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
4 other identifiers
interventional
5
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1 leukemia
Started Jul 2015
Typical duration for phase_1 leukemia
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 15, 2015
CompletedFirst Posted
Study publicly available on registry
April 22, 2015
CompletedStudy Start
First participant enrolled
July 30, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 6, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
October 6, 2020
CompletedJanuary 8, 2021
January 1, 2021
5.2 years
April 15, 2015
January 6, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.)
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.
100 days after the transplant
Secondary Outcomes (1)
Time to Severe Graft Versus Host Disease (GVHD) or Death
100 days after the transplant
Study Arms (4)
Phase I: Fucosylated T-reg Cells + Chemotherapy
EXPERIMENTALRituximab 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
EXPERIMENTALRituximab 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
EXPERIMENTALRituximab 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
EXPERIMENTALRituximab 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.
Interventions
375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.
40 mg/m2 by vein on Days -8 to -5.
50 mg/kg by vein on Day -8.
2 Gy delivered on Day -4.
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 transplant, MRD, or MUD infused on Day 0.
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
- Cancer Prevention Research Institute of Texascollaborator
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Richard E. Champlin, BS, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 15, 2015
First Posted
April 22, 2015
Study Start
July 30, 2015
Primary Completion
October 6, 2020
Study Completion
October 6, 2020
Last Updated
January 8, 2021
Record last verified: 2021-01