NCT02118311

Brief Summary

This is a Simon's optimal two-stage phase II trial designed to estimate grade II-IV acute graft-versus-host disease (GVHD) after infusion of T regulatory (nTreg) in a fixed dose ratio to the combined CD3+ cell count of the two graft units in recipients of double UCB transplantation. The nTreg cells (manufactured from a 3rd cord blood unit) are infused on day 0 at least 1 hour after the 2nd unit of the double umbilical cord blood (UCB) transplant. The nTreg cells require an 18 day (±2 days) lead time based on the planned transplant day. The combined CD3+ cell content from the two graft UCB units is enumerated upon thaw (day 0). The patient then receives the number of nTregs cells from the 3rd cord product to achieve a Treg:CD3+ cells ratio of 5:1. The nTreg cell dose depends on the CD3+ cell content of the two graft UCB graft units, but it will not exceed the highest dose level safely tested in the ongoing University of Minnesota phase I Treg dose escalation study MT 2006-01.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Jun 2016

Geographic Reach
1 country

1 active site

Status
withdrawn

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

March 26, 2014

Completed
26 days until next milestone

First Posted

Study publicly available on registry

April 21, 2014

Completed
2.1 years until next milestone

Study Start

First participant enrolled

June 1, 2016

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2018

Completed
Last Updated

December 2, 2017

Status Verified

November 1, 2017

Enrollment Period

2.3 years

First QC Date

March 26, 2014

Last Update Submit

November 29, 2017

Conditions

Hematologic Malignancies

Keywords

Acute LeukemiasBurkitt's LymphomaNatural Killer Cell MalignanciesChronic Myelogenous LeukemiaMyelodysplastic SyndromeLarge-Cell LymphomaHodgkin LymphomaMultiple MyelomaChronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaMarginal Zone B-Cell LymphomaFollicular Lymphoma:Lymphoplasmacytic LymphomaMantle-Cell LymphomaProlymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

  • Incidence of grade II-IV acute graft-versus-host disease

    Determine if 3:1 ratio of Treg:CD3+ cells reduces the risk grade II-IV acute graft versus host disease of 20% by day 100 as compared to patients with hematological malignancy receiving same conditioning regimen and immunosuppression but no Tregs.

    Day +100

Secondary Outcomes (9)

  • Incidence of double and single unit chimerism

    Day +100

  • Incidence of grade III-IV acute graft-versus-host disease

    Day +100

  • Incidence of viral and fungal infections

    1 year

  • Survival

    1 year

  • Incidence of neutrophil recovery

    Day 42

  • +4 more secondary outcomes

Study Arms (2)

TREG

EXPERIMENTAL

T regulatory cells after non-myeloablative (using fludarabine, cyclophosphamide, and total body irradiation) umbilical cord transplant.

Biological: T Regulatory cellsDrug: FludarabineDrug: CyclophosphamideRadiation: Total Body Irradiation

Non-Myeloablative Only

EXPERIMENTAL

Non-myeloablative (using fludarabine, cyclophosphamide, and total body irradiation) umbilical cord transplant.

Drug: FludarabineDrug: CyclophosphamideRadiation: Total Body Irradiation

Interventions

T Regulatory cellsBIOLOGICAL

Fixed dose of nTreg cells will be infused on day 0 of transplant after the umbilical cord blood cells

Also known as: nTreg, Treg
TREG
FludarabineDRUG

Fludarabine 30mg/m\^2 IV over 1 hour on days -6 through -2 from transplant

Also known as: Fludara
Non-Myeloablative OnlyTREG
CyclophosphamideDRUG

Cyclophosphamide 50 mg/kg IV over 2 hours on day -6 from transplant

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune
Non-Myeloablative OnlyTREG
Total Body IrradiationRADIATION

Total Body Irradiation (TBI) 200 cGy administered on day -1 in a single fraction will be given at a dose rate of 10-19 cGy/minute prescribed to the midplane of the patient at the level of the umbilicus.

Also known as: TBI
Non-Myeloablative OnlyTREG

Eligibility Criteria

Age18 Years - 69 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Must be ≥18, but \< 70 years of age with no matched 5/6 or 6/6 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 (Appendix II)
  • Three UCB units composing the graft will be selected according to the current University of Minnesota umbilical cord blood graft selection algorithm.
  • Each UCB unit must be matched at 4-6 HLA-A, B, DRB1 antigens with the recipient. This may include 0-2 antigen mismatches at the A or B or DRB1 loci. Each unit must be a 4-6 HLA-A, B, DRB1 antigen match to each other, not necessarily at the same loci they are matched to the recipient.
  • Disease Criteria
  • Acute Leukemias: Must be in remission by morphology (\<5% blasts). Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable. Also a small percentage of blasts that is equivocal between marrow regeneration versus early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse.
  • Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT considered favorable-risk as defined by the presence of at least one of the following:
  • Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), other MLL rearrangements
  • White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
  • Recipient age older than 30 years at diagnosis
  • Time to CR greater than 4 weeks
  • Acute Myelogenous Leukemia (AML) in first complete remission (CR1) that is NOT considered as favorable-risk. Favorable risk is defined as having one of the following:
  • t(8,21) without CKIT mutation
  • inv(16) without CKIT mutation or t(16;16)
  • Normal karyotype with mutated NPM1 and not FLT-IND
  • Normal karyotype with double mutated CEBPA
  • +18 more criteria

You may not qualify if:

  • Untreated active infection at time of transplantation
  • History of HIV infection
  • Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
  • Prior allogeneic transplantation
  • Less than 3 months from myeloablative conditioning for autologous transplantation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Hematologic NeoplasmsBurkitt LymphomaLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMyelodysplastic SyndromesDendritic Cell Sarcoma, InterdigitatingHodgkin DiseaseMultiple MyelomaLeukemia, Lymphocytic, Chronic, B-CellLymphoma, B-Cell, Marginal ZoneLymphoma, FollicularLymphoma, Mantle-CellLeukemia, Prolymphocytic

Interventions

fludarabinefludarabine phosphateCyclophosphamideWhole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, MyeloidLeukemiaMyeloproliferative DisordersBone Marrow DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsHistiocytic Disorders, MalignantHistiocytosisNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLeukemia, B-CellLeukemia, Lymphoid

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsRadiotherapyTherapeuticsInvestigative Techniques

Study Officials

  • Claudio Brunstein, MD, PhD

    University of Minnesota

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 26, 2014

First Posted

April 21, 2014

Study Start

June 1, 2016

Primary Completion

September 1, 2018

Study Completion

September 1, 2018

Last Updated

December 2, 2017

Record last verified: 2017-11

Locations

US(1)