NCT01163201

Brief Summary

This is a unique dose-escalation trial that will titrate doses of umbilical cord blood (UCB) Treg and CD3+ Teff cells with the goal of infusing as many CD3+ Teff cells as possible without conferring grade II-IV acute graft-versus-host disease (GVHD). In this study, the investigators propose to add UCB Treg and UCB CD3+ Teff cells to the two TCD UCB donor units with the goal of transplanting as many CD3+ Teff cells as possible without reintroducing risk of acute GVHD. The investigators hypothesize that Treg will permit the reintroduction of CD3+ Teff cells that will provide a bridge while awaiting HSC T cell recovery long term. The co-infusion of Treg will prevent GVHD without the need for prolonged pharmacologic immunosuppression.

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 Jan 2014

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withdrawn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

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 26, 2010

Completed
2 months until next milestone

First Posted

Study publicly available on registry

July 15, 2010

Completed
3.5 years until next milestone

Study Start

First participant enrolled

January 1, 2014

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
Last Updated

December 2, 2017

Status Verified

November 1, 2017

Enrollment Period

1 year

First QC Date

May 26, 2010

Last Update Submit

November 29, 2017

Conditions

Hematologic MalignancyAcute Myeloid LeukemiaAcute Lymphocytic LeukemiaChronic Myelogenous Leukemia in Blast CrisisAnemia, Refractory, With Excess of BlastsChronic Myeloproliferative DiseaseChronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaMarginal Zone B-cell LymphomaFollicular LymphomaLymphoplasmacytic LymphomaMantle-Cell LymphomaProlymphocytic LymphomaLarge Cell Non-Hodgkin's LymphomaLymphoblastic LymphomaBurkitt's LymphomaHigh Grade Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

  • Optimal Cell Dose Mixture

    Determine the optimal cell dose mixture of UCB T regulatory and CD3+ T effector cells without the development of grade II-IV acute GVHD

    Day 0

Secondary Outcomes (10)

  • Determine incidence of infusional toxicity

    48 hours

  • Incidence of neutrophil recovery

    Day 42

  • Incidence of double and single chimerism

    Day +21, Day +180, 1 Year

  • Incidence of Viral and Fungal Infections

    1 Year

  • 1 Year Survival

    1 Year

  • +5 more secondary outcomes

Study Arms (1)

Treg Plus CD3+Teff Treatment

EXPERIMENTAL

Includes dose adjustment of T regulatory (Treg) and CD3+ T effector (CD3+ Teff) cells in recipients of double UCB transplantation

Biological: Treg cellsBiological: CD3+ Teff cellsDrug: FludarabineDrug: CyclophosphamideRadiation: Total body irradiationBiological: Umbilical cord blood transplantation

Interventions

Treg cellsBIOLOGICAL

Given by infusion on Day 0 after transplantation - Five doses of Treg (3 x 10\^6/kg, 10 x 10\^6/kg, 30 x 10\^6/kg, 100 x 10\^6/kg and 300 x 10\^6/kg)

Treg Plus CD3+Teff Treatment
CD3+ Teff cellsBIOLOGICAL

Given by infusion on Day 0 after transplantation - 5 doses of CD3+ Teff cells (3 x 10\^6 cells/kg, 6 x 10\^6 cells/kg, 9 x 10\^6 cells/kg, 12 x 10\^6 cells/kg, and 15 x 10\^6 cells/kg with the latter dose representing the median number of CD3+ cells in two UCB unit grafts

Treg Plus CD3+Teff Treatment
FludarabineDRUG

Given intravenously on Days -8 through -6, 25 mg/m\^2 over 1 hour

Also known as: Fludara
Treg Plus CD3+Teff Treatment
CyclophosphamideDRUG

Given intravenously on Day -7 and -6, 60 mg/kg

Also known as: Cytoxan
Treg Plus CD3+Teff Treatment
Total body irradiationRADIATION

Given on Days -4 through -2, 165 cGY twice a day.

Treg Plus CD3+Teff Treatment
Umbilical cord blood transplantationBIOLOGICAL

Infusion given on day 0

Also known as: UCBT
Treg Plus CD3+Teff Treatment

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Only patients requiring a double umbilical cord blood (UCB) transplant are to be considered for this study.
  • UCB Requirements
  • Three UCB units are required - one for Treg production and two for UCB transplant. The unrelated UCB donors must be 4-6/6 HLA-A, B, DRB1 matched with the recipient (HLA matching using molecular techniques: A and B to antigen level resolution and DR to allele level resolution). Suitable UCB units will be selected according to the University Of Minnesota UCB Graft Selection Algorithm.
  • Suitable UCB units must be ABO matched.
  • Disease Criteria:
  • Patients aged 18 to 55 years
  • Acute Myeloid Leukemia: with morphologically persistent disease in a representative bone marrow aspirate sample with ≤ 10% blasts after at least 1 cycles of chemotherapy (if patient refuses or is disqualified from alternative protocols), or in 3rd or higher complete remission (CR).
  • Acute Lymphocytic Leukemia: with morphologically persistent disease in a representative bone marrow aspirate sample with ≤ 10% blasts after at least 1 cycles of chemotherapy, or in 3rd or higher CR
  • Chronic Myelogenous Leukemia in Blast Crisis: with ≤10% residual blasts in the bone marrow aspirate after at least 1 cycle of induction chemotherapy in combination with a tyrosine kinase inhibitor (TKI)
  • Refractory Anemia with Excess Blasts: (≤ 10%) in representative bone marrow aspirate sample of blasts after 1 cycle of induction chemotherapy. If treated with hypomethylating agents, patients are eligible if blast count is ≤ 10% after 4 cycles or evidence of stable or progressive disease after at least 2 cycles.
  • Chronic Myeloproliferative Disease
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma or Follicular Lymphoma: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
  • Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
  • Large Cell Non-Hodgkin's Lymphoma: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
  • Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other High-Grade NHL: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
  • +8 more criteria

You may not qualify if:

  • Available medically suitable HLA-identical related donor
  • Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
  • 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 myeloablative transplant within the last 6 months
  • Extensive prior therapy including \> 12 months alkylator therapy or \> 6 months alkylator therapy with extensive radiation
  • Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar) as part of their salvage therapy (not eligible for myeloablative umbilical cord blood transplant)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55445, United States

Location

MeSH Terms

Conditions

Hematologic NeoplasmsLeukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaAnemia, Refractory, with Excess of BlastsMyeloproliferative DisordersLeukemia, Lymphocytic, Chronic, B-CellLymphoma, B-Cell, Marginal ZoneLymphoma, FollicularLymphoma, Mantle-CellBurkitt Lymphoma

Interventions

fludarabinefludarabine phosphateCyclophosphamideWhole-Body IrradiationCord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesAnemia, RefractoryAnemiaMyelodysplastic SyndromesBone Marrow DiseasesLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, B-CellLymphoma, Non-HodgkinLymphomaEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus Infections

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsRadiotherapyTherapeuticsInvestigative TechniquesStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTransplantationSurgical Procedures, Operative

Study Officials

  • Claudio Brunstein, MD, PhD

    Masonic Cancer Center, University of Minnesota

    PRINCIPAL INVESTIGATOR
0

Study Design

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

Study Record Dates

First Submitted

May 26, 2010

First Posted

July 15, 2010

Study Start

January 1, 2014

Primary Completion

January 1, 2015

Study Completion

January 1, 2015

Last Updated

December 2, 2017

Record last verified: 2017-11

Locations

US(1)