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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02423915
Recruitment Status : Active, not recruiting
First Posted : April 22, 2015
Last Update Posted : May 10, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Cancer Prevention Research Institute of Texas
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.


Condition or disease Intervention/treatment Phase
Leukemia Lymphoma 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 Procedure: Non-Fucosylated Regulatory T Cells Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of Infusion of Fucosylated Regulatory T Cells to Prevent Graft Versus Host Disease
Actual Study Start Date : July 30, 2015
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

Drug: Rituximab
375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.
Other Name: Rituxan

Drug: Fludarabine
40 mg/m2 by vein on Days -8 to -5.
Other Names:
  • Fludarabine Phosphate
  • Fludara

Drug: Cyclophosphamide
50 mg/kg by vein on Day -8.
Other Names:
  • Cytoxan
  • Neosar

Radiation: Total Body Radiation
2 Gy delivered on Day -4.
Other Names:
  • Radiation Therapy
  • XRT
  • TBI

Procedure: Fucosylated Regulatory T Cells

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.

Other Name: Tregs

Procedure: Cord Blood Infusions
Cord blood transplant, MRD, or MUD infused on Day 0.

Drug: Mycophenolate mofetil
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.
Other Names:
  • MMF
  • CellCept

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

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

Drug: G-CSF
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.
Other Names:
  • Filgrastim
  • Neupogen

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.

Drug: Rituximab
375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.
Other Name: Rituxan

Drug: Fludarabine
40 mg/m2 by vein on Days -8 to -5.
Other Names:
  • Fludarabine Phosphate
  • Fludara

Drug: Cyclophosphamide
50 mg/kg by vein on Day -8.
Other Names:
  • Cytoxan
  • Neosar

Radiation: Total Body Radiation
2 Gy delivered on Day -4.
Other Names:
  • Radiation Therapy
  • XRT
  • TBI

Procedure: Cord Blood Infusions
Cord blood transplant, MRD, or MUD infused on Day 0.

Drug: Mycophenolate mofetil
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.
Other Names:
  • MMF
  • CellCept

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

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

Drug: G-CSF
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.
Other Names:
  • Filgrastim
  • Neupogen

Procedure: Non-Fucosylated Regulatory T Cells

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.

Other Name: Tregs

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.

Drug: Rituximab
375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.
Other Name: Rituxan

Drug: Fludarabine
40 mg/m2 by vein on Days -8 to -5.
Other Names:
  • Fludarabine Phosphate
  • Fludara

Drug: Cyclophosphamide
50 mg/kg by vein on Day -8.
Other Names:
  • Cytoxan
  • Neosar

Radiation: Total Body Radiation
2 Gy delivered on Day -4.
Other Names:
  • Radiation Therapy
  • XRT
  • TBI

Procedure: Fucosylated Regulatory T Cells

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.

Other Name: Tregs

Procedure: Cord Blood Infusions
Cord blood transplant, MRD, or MUD infused on Day 0.

Drug: Mycophenolate mofetil
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.
Other Names:
  • MMF
  • CellCept

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

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

Drug: G-CSF
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.
Other Names:
  • Filgrastim
  • Neupogen

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.

Drug: Rituximab
375 mg/m2 by vein on Day -12 for for participants with CD20+ malignancies.
Other Name: Rituxan

Drug: Fludarabine
40 mg/m2 by vein on Days -8 to -5.
Other Names:
  • Fludarabine Phosphate
  • Fludara

Drug: Cyclophosphamide
50 mg/kg by vein on Day -8.
Other Names:
  • Cytoxan
  • Neosar

Radiation: Total Body Radiation
2 Gy delivered on Day -4.
Other Names:
  • Radiation Therapy
  • XRT
  • TBI

Procedure: Cord Blood Infusions
Cord blood transplant, MRD, or MUD infused on Day 0.

Drug: Mycophenolate mofetil
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.
Other Names:
  • MMF
  • CellCept

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

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

Drug: G-CSF
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.
Other Names:
  • Filgrastim
  • Neupogen

Procedure: Non-Fucosylated Regulatory T Cells

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.

Other Name: Tregs




Primary Outcome Measures :
  1. 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.)

  2. 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.


Secondary Outcome Measures :
  1. Time to Severe Graft Versus Host Disease (GVHD) or Death [ Time Frame: 100 days after the transplant ]
    GVHD or death within 100 days of stem cell transplant estimated using standard Bayesian methods, and summarized by counts and percentages.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 >/= 16 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, and the Schwartz equation for pediatric patients 6 months to 17 years old.
  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.
  12. Patient or patient's legal representative, parent(s) or guardian able to sign informed consent. Age 7-18 able to provide assent.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02423915


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Cancer Prevention Research Institute of Texas
Investigators
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Principal Investigator: Borje S. Andersson, MD, PHD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02423915     History of Changes
Other Study ID Numbers: 2014-0150
NCI-2015-00705 ( Registry Identifier: NCI CTRP )
1R44CA192601-01A1 ( U.S. NIH Grant/Contract )
RP160121 ( Other Grant/Funding Number: The Cancer Prevention and Research Institute of Texas (CPRIT) )
First Posted: April 22, 2015    Key Record Dates
Last Update Posted: May 10, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
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
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Vidarabine
Sirolimus
Mycophenolic Acid
Cyclophosphamide
Rituximab
Fludarabine
Fludarabine phosphate
Everolimus
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Anti-Bacterial Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antibiotics, Antitubercular
Antitubercular Agents