LeukemiaPhase 1NCT02423915
Fucosylated T Cells for Graft Versus Host Disease (GVHD) Prevention
A Phase 1 study testing Rituximab, Fludarabine and Cyclophosphamide in people with Leukemia and Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- What is being tested?
- Rituximab, Fludarabine and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jul 2015to 6 Oct 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with high risk hematologic malignancies, including those with induction failure and in relapse.
- Patients must have matched related or matched unrelated donor source OR CB unit(s) available for the primary transplant which is/are matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The cord(s) must contain at least 3 x 107 total nucleated cells/Kg recipient body weight (pre-thaw).
- Age Criteria: Age >/= 18 and </= 80 years old. Eligibility for pediatric patients will be determined in conjunction with an MDACC pediatrician.
- Bilirubin </= 1.5 mg/dl, SGPT </= 200 IU/ml (unless Gilbert's syndrome).
- Calculated creatinine clearance of >50 mL/min using the Cockcroft-Gault equation for adult patients 18 to 70 years old based on ideal body weight.
- Diffusing capacity for carbon monoxide (DLCO) >/= 45% predicted corrected for hemoglobin. For children </= 7 years of age who unable to perform the pulmonary function test, an O2 saturation of >/= 92% on room air.
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- Left ventricular ejection fraction (LEF) >/= 40%.
- Zubrod performance status </= 2 or Lansky of >/= 60%.
- Twenty-one or more days must have elapsed since the patient's last radiation or chemotherapy administration before beginning treatment for stem cell transplant. Hydrea, Gleevec and other TKI inhibitors as well as intrathecal therapy are accepted exceptions.
- A back-up graft identified, in case of graft failure, from any of the following sources: an available fraction of autologous marrow; or PBPCs harvested and cryopreserved; or family member donor; or a third cord blood unit.
- Able to stop all CYP3A4 inhibitors (voriconazole or posaconazole) at least 7 days before admission.
Who cannot join
- HIV seropositivity.
- Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The PI is the final arbiter of eligibility.
- Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females.
- Unable to sign informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Pilot Study of Infusion of Fucosylated Regulatory T Cells to Prevent Graft Versus Host Disease
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.
Read more
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.
Read the detailed description
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.
- Being tested
- Rituximab, Fludarabine, Cyclophosphamide, Total Body Radiation, Fucosylated Regulatory T Cells
- Keywords
- Leukemia, Lymphoma, Advanced hematologic malignancies, Graft versus host disease, GVHD, Fucosylated umbilical cord blood Regulatory T cells, CB, Tregs, T cells, Cord blood transplant, Total body radiation, TBI, Radiation therapy, XRT, Rituximab, Rituxan, Fludarabine, Fludarabine phosphate, Fludara, Cyclophosphamide
- Medical subject headings
- Leukemia, Lymphoma, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.
FludarabineDrug
Also called Fludarabine Phosphate, Fludara
40 mg/m2 by vein on Days -8 to -5.
CyclophosphamideDrug
Also called Cytoxan, Neosar
50 mg/kg by vein on Day -8.
Total Body RadiationRadiation
Also called Radiation Therapy, XRT, TBI
2 Gy delivered on Day -4.
Fucosylated Regulatory T CellsProcedure or surgery
Also called Tregs
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.
Cord Blood InfusionsProcedure or surgery
Cord blood transplant, MRD, or MUD infused on Day 0.
Also called MMF, CellCept
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.
SirolimusDrug
Also called Rapamune
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 AspirationProcedure or surgery
Bone marrow aspiration performed at 1, 3, 6, and 12 months after transplant to check status of disease.
G-CSFDrug
Also called Filgrastim, Neupogen
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.
Non-Fucosylated Regulatory T CellsProcedure or surgery
Also called Tregs
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.
| Study group | Role | What they receive |
|---|---|---|
| Phase I: Fucosylated T-reg Cells + Chemotherapy | Experimental | 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. Receives: Drug: Rituximab; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Radiation; Procedure: Fucosylated Regulatory T Cells; Procedure: Cord Blood Infusions; Drug: Mycophenolate mofetil; Drug: Sirolimus; Procedure: Bone Marrow Aspiration; Drug: G-CSF |
| Phase I: Non-Fucosylated T-reg Cells + Chemotherapy | Experimental | 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. Receives: Drug: Rituximab; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Radiation; Procedure: Cord Blood Infusions; Drug: Mycophenolate mofetil; Drug: Sirolimus; Procedure: Bone Marrow Aspiration; Drug: G-CSF; Procedure: Non-Fucosylated Regulatory T Cells |
| Phase II: Fucosylated T-reg Cells + Chemotherapy | Experimental | 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. Receives: Drug: Rituximab; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Radiation; Procedure: Fucosylated Regulatory T Cells; Procedure: Cord Blood Infusions; Drug: Mycophenolate mofetil; Drug: Sirolimus; Procedure: Bone Marrow Aspiration; Drug: G-CSF |
| Phase II: Non-Fucosylated T-reg Cells + Chemotherapy | Experimental | 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. Receives: Drug: Rituximab; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Radiation; Procedure: Cord Blood Infusions; Drug: Mycophenolate mofetil; Drug: Sirolimus; Procedure: Bone Marrow Aspiration; Drug: G-CSF; Procedure: Non-Fucosylated Regulatory T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severe Infusional Toxicity
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.)
Measured: 100 days after the transplant
Safety of Administering Fucosylated Umbilical Cord Blood (CB) Regulatory T cells (Tregs) in a CBT, MRD, or MUD Transplant
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.
Measured: 100 days after the transplant
Secondary outcomes (1)
Time to Severe Graft Versus Host Disease (GVHD) or Death
GVHD or death within 100 days of stem cell transplant estimated using standard Bayesian methods, and summarized by counts and percentages.
Measured: 100 days after the transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2015 (estimated)
- Study start30 Jul 2015
- Primary completion6 Oct 2020
- Study completion6 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cancer Prevention Research Institute of Texas
- Responsible party
- Sponsor
- Investigators
- Richard E. Champlin, BS, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02423915
- Sponsor's protocol ID
- 2014-0150
- Other IDs
- NCI-2015-00705, 1R44CA192601-01A1, RP160121
- Status last verified
- Jan 2021
- First submitted
- 15 Apr 2015
- Last updated
- 8 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Infusion of Fucosylated Regulatory T Cells to Prevent Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT02423915
- Acronym / sponsor ID
- 2014-0150
- Keywords
- Leukemia, Lymphoma, Advanced hematologic malignancies, Graft versus host disease, GVHD, Fucosylated umbilical cord blood Regulatory T cells, CB, Tregs
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cancer Prevention Research Institute of Texas
- Study start
- 30 Jul 2015 (actual)
- Primary completion
- 6 Oct 2020 (actual)
- Study completion
- 6 Oct 2020 (actual)
- First posted
- 22 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase I: Fucosylated T-reg Cells + Chemotherapy | Experimental | Drug: Rituximab, Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: Total Body Radiation, Procedure: Fucosylated Regulatory T Cells, Procedure: Cord Blood Infusions, Drug: Mycophenolate mofetil, Drug: Sirolimus, Procedure: Bone Marrow Aspiration, Drug: G-CSFRituximab 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. |
| Phase I: Non-Fucosylated T-reg Cells + Chemotherapy | Experimental | Drug: Rituximab, Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: Total Body Radiation, Procedure: Cord Blood Infusions, Drug: Mycophenolate mofetil, Drug: Sirolimus, Procedure: Bone Marrow Aspiration, Drug: G-CSF, Procedure: Non-Fucosylated Regulatory T CellsRituximab 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. |
| Phase II: Fucosylated T-reg Cells + Chemotherapy | Experimental | Drug: Rituximab, Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: Total Body Radiation, Procedure: Fucosylated Regulatory T Cells, Procedure: Cord Blood Infusions, Drug: Mycophenolate mofetil, Drug: Sirolimus, Procedure: Bone Marrow Aspiration, Drug: G-CSFRituximab 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. |
| Phase II: Non-Fucosylated T-reg Cells + Chemotherapy | Experimental | Drug: Rituximab, Drug: Fludarabine, Drug: Cyclophosphamide, Radiation: Total Body Radiation, Procedure: Cord Blood Infusions, Drug: Mycophenolate mofetil, Drug: Sirolimus, Procedure: Bone Marrow Aspiration, Drug: G-CSF, Procedure: Non-Fucosylated Regulatory T CellsRituximab 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with high risk hematologic malignancies, including those with induction failure and in relapse.
- Patients must have matched related or matched unrelated donor source OR CB unit(s) available for the primary transplant which is/are matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. The cord(s) must contain at least 3 x 107 total nucleated cells/Kg recipient body weight (pre-thaw).
- Age Criteria: Age >/= 18 and </= 80 years old. Eligibility for pediatric patients will be determined in conjunction with an MDACC pediatrician.
- Bilirubin </= 1.5 mg/dl, SGPT </= 200 IU/ml (unless Gilbert's syndrome).
- Calculated creatinine clearance of >50 mL/min using the Cockcroft-Gault equation for adult patients 18 to 70 years old based on ideal body weight.
Key exclusion criteria (4 listed)
- HIV seropositivity.
- Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The PI is the final arbiter of eligibility.
- Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females.
- Unable to sign informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: Rituxan375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies. | Drug | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
| FludarabineAlso: Fludarabine Phosphate, Fludara40 mg/m2 by vein on Days -8 to -5. | Drug | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
| CyclophosphamideAlso: Cytoxan, Neosar50 mg/kg by vein on Day -8. | Drug | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
| Total Body RadiationAlso: Radiation Therapy, XRT, TBI2 Gy delivered on Day -4. | Radiation | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
| Fucosylated Regulatory T CellsAlso: TregsPhase 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. | Procedure or surgery | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy |
| Cord Blood InfusionsCord blood transplant, MRD, or MUD infused on Day 0. | Procedure or surgery | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
| Mycophenolate mofetilAlso: MMF, CellCept15 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. | Drug | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
| SirolimusAlso: Rapamune12 mg by mouth load followed by 4 mg by mouth daily from Day -3 to Day +180 in the absence of GVHD. | Drug | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
| Bone Marrow AspirationBone marrow aspiration performed at 1, 3, 6, and 12 months after transplant to check status of disease. | Procedure or surgery | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
| G-CSFAlso: Filgrastim, Neupogen5 mcg/kg/day subcutaneously beginning on D+0, and continuing until absolute neutrophil count (ANC) is > 500 x 10/L for 3 consecutive days. | Drug | Phase I: Fucosylated T-reg Cells + Chemotherapy, Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
| Non-Fucosylated Regulatory T CellsAlso: TregsPhase 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. | Procedure or surgery | Phase I: Non-Fucosylated T-reg Cells + Chemotherapy, Phase II: Non-Fucosylated T-reg Cells + Chemotherapy |
Primary outcome
Severe Infusional Toxicity
Time frame: 100 days after the transplant
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.)
Safety of Administering Fucosylated Umbilical Cord Blood (CB) Regulatory T cells (Tregs) in a CBT, MRD, or MUD Transplant
Time frame: 100 days after the transplant
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.
1 secondary outcome
Time to Severe Graft Versus Host Disease (GVHD) or Death
Time frame: 100 days after the transplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2021.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard E. Champlin, BS, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rituximab, Fludarabine and Cyclophosphamide in people with Leukemia and Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severe Infusional Toxicity (time frame: 100 days after the transplant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2021.