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

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Completed

CT.gov ID

NCT01634217

Collaborator

(none)

Enrollment

Location

Arms

60.7

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

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 :

Nov 8, 2013

Actual Primary Completion Date :

Dec 1, 2017

Actual Study Completion Date :

Dec 1, 2018

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

Incidence of grade 3-5 infusional toxicity [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

Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) [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) [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 [12 Months]
The return of signs and symptoms of a disease after a remission.
Survival [1 Year]
Number (count) of patients alive at 1 year after treatment.
Survival [Day 100]
Number (count) of patients alive at Day 100.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.