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

Part of paid clinical trials in Houston, Texas.

Sponsor
M.D. Anderson Cancer Center
Study ID
NCT02423915
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Rituximab — DRUG
    375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.
  • Fludarabine — DRUG
    40 mg/m2 by vein on Days -8 to -5.
  • Cyclophosphamide — DRUG
    50 mg/kg by vein on Day -8.
  • Total Body Radiation — RADIATION
    2 Gy delivered on Day -4.
  • Fucosylated Regulatory T Cells — PROCEDURE
    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 Infusions — PROCEDURE
    Cord blood transplant, MRD, or MUD infused on Day 0.
  • Mycophenolate mofetil — DRUG
    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 — DRUG
    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 — PROCEDURE
    Bone marrow aspiration performed at 1, 3, 6, and 12 months after transplant to check status of disease.
  • G-CSF — DRUG
    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 Cells — PROCEDURE
    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 Details

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.

Key Dates

Start date
Jul 30, 2015
Status verified
Jan 2021
Primary completion
Oct 6, 2020
Completion
Oct 6, 2020

Study Design

Enrollment
5 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase I: Fucosylated T-reg Cells + Chemotherapy
    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.
  • Experimental: Phase I: Non-Fucosylated T-reg Cells + Chemotherapy
    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.
  • Experimental: Phase II: Fucosylated T-reg Cells + Chemotherapy
    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.
  • Experimental: Phase II: Non-Fucosylated T-reg Cells + Chemotherapy
    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.

Primary Outcome Measure

Severe Infusional Toxicity [ Time Frame: 100 days after the transplant ]

Locations (1)

FacilityCityStateZIPSite coordinators
University of Texas MD Anderson Cancer CenterHoustonTexas77030-

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