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

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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

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.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Acute Lymphocytic Leukemia Chronic Myelogenous Leukemia Non-Hodgkin Lymphoma Hodgkin Lymphoma Chronic Lymphocytic Leukemia Multiple Myeloma Myelodysplastic Syndrome Biological: iTreg Phase 1

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 : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 8, 2013
Actual Primary Completion Date : December 1, 2017
Actual Study Completion Date : December 1, 2018


Arm Intervention/treatment
Experimental: Cohort 1
Administered 3 x 10^6 iTregs/kg infusion
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).

Experimental: Cohort 2
Administered 3 x 10^7 iTregs/kg infusion
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).

Experimental: Cohort 3
Administered 3 x 10^8 iTregs/kg infusion
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).

Experimental: Cohort 4
Administered 10 x 10^8 iTregs/kg infusion
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).

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.
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).




Primary Outcome Measures :
  1. 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)]


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. Relapse of Disease [ Time Frame: 12 Months ]
    The return of signs and symptoms of a disease after a remission.

  4. Survival [ Time Frame: 1 Year ]
    Number (count) of patients alive at 1 year after treatment.

  5. Survival [ Time Frame: Day 100 ]
    Number (count) of patients alive at Day 100.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01634217


Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Margaret MacMillan, MD Masonic Cancer Center, University of Minnesota

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01634217     History of Changes
Other Study ID Numbers: 2012LS019
MT2012-06R ( Other Identifier: University of Minnesota Bone Marrow Transplant Program )
First Posted: July 6, 2012    Key Record Dates
Last Update Posted: January 18, 2019
Last Verified: January 2019

Additional relevant MeSH terms:
Lymphoma
Leukemia
Multiple Myeloma
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myeloid
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Leukemia, B-Cell