Phase I Study of Infusion of Umbilical Cord Blood (UCB) Derived CD25+CD4+ T-Regulatory (Treg) Cells After Nonmyeloablative Cord Blood Transplantation
18 Years
75 Years
Both
Leukemia, Lymphoma, Multiple Myeloma, Plasma Cell Neoplasm, Myelodysplastic Syndromes
Trial Information
Phase I Study of Infusion of Umbilical Cord Blood (UCB) Derived CD25+CD4+ T-Regulatory (Treg) Cells After Nonmyeloablative Cord Blood Transplantation
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of umbilical cord blood (UCB)-derived
T-regulatory (Treg) cells.
Secondary
- Estimate the proportion of patients with detectable circulating Treg cells at 0, 1, 3,
7, and 14 days after infusion.
- Estimate the risk of grades II-IV and III-IV acute graft versus host disease (GVHD) at
day +100 with the infusion of Treg cells.
- Estimate the proportion of patients with sustained donor engraftment.
- Estimate the proportion of patients with double chimerism at 6 months and 1 year.
- Determine the speed and cumulative incidence of neutrophil recovery by day 42 and
platelet recovery by 6 months after UCB transplantation.
- Estimate the risk of chronic GVHD at 1 year.
- Estimate the probability of disease-free survival at 100 days and 1 year.
- Estimate the risk of fungal and viral infections at 1 year
- Estimate the risk of relapse at 1 year
- Characterize the pattern of immune cell recovery over 1 year
OUTLINE: This is a dose-escalation study of umbilical cord blood (UCB)-derived T-regulatory
(Treg) cells. Patients receive nonmyeloablative UCB transplantation and post-transplant
immunosuppression as in protocol UMN-2005LS036 (without antithymocyte globulin during
conditioning regimen).
- Nonmyeloablative conditioning and UCB transplantation: Patients receive allopurinol on
days -7 to day 0, fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2
and cyclophosphamide IV over 2 hours on day -6; undergo total-body irradiation (TBI)
once on day -1; and undergo UCB transplantation on day 0.
- Immunosuppression therapy: 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. Patients also receive mycophenolate mofetil IV or orally every 8 hours
on days -3 to +30.
- Radiation therapy: total body irradiation is administered on Day -1 of 200 cGy.
- UCB Treg cell infusion: Patients receive escalating doses of UCB-derived CD4+ CD25+
Treg cells IV on day +1 (and Day +15 for dose level 5 only) until the maximum tolerated
dose is obtained.
After completion of study treatment, patients are followed at day 180, 360, and 720.
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose
Outcome Description:
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.
Outcome Time Frame:
48 Hours
Safety Issue:
Yes
Principal Investigator
Claudio G. Brunstein, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Masonic Cancer Center, University of Minnesota
Authority:
United States: Food and Drug Administration
Study ID:
2007LS022
NCT ID:
NCT00602693
Start Date:
July 2007
Completion Date:
July 2016
Related Keywords:
- Leukemia
- Lymphoma
- Multiple Myeloma
- Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- relapsing chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- accelerated phase chronic myelogenous leukemia
- recurrent mantle cell lymphoma
- prolymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage IV small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- stage III grade 1 follicular lymphoma
- stage IV grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- contiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- recurrent adult diffuse large cell lymphoma
- stage I adult diffuse large cell lymphoma
- stage III adult diffuse large cell lymphoma
- stage IV adult diffuse large cell lymphoma
- recurrent childhood anaplastic large cell lymphoma
- stage I childhood anaplastic large cell lymphoma
- stage II childhood anaplastic large cell lymphoma
- stage III childhood anaplastic large cell lymphoma
- stage IV childhood anaplastic large cell lymphoma
- childhood diffuse large cell lymphoma
- childhood immunoblastic large cell lymphoma
- recurrent childhood large cell lymphoma
- recurrent adult Hodgkin lymphoma
- stage I adult Hodgkin lymphoma
- stage II adult Hodgkin lymphoma
- stage III adult Hodgkin lymphoma
- stage IV adult Hodgkin lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- stage I childhood Hodgkin lymphoma
- stage II childhood Hodgkin lymphoma
- stage III childhood Hodgkin lymphoma
- stage IV childhood Hodgkin lymphoma
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- extramedullary plasmacytoma
- isolated plasmacytoma of bone
- monoclonal gammopathy of undetermined significance
- primary systemic amyloidosis
- refractory multiple myeloma
- refractory anemia with ringed sideroblasts
- refractory anemia
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute myeloid leukemia in remission
- recurrent adult acute myeloid leukemia
- untreated adult acute myeloid leukemia
- childhood myelodysplastic syndromes
- childhood acute myeloid leukemia in remission
- recurrent childhood acute myeloid leukemia
- untreated childhood acute myeloid leukemia and other myeloid malignancies
- secondary acute myeloid leukemia
- adult acute lymphoblastic leukemia in remission
- recurrent adult acute lymphoblastic leukemia
- childhood acute lymphoblastic leukemia in remission
- recurrent childhood acute lymphoblastic leukemia
- contiguous stage II adult lymphoblastic lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent childhood lymphoblastic lymphoma
- stage I adult lymphoblastic lymphoma
- stage I childhood lymphoblastic lymphoma
- stage III adult lymphoblastic lymphoma
- stage III childhood lymphoblastic lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV childhood lymphoblastic lymphoma
- atypical chronic myeloid leukemia
- Burkitt lymphoma
- recurrent adult Burkitt lymphoma
- stage III adult Burkitt lymphoma
- stage IV adult Burkitt lymphoma
- adult grade III lymphomatoid granulomatosis
- childhood grade III lymphomatoid granulomatosis
- recurrent adult grade III lymphomatoid granulomatosis
- recurrent childhood grade III lymphomatoid granulomatosis
- chronic myelomonocytic leukemia
- juvenile myelomonocytic leukemia
- recurrent marginal zone lymphoma
- splenic marginal zone lymphoma
- stage III marginal zone lymphoma
- stage IV marginal zone lymphoma
- contiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- stage I adult immunoblastic large cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- recurrent childhood small noncleaved cell lymphoma
- stage III childhood small noncleaved cell lymphoma
- refractory cytopenia with multilineage dysplasia
- refractory anemia with excess blasts in transformation
- refractory anemia with excess blasts
- myelodysplastic/myeloproliferative disease, unclassifiable
- Neoplasms
- Leukemia
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Lymphoma, Large-Cell, Immunoblastic
- Lymphoma, Large-Cell, Anaplastic
Name | Location |
|---|---|
| Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota 55455 |
