- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01634217
Inducible Regulatory T Cells (iTregs) in Non-Myeloablative Sibling Donor Peripheral Blood Stem Cell Transplantation
January 17, 2019 updated by: Masonic Cancer Center, University of Minnesota
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Enrollment (Actual)
16
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- Masonic Cancer Center, University of Minnesota
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1
Administered 3 x 10^6 iTregs/kg infusion
|
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
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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
|
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
|
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.
|
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).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of grade 3-5 infusional toxicity
Time Frame: Within 48 Hours After iTregs Administration
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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)]
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Within 48 Hours After iTregs Administration
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD)
Time Frame: Day 100
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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).
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Day 100
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Incidence of chronic graft-versus-host disease (GVHD)
Time Frame: 12 Months
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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).
|
12 Months
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Relapse of Disease
Time Frame: 12 Months
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The return of signs and symptoms of a disease after a remission.
|
12 Months
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Survival
Time Frame: 1 Year
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Number (count) of patients alive at 1 year after treatment.
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1 Year
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Survival
Time Frame: Day 100
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Number (count) of patients alive at Day 100.
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Day 100
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Margaret MacMillan, MD, Masonic Cancer Center, University of Minnesota
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 8, 2013
Primary Completion (Actual)
December 1, 2017
Study Completion (Actual)
December 1, 2018
Study Registration Dates
First Submitted
July 2, 2012
First Submitted That Met QC Criteria
July 5, 2012
First Posted (Estimate)
July 6, 2012
Study Record Updates
Last Update Posted (Actual)
January 18, 2019
Last Update Submitted That Met QC Criteria
January 17, 2019
Last Verified
January 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Myeloproliferative Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Leukemia, B-Cell
- Lymphoma
- Myelodysplastic Syndromes
- Multiple Myeloma
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Other Study ID Numbers
- 2012LS019
- MT2012-06R (Other Identifier: University of Minnesota Bone Marrow Transplant Program)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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