Clinical trial · Interventional

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

NCT02423915CI-TRIAL-00049329completedPhase 1ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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.

Conditions

Conditions (2)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Leukemia	Leukemia	ONTOLOGY_EXACT	0.90
Lymphoma	Lymphoma	ONTOLOGY_EXACT	0.90

Interventions

Interventions (11)

Intervention	Type	Mapped drug	Match
Bone Marrow Aspiration	Procedure	—	UNRESOLVED
Cord Blood Infusions	Procedure	—	UNRESOLVED
Cyclophosphamide	Drug	Cyclophosphamide	ALIAS
Fludarabine	Drug	Fludarabine	ALIAS
Fucosylated Regulatory T Cells	Procedure	—	UNRESOLVED
G-CSF	Drug	—	UNRESOLVED
Mycophenolate mofetil	Drug	—	UNRESOLVED
Non-Fucosylated Regulatory T Cells	Procedure	—	UNRESOLVED
Rituximab

Design

Arms and outcomes

Arms (4)

type
EXPERIMENTAL
label
Phase I: Fucosylated T-reg Cells + Chemotherapy
description
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.
interventionNames
1. Drug: Rituximab
2. Drug: Fludarabine
3. Drug: Cyclophosphamide
4. Radiation: Total Body Radiation
5. Procedure: Fucosylated Regulatory T Cells
6. Procedure: Cord Blood Infusions
7. Drug: Mycophenolate mofetil
8. Drug: Sirolimus
9. Procedure: Bone Marrow Aspiration
10. Drug: G-CSF

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 80 Years

Show eligibility criteria text

Inclusion Criteria:

1. Patients with high risk hematologic malignancies, including those with induction failure and in relapse.
2. 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).
3. Age Criteria: Age \>/= 18 and \</= 80 years old. Eligibility for pediatric patients will be determined in conjunction with an MDACC pediatrician.
4. Bilirubin \</= 1.5 mg/dl, SGPT \</= 200 IU/ml (unless Gilbert's syndrome).
5. 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.
6. 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.
7. Left ventricular ejection fraction (LEF) \>/= 40%.
8. Zubrod performance status \</= 2 or Lansky of \>/= 60%.
9. 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.
10. 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.
11. Able to stop all CYP3A4 inhibitors (voriconazole or posaconazole) at least 7 days before admission.

Exclusion Criteria:

1. HIV seropositivity.
2. Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The PI is the final arbiter of eligibility.
3. 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.
4. Unable to sign informed consent.

References

Publications (0)

Data not yet available

No reference posted for this study.

Registry

Dates and enrollment

Start: Jul 30, 2015
Primary completion: Oct 6, 2020
Completion: Oct 6, 2020
First posted: Apr 22, 2015
Last update posted: Jan 8, 2021
Enrollment: 5 (actual)
Lead sponsor: M.D. Anderson Cancer Center OTHER
Collaborators: National Cancer Institute (NCI); Cancer Prevention Research Institute of Texas
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, Cytoxan, Neosar, Mycophenolate, Mycophenolate mofetil, MMF, CellCept, Sirolimus, Rapamune, G-CSF, Filgrastim, Neupogen

Data updated 22 days agoSource updated Jan 8, 2021source: clinicaltrials

Locations

Locations by country (1)

Country	Sites	Recruiting
United States	1