Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00602693
Other study ID # 2007LS022
Secondary ID MT2006-010701M00
Status Completed
Phase Phase 1
First received January 10, 2008
Last updated November 29, 2017
Start date July 23, 2007
Est. completion date April 16, 2015

Study information

Verified date November 2017
Source Masonic Cancer Center, University of Minnesota
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 41
Est. completion date April 16, 2015
Est. primary completion date September 25, 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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.

Study Design


Intervention

Biological:
umbilical cord blood transplantation
Infusion of umbilical cord blood
Drug:
Allopurinol
Administration begins Day -7 through Day 0, tablet or powder prescribed on an individual basis.
fludarabine phosphate
40 mg/m^2 intravenously over 1 hour on Days -6, -5, -4, -3, -2
Cyclophosphamide
50 mg/kg intravenous over 2 hours on Day -6
Radiation:
Total body irradiation
200 cGy on Day -1
Biological:
Treg infusion
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.
Drug:
Sirolimus
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.

Locations

Country Name City State
United States Masonic Cancer Center at University of Minnesota Minneapolis Minnesota

Sponsors (1)

Lead Sponsor Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Number of patients with detectable Treg cells determined by polymerase chain reaction (PCR) and flow cytometry Days 0, +1, +3, +7, and +14 after Treg cell infusion
Secondary Number of Patients with grade II-IV and grade III-IV acute graft versus host disease (GVHD) Patients will be assessed weekly for GVHD between days 0 and 100 after transplantation using standard criteria. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. Incidence of grades II-IV and grades III-IV GVHD by day 100 will be monitored. Day 100
Secondary Number of patients with sustained donor engraftment Day 100
Secondary Number of patients with double chimerism 6 Months and 1 Year
Secondary Incidence of neutrophil recovery after umbilical cord blood (UCB) transplantation Day 42
Secondary Number of Patients with Chronic Graft Versus Host Disease (GVHD) 1 Year
Secondary Number of Patients with disease-free survival Day 100 and 1 Year
Secondary Number of Patients with Fungal and Viral Infections Count of reported infections. 1 Year
Secondary Incidence of platelet recovery after umbilical cord blood (UCB) 6 Months After Transplant
Secondary Number of Patients with Disease Relapse 1 Year
Secondary Percent of Patients with Immune Cell Recovery 1 Year
See also
  Status Clinical Trial Phase
Recruiting NCT05027594 - Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02412878 - Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma Phase 3
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Recruiting NCT05971056 - Providing Cancer Care Closer to Home for Patients With Multiple Myeloma N/A
Recruiting NCT05243797 - Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation Phase 3
Active, not recruiting NCT04555551 - MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma Phase 1
Recruiting NCT05618041 - The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies N/A
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Recruiting NCT03570983 - A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion Phase 2
Completed NCT03665155 - First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody Phase 1/Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT02812706 - Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients Phase 1/Phase 2
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Active, not recruiting NCT03792763 - Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients Phase 2
Active, not recruiting NCT03989414 - A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM) Phase 1/Phase 2
Withdrawn NCT03608501 - A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation Phase 2
Recruiting NCT04537442 - Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02546167 - CART-BCMA Cells for Multiple Myeloma Phase 1