Clinical Trials /

Treg Cells for AGVHD in Non-myeloablative UCB Transplant

NCT02118311

Description:

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.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Acute Promyelocytic Leukemia
  • Adult T-Cell Leukemia/Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Chronic Myeloid Leukemia
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Mature T-Cell and NK-Cell Lymphoma/Leukemia
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Prolymphocytic Leukemia
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Treg Cells for AGVHD in Non-myeloablative UCB Transplant
  • Official Title: T Regulatory Cell for Suppression of Acute Graft-vs-Host-Disease in Recipients of a Non-Myeloablative Umbilical Cord Blood Transplantation for Treatment of Hematological Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 2013LS091
  • SECONDARY ID: MT2013-27
  • SECONDARY ID: P01CA065493
  • NCT ID: NCT02118311

Conditions

  • Hematologic Malignancies

Interventions

DrugSynonymsArms
T Regulatory cellsnTreg, TregTREG
FludarabineFludaraTREG
CyclophosphamideEndoxan, Cytoxan, Neosar, Procytox, RevimmuneTREG

Purpose

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 Arms

NameTypeDescriptionInterventions
TREGExperimentalT regulatory cells after non-myeloablative (using fludarabine, cyclophosphamide, and total body irradiation) umbilical cord transplant.
  • Fludarabine
  • Cyclophosphamide
Non-Myeloablative OnlyExperimentalNon-myeloablative (using fludarabine, cyclophosphamide, and total body irradiation) umbilical cord transplant.
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          -  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

               -  APL in first molecular remission at end of consolidation

          -  Acute Leukemias in 2nd or subsequent CR

          -  Biphenotypic/Undifferentiated in first or subsequent CR, adult T-cell
             leukemia/lymphoma in first or subsequent complete remission (CR)

               -  Burkitt's Lymphoma in CR2 or subsequent complete remission (CR)

               -  Natural Killer Cell Malignancies

               -  Chronic Myelogenous Leukemia: all types except refractory blast crisis. Chronic
                  phase patients must have failed or been intolerant to at least one
                  tyrosine-kinase inhibitor

               -  Myelodysplastic Syndrome: any subtype including refractory anemia (RA) if severe
                  pancytopenia or complex cytogenetics. Blasts must be less than 5%. If 5% or more
                  requires induction therapy pre-transplant to reduce blast count to ≤5%.

               -  Large-Cell Lymphoma, Hodgkin Lymphoma and Multiple Myeloma with chemotherapy
                  sensitive disease that has failed or patients who are ineligible for an
                  autologous transplant.

               -  Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone
                  B-Cell Lymphoma, Follicular Lymphoma, which have progressed within 12 months of
                  achieving a partial or complete remission. Patients who had remissions lasting >
                  12 months, are eligible after at least two prior therapies. Patients with bulky
                  disease should be considered for debulking chemotherapy before transplant.
                  Patients with refractory disease are eligible, unless has bulky disease and an
                  estimated tumor doubling time of less than one month.

               -  Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are
                  eligible after initial therapy if chemotherapy sensitive.

        Patients must have undergone an autologous transplant ≤ 12 months prior to allogeneic
        transplantation or have received multi-agent or immunosuppressive chemotherapy within 3
        months of the preparative regimen.

          -  Adequate performance status defined as a Karnofsky score ≥ 70%

          -  Adequate organ function within 14 days (30 days for cardiac and pulmonary) of
             enrollment defined as:

               -  Renal: creatinine < 2.0 mg/dL, for patient with a creatinine > 1.2 mg/dL or a
                  history of renal dysfunction an estimated glomerular filtration rate > 40
                  mL/min/1.73 m2 is required

               -  Hepatic: bilirubin, AST, ALT, alkaline phosphatase < 5 x upper limit of normal,

               -  Pulmonary function: DLCOcorr > 40% normal,

               -  Cardiac: left ventricular ejection fraction > 35%

          -  Voluntary written consent signed before performance of any study-related procedure not
             part of normal medical care

        Exclusion Criteria:

          -  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
      
Maximum Eligible Age:69 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of grade II-IV acute graft-versus-host disease
Time Frame:Day +100
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Incidence of double and single unit chimerism
Time Frame:Day +100
Safety Issue:
Description:Compare the incidence of double and single unit chimerism at day +100 between Treg and controls
Measure:Incidence of grade III-IV acute graft-versus-host disease
Time Frame:Day +100
Safety Issue:
Description:Compare the incidence of grade III-IV aGVHD between Treg and controls
Measure:Incidence of viral and fungal infections
Time Frame:1 year
Safety Issue:
Description:Compare the incidence of viral and fungal infections at 1 year between Treg and controls
Measure:Survival
Time Frame:1 year
Safety Issue:
Description:Compare the probability of survival at 1 year between Treg and controls
Measure:Incidence of neutrophil recovery
Time Frame:Day 42
Safety Issue:
Description:Compare the incidence of neutrophil recovery at day 42 between Treg and controls
Measure:Incidence of treatment related mortality
Time Frame:6 months
Safety Issue:
Description:Determine the incidence of treatment related mortality (TRM) at 6 months between Treg and controls
Measure:Incidence of platelet recovery
Time Frame:1 year
Safety Issue:
Description:Compare the incidence of platelet recovery at 1 year between Treg and controls
Measure:Incidence of chronic GVHD
Time Frame:1 year
Safety Issue:
Description:Compare the incidence of chronic GVHD at 1 year between Treg and controls
Measure:Incidence of relapse
Time Frame:1 year
Safety Issue:
Description:Compare the incidence of relapse at 1 year between Treg and controls

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:Masonic Cancer Center, University of Minnesota

Trial Keywords

  • Acute Leukemias
  • Burkitt's Lymphoma
  • Natural Killer Cell Malignancies
  • Chronic Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • Large-Cell Lymphoma
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Marginal Zone B-Cell Lymphoma
  • Follicular Lymphoma:
  • Lymphoplasmacytic Lymphoma
  • Mantle-Cell Lymphoma
  • Prolymphocytic Leukemia

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