Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Inducible Regulatory T Cells (iTregs) in Non-Myeloablative Sibling Donor Peripheral Blood Stem Cell Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01634217
Recruitment Status : Completed
First Posted : July 6, 2012
Last Update Posted : January 18, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE July 2, 2012
First Posted Date  ICMJE July 6, 2012
Last Update Posted Date January 18, 2019
Actual Study Start Date  ICMJE November 8, 2013
Actual Primary Completion Date December 1, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2012)
Incidence of grade 3-5 infusional toxicity [ Time Frame: Within 48 Hours After iTregs Administration ]
Targeted adverse events and unexpected events not explained by the PBSCT or disease will be collected [(1-4 hours after the iTreg infusion and before the PBSCT at day 0) and 24 hours and 48 hours after the iTreg infusion (+/- 2 hours)]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01634217 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2012)
  • Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) [ Time Frame: Day 100 ]
    Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Abstracted from the routine clinical data collected for the primary transplant protocol (MT2001-10).
  • Incidence of chronic graft-versus-host disease (GVHD) [ Time Frame: 12 Months ]
    Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Abstracted from the routine clinical data collected for the primary transplant protocol (MT2001-10).
  • Relapse of Disease [ Time Frame: 12 Months ]
    The return of signs and symptoms of a disease after a remission.
  • Survival [ Time Frame: 1 Year ]
    Number (count) of patients alive at 1 year after treatment.
  • Survival [ Time Frame: Day 100 ]
    Number (count) of patients alive at Day 100.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Inducible Regulatory T Cells (iTregs) in Non-Myeloablative Sibling Donor Peripheral Blood Stem Cell Transplantation
Official Title  ICMJE Dose Escalation Study With Extension of Inducible Regulatory T Cells (iTregs) in Adult Patients Undergoing Non-Myeloablative HLA Identical Sibling Donor Peripheral Blood Stem Cell Transplantation
Brief Summary This is a phase I single center dose escalation study with an extension at the best available dose to determine the tolerability of inducible regulatory T cells (iTregs) when given to adult patients undergoing non-myeloablative HLA-identical sibling donor peripheral blood stem cell (PBSC) transplantation for the treatment of a high risk malignancy. Up to 5 dose cohorts will be tested. Once the tolerable dose is determined for iTregs, enrollment will continue with an additional 10 patients using sirolimus/Mycophenolate mofetil (MMF) graft-versus-host disease (GVHD) prophylaxis to gain further safety information and to provide pilot data in this treatment setting.
Detailed Description Co-enrollment in University Of Minnesota protocol MT2001-10 is required and transplantation will be according to that protocol with iTregs administered the morning of day 0 followed no sooner than 4 hours later by the PBSC transplantation.
Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myelogenous Leukemia
  • Acute Lymphocytic Leukemia
  • Chronic Myelogenous Leukemia
  • Non-Hodgkin Lymphoma
  • Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
  • Multiple Myeloma
  • Myelodysplastic Syndrome
Intervention  ICMJE Biological: iTreg
The iTregs will be infused at the assigned dose without a filter or pump slowly by gravity over 15-60 minutes. The iTregs should be given at least 4 hours before the peripheral blood stem cell (PBSC) infusion (MT2001-10).
Study Arms
  • Experimental: Cohort 1
    Administered 3 x 10^6 iTregs/kg infusion
    Intervention: Biological: iTreg
  • Experimental: Cohort 2
    Administered 3 x 10^7 iTregs/kg infusion
    Intervention: Biological: iTreg
  • Experimental: Cohort 3
    Administered 3 x 10^8 iTregs/kg infusion
    Intervention: Biological: iTreg
  • Experimental: Cohort 4
    Administered 10 x 10^8 iTregs/kg infusion
    Intervention: Biological: iTreg
  • Experimental: Cohort 5 Extension
    Administered 10 x 10^8 iTregs/kg or best available dose using sirolimus/MMF as graft-versus-host disease (GVHD) prophylaxis. Immunosuppression will consist of a combination of sirolimus and mycophenolate mofetil (MMF). Sirolimus will be administered starting at day -3 with 8mg-12mg oral loading dose followed by single dose 4 mg/day. MMF will be administered starting on day -3 at a dose of 3 gram/day divided in 2 or 3 doses. Intravenous (IV) route between days -3 and +5, then may change to PO between days +6 and +30. Stop MMF at day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD.
    Intervention: Biological: iTreg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 7, 2016)
16
Original Estimated Enrollment  ICMJE
 (submitted: July 5, 2012)
22
Actual Study Completion Date December 1, 2018
Actual Primary Completion Date December 1, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 18 - 75 years of age with an HLA-identical sibling donor
  • One of the following disease categories:

    • Acute myelogenous leukemia - high risk CR1 (as evidenced by preceding MDS, intermediate to high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery (ANC > 0.5x 109/L), AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
    • Acute lymphocytic leukemia - high risk CR1 [t(9;22), t (1:19), t(4;11) or other MLL rearrangements] or >1cycle to obtain CR; CR2+. All patients must be in CR as defined by hematological recovery (ANC > 0.5x 109/L), AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
    • Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible)
    • Non-Hodgkin lymphoma or Hodgkin lymphoma demonstrating chemosensitive disease
    • Myelodysplastic syndrome with severe pancytopenia, leading to either transfusion dependency or increased risk for infections
  • Performance status: Karnofsky ≥ 60%
  • Adequate organ function within 28 days of study enrollment defined as:

    • Liver: SGOT and SGPT < 5.0 x ULN; total bilirubin < 3 x ULN
    • Renal: serum creatinine < 2.0 mg/dl or glomerular filtration rate (GFR) > 40 mL/min/1.73m2. Patients with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have glomerular filtration rate (GFR) > 40 mL/min/1.73m2
    • Albumin: > 2.5 g/dL
    • Cardiac: No decompensated CHF or uncontrolled arrhythmia; ejection fraction > 35% within 6 weeks prior to study enrollment
    • Pulmonary: No O2 requirements; DLCO > 30% predicted within 6 weeks prior to study enrollment
  • If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease
  • Sexually active females of child bearing potential and males must agree to use effective contraception for the duration of the transplant period
  • Voluntary written consent

Exclusion Criteria:

  • Pregnancy or breast feeding - women of childbearing potential must have a negative pregnancy test within 28 days of study enrollment.
  • Prior myeloablative transplant within previous 3 months of study enrollment.
  • Evidence of HIV infection or known HIV positive serology.
  • Active serious infection.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01634217
Other Study ID Numbers  ICMJE 2012LS019
MT2012-06R ( Other Identifier: University of Minnesota Bone Marrow Transplant Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Margaret MacMillan, MD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP