NCT00602693

Brief Summary

RATIONALE: Giving chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T-regulatory cells after the transplant may decrease this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. However, the donor immune system may also react against the recipient's tissues (graft-versus-host disease). PURPOSE: This phase I trial is studying the side effects and best dose of donor T-regulatory cells after an umbilical cord blood transplant in treating patients with advanced hematologic cancer or other disorder.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
41

participants targeted

Target at P50-P75 for phase_1 leukemia

Timeline
Completed

Started Jul 2007

Longer than P75 for phase_1 leukemia

Geographic Reach
1 country

1 active site

Status
completed

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

Study Start

First participant enrolled

July 23, 2007

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

January 10, 2008

Completed
18 days until next milestone

First Posted

Study publicly available on registry

January 28, 2008

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 25, 2014

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 16, 2015

Completed
Last Updated

December 2, 2017

Status Verified

November 1, 2017

Enrollment Period

7.2 years

First QC Date

January 10, 2008

Last Update Submit

November 29, 2017

Conditions

LeukemiaLymphomaMultiple MyelomaPlasma Cell NeoplasmMyelodysplastic Syndromes

Keywords

chronic myelogenous leukemiarecurrent mantle cell lymphomaprolymphocytic leukemiaadvanced chronic lymphocytic leukemiasmall lymphocytic lymphomaB-cell lymphomafollicular lymphomadiffuse large cell lymphomaanaplastic large cell lymphomaHodgkin lymphomamultiple myeloma

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose

    Nine dose levels of CD4+CD25+ Treg are scheduled with the doses being 1, 3, 10, 30, 30+30, 100, 300, 1000, and 3000 x 10\^5 Treg/kg recipient body weight. The dose escalation will proceed in cohorts of one patient until the first dose limiting toxicity (DLT) is observed.

    48 Hours

Secondary Outcomes (11)

  • Number of patients with detectable Treg cells

    Days 0, +1, +3, +7, and +14 after Treg cell infusion

  • Number of Patients with grade II-IV and grade III-IV acute graft versus host disease (GVHD)

    Day 100

  • Number of patients with sustained donor engraftment

    Day 100

  • Number of patients with double chimerism

    6 Months and 1 Year

  • Incidence of neutrophil recovery after umbilical cord blood (UCB) transplantation

    Day 42

  • +6 more secondary outcomes

Study Arms (1)

UCB post-transplant Treg Cell Infusion

EXPERIMENTAL

Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant. Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.

Biological: umbilical cord blood transplantationDrug: AllopurinolDrug: fludarabine phosphateDrug: CyclophosphamideRadiation: Total body irradiationBiological: Treg infusionDrug: Sirolimus

Interventions

umbilical cord blood transplantationBIOLOGICAL

Infusion of umbilical cord blood

Also known as: UCB transplant
UCB post-transplant Treg Cell Infusion
AllopurinolDRUG

Administration begins Day -7 through Day 0, tablet or powder prescribed on an individual basis.

Also known as: Zyloprim
UCB post-transplant Treg Cell Infusion
fludarabine phosphateDRUG

40 mg/m\^2 intravenously over 1 hour on Days -6, -5, -4, -3, -2

Also known as: Fludara
UCB post-transplant Treg Cell Infusion
CyclophosphamideDRUG

50 mg/kg intravenous over 2 hours on Day -6

Also known as: Cytoxan
UCB post-transplant Treg Cell Infusion
Total body irradiationRADIATION

200 cGy on Day -1

Also known as: radiation
UCB post-transplant Treg Cell Infusion
Treg infusionBIOLOGICAL

Infusion of T regulatory cells on Day +1 (also Day +15 for Dose level 5 only). Dose escalation ranges include 1, 3, 10, 30, 100, 300 1000, and 300 x 10\^5 Treg/kg.

Also known as: Treg cells
UCB post-transplant Treg Cell Infusion
SirolimusDRUG

Beginning on day -3 and continuing until day +100, patients receive sirolimus intravenously (IV) with 8-12 mg oral loading dose followed by a single dose of 4mg/day with a target serum concentration of 3-12 mg/mL with a taper until day +180.

Also known as: Rapamune®
UCB post-transplant Treg Cell Infusion

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Ages 18 to 75 years old
  • Eligible for and co-enrolled on protocol UMN-2005LS036, for treatment of any of the following advanced hematologic malignancies:
  • Acute leukemias in complete remission (high risk CR1 or subsequent CR); chronic myelogenous leukemia (except refractory blast crisis); myelodysplastic syndrome with severe pancytopenia or complex cytogenetics, large-cell lymphoma, Hodgkin's lymphoma and multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, marginal zone b-cell lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia may be eligible after initial therapy.
  • Have three partially HLA matched umbilical cord blood (UCB) units (1-2 units for UCB transplantation per MT2005-02 and 1 unit for the Treg cell infusion.)
  • Adequate organ function

You may not qualify if:

  • Patients not exposed to highly immunosuppressive single agent or multi-agent chemotherapy within 3 months, or an ablative preparative regimen for autologous hematopoietic stem cell transplant (HCT) within 1 year.
  • Pregnancy or breastfeeding
  • Current active serious infection
  • Evidence of human immunodeficiency virus (HIV) or known HIV positive serology
  • Patients with acute leukemia in morphologic relapse/persistent disease defined as \>5% blasts in a \> or = 15% cellular bone marrow or any % blasts if blasts have unique morphologic markers (e.g., Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible.
  • Chronic myelogenous leukemia in refractory blast crisis.
  • Active central nervous system malignancy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

  • Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, Defor T, Levine BL, June CH, Rubinstein P, McGlave PB, Blazar BR, Wagner JE. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011 Jan 20;117(3):1061-70. doi: 10.1182/blood-2010-07-293795. Epub 2010 Oct 15.

    PMID: 20952687DERIVED

MeSH Terms

Conditions

LeukemiaLymphomaMultiple MyelomaNeoplasms, Plasma CellMyelodysplastic SyndromesLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLymphoma, Mantle-CellLeukemia, ProlymphocyticLeukemia, Lymphocytic, Chronic, B-CellLymphoma, B-CellLymphoma, FollicularLymphoma, Large B-Cell, DiffuseLymphoma, Large-Cell, AnaplasticHodgkin Disease

Interventions

Cord Blood Stem Cell TransplantationAllopurinolfludarabine phosphateCyclophosphamideWhole-Body IrradiationRadiationSirolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersBone Marrow DiseasesLeukemia, MyeloidMyeloproliferative DisordersChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, Non-HodgkinLeukemia, LymphoidLeukemia, B-CellLymphoma, T-Cell

Intervention Hierarchy (Ancestors)

Stem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsRadiotherapyInvestigative TechniquesPhysical PhenomenaMacrolidesLactones

Study Officials

  • Claudio G. Brunstein, MD, PhD

    Masonic Cancer Center, University of Minnesota

    PRINCIPAL INVESTIGATOR

  • Margaret L. MacMillan, MD

    Masonic Cancer Center, University of Minnesota

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2008

First Posted

January 28, 2008

Study Start

July 23, 2007

Primary Completion

September 25, 2014

Study Completion

April 16, 2015

Last Updated

December 2, 2017

Record last verified: 2017-11

Locations

US(1)