Treg Cells for AGVHD in Non-myeloablative UCB Transplant

NCT ID: NCT02118311

Last Updated: 2017-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-30

Study Completion Date

2018-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Hematologic Malignancies

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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TREG

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

Group Type EXPERIMENTAL

T Regulatory cells

Intervention Type BIOLOGICAL

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

Fludarabine

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

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

Total Body Irradiation

Intervention Type RADIATION

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.

Non-Myeloablative Only

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

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

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

Total Body Irradiation

Intervention Type RADIATION

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.

Interventions

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T Regulatory cells

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

Intervention Type BIOLOGICAL

Fludarabine

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

Intervention Type DRUG

Cyclophosphamide

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

Intervention Type DRUG

Total Body Irradiation

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.

Intervention Type RADIATION

Other Intervention Names

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nTreg Treg Fludara Endoxan Cytoxan Neosar Procytox Revimmune TBI

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Claudio Brunstein, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

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University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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MT2013-27

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA065493

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2013LS091

Identifier Type: -

Identifier Source: org_study_id