Clinical trial NCT01634217: Inducible Regulatory T Cells (iTregs) in Non-Myeloablative Sibling Donor Peripheral Blood Stem Cell Transplantation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Chronic Myelogenous Leukemia
Non-Hodgkin Lymphoma
Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Multiple Myeloma
Myelodysplastic Syndrome
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2012-07-06
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of grade 3-5 infusional toxicity
timeFrame: Within 48 Hours After iTregs Administration
Secondary outcomes:
measure: Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD)
timeFrame: Day 100
measure: Incidence of chronic graft-versus-host disease (GVHD)
timeFrame: 12 Months
measure: Relapse of Disease
timeFrame: 12 Months
measure: Survival
timeFrame: 1 Year
measure: Survival
timeFrame: Day 100
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Margaret MacMillan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.