg/dL; 500 to 999 mL diarrhea/ day or persistent nausea with histologic evidence of GVHD in stomach/ duodenum
* 2: Maculopapular rash 25-50% of body surface; Bilirubin 3.1-6 mg/dL; 1,000 to 1,499 mL diarrhea/ day
* 3: Maculopapular rash \> 50% of body surface; Bilirubin 6.1-15 mg/dL; 1,500 or more mL diarrhea/ day
* 4: Generalized erythroderma with bullous formation; Bilirubin \> 15 mg/dL; Severe abdominal pain with or without ileus

Overall Clinical Grade:

* 0: No Stage 1-4 of any organ
* I: Stage 1-2 rash and no liver or gut involvement
* II: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 gut involvement
* III: None to Stage 3 skin rash with Stage 2-3 liver involvement, or Stage 2-4 gut involvement
* IV: Stage 4 skin rash, or Stage 4 liver involvement

Chronic Graft Versus Host Disease (GVHD) is assessed using the National Institutes of Health (NIH) consensus criteria.

The percentage of treatment related participant deaths within 100 days of receiving umbilical cord blood transplantation. All deaths in the absence of relapse of the primary malignancy will be considered treatment related mortality.

The percentage of participants that have not died or had disease progression by two years. Relapse is defined by either morphological or cytogenetic evidence of the original malignancy consistent with pre-transplant features.

The percentage of participants alive at two years

The percentage of participants that relapsed within 12 months. Relapse is defined by either morphological or cytogenetic evidence of the original malignancy consistent with pre-transplant features.

The number of participants that were found to have lymphoma post-transplant.

Massachusetts General Hospital

Hematology/Oncology

The two participants found to be ineligible after being consented and registered were excluded from the analysis.

All patients receive same therapy

Fludarabine: 30 mg/m2/day IV x 6 days

Melphalan: 100 mg/m2/day IV x 1 day

Total Body Radiation: 200 cGy on Day 0

Cord Blood: 2 cord blood units IV

Fludarabine/Melphalan/TBI

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

Eastern Cooperative Oncology Group (ECOG) Performance Status:

* 0 - Asymptomatic (Fully active, able to carry on all predisease activities without restriction)
* 1 - Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work)
* 2 - Symptomatic, \<50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours)

Performance Status

Disease

Dr. Zachariah DeFilipp

Number of Participants With a Clinically Significant Infection

The two participants found to be ineligible after being consented and registered were excluded from the analysis. In addition to those two participants, the 8 participants that did not achieve engraftment were not included in the analysis.

Median Time to Neutrophil Engraftment

The two participants found to be ineligible after being consented and registered were excluded from the analysis. In addition to those two participants, the 10 participants that did not achieve engraftment were not included in the analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fucosylated T Cells for Graft Versus Host Disease (GVHD) Prevention	NCT02423915	Leukemia Lymphoma	Rituximab Fludarabine Cyclophosphamid... Total Body Radi... Fucosylated Reg... Cord Blood Infu... Mycophenolate m... Sirolimus Bone Marrow Asp... G-CSF Non-Fucosylated...	18 Years - 80 Years	M.D. Anderson Cancer Center
Fucosylated T Cells for Graft Versus Host Disease (GVHD) Prevention	NCT02423915	Leukemia Lymphoma	Rituximab Fludarabine Cyclophosphamid... Total Body Radi... Fucosylated Reg... Cord Blood Infu... Mycophenolate m... Sirolimus Bone Marrow Asp... G-CSF Non-Fucosylated...	18 Years - 80 Years	M.D. Anderson Cancer Center
Reduced Intensity Double Umbilical Cord Blood Transplantation	NCT01408563	Non-Hodgkin's L... Hodgkin's Lymph... Multiple Myelom... Chronic Lymphoc... Acute Myelogeno...	Fludarabine Melphalan Total Body Radi... Cord Blood	18 Years - 70 Years	Massachusetts General Hospital
Reduced Intensity Double Umbilical Cord Blood Transplantation	NCT01408563	Non-Hodgkin's L... Hodgkin's Lymph... Multiple Myelom... Chronic Lymphoc... Acute Myelogeno...	Fludarabine Melphalan Total Body Radi... Cord Blood	18 Years - 70 Years	Massachusetts General Hospital

Spots Global Cancer Trial Database for total body radiation