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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01634217
• Other study ID #: 2012LS019
• Secondary ID: MT2012-06R
• Status: Completed
• Phase: Phase 1
• Start date: November 8, 2013
• Est. completion date: December 1, 2018

Study information

• Verified date: January 2019
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 1, 2018
• Est. primary completion date: December 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia
• Acute Myelogenous Leukemia
• Chronic Lymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Hodgkin Disease
• Hodgkin Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Non-Hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

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).

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of grade 3-5 infusional toxicity	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)]	Within 48 Hours After iTregs Administration
Secondary	Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD)	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).	Day 100
Secondary	Incidence of chronic graft-versus-host disease (GVHD)	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
Secondary	Relapse of Disease	The return of signs and symptoms of a disease after a remission.	12 Months
Secondary	Survival	Number (count) of patients alive at 1 year after treatment.	1 Year
Secondary	Survival	Number (count) of patients alive at Day 100.	Day 100