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

NCT ID: NCT01634217

Last Updated: 2019-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-08
• Study Completion Date: 2018-12-01

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.

Conditions

Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Non-Hodgkin Lymphoma; Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Multiple Myeloma; Myelodysplastic Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

Administered 3 x 10\^6 iTregs/kg infusion

Group Type: EXPERIMENTAL

iTreg

Intervention Type: BIOLOGICAL

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).

Cohort 2

Administered 3 x 10\^7 iTregs/kg infusion

Group Type: EXPERIMENTAL

iTreg

Intervention Type: BIOLOGICAL

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).

Cohort 3

Administered 3 x 10\^8 iTregs/kg infusion

Group Type: EXPERIMENTAL

iTreg

Intervention Type: BIOLOGICAL

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).

Cohort 4

Administered 10 x 10\^8 iTregs/kg infusion

Group Type: EXPERIMENTAL

iTreg

Intervention Type: BIOLOGICAL

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).

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.

Group Type: EXPERIMENTAL

iTreg

Intervention Type: BIOLOGICAL

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).

Interventions

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).

Intervention Type: BIOLOGICAL

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Margaret MacMillan, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

References

MacMillan ML, Hippen KL, McKenna DH, Kadidlo D, Sumstad D, DeFor TE, Brunstein CG, Holtan SG, Miller JS, Warlick ED, Weisdorf DJ, Wagner JE, Blazar BR. First-in-human phase 1 trial of induced regulatory T cells for graft-versus-host disease prophylaxis in HLA-matched siblings. Blood Adv. 2021 Mar 9;5(5):1425-1436. doi: 10.1182/bloodadvances.2020003219.

Reference Type: DERIVED

PMID: 33666654 (View on PubMed)

Other Identifiers

MT2012-06R

Identifier Type: OTHER

Identifier Source: secondary_id

2012LS019

Identifier Type: -

Identifier Source: org_study_id