NCT01927120

Brief Summary

IL-2 add-back post allogeneic hematopoietic stem cell transplant (HSCT), combined with Sirolimus (SIR), Tacrolimus (TAC) will optimize Treg reconstitution and prevent graft versus host disease (GVHD).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Mar 2014

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 16, 2013

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 22, 2013

Completed
7 months until next milestone

Study Start

First participant enrolled

March 25, 2014

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 25, 2016

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 9, 2017

Completed
4 months until next milestone

Results Posted

Study results publicly available

July 2, 2017

Completed
Last Updated

July 2, 2017

Status Verified

March 1, 2017

Enrollment Period

2.4 years

First QC Date

August 16, 2013

Results QC Date

April 18, 2017

Last Update Submit

June 1, 2017

Conditions

Graft-Versus-Host-Disease

Keywords

GVHDAllogeneicHematopoietic Cell Transplant

Outcome Measures

Primary Outcomes (1)

  • Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT

    Percentage of Treg among blood CD4+ T cells at day 30 after hematopoietic cell transplantation (HCT), to compare to SIR/TAC alone data from a previous trial (median of 16%). The study was designed to capture an increase in regulatory T cells from a median of 16.0% at day +30.

    30 days post HCT

Secondary Outcomes (9)

  • Overall Survival at Day +365

    365 days post HCT

  • Cumulative Incidence of Relapse

    1 year post HCT

  • Cumulative Incidence of Grade II-IV Acute GVHD by Day +100

    100 days post HCT

  • Cumulative Incidence of Chronic GVHD by Day +365

    365 days post HCT

  • Incidence of Non-relapse Death

    365 days post HCT

  • +4 more secondary outcomes

Other Outcomes (2)

  • Function of Blood Treg After Allogeneic HSCT

    30 days post HCT

  • Rate of Natural Killer Cell (NK) Reconstitution

    365 days post HCT

Study Arms (1)

GVHD Regimen

EXPERIMENTAL

Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).

Drug: IL-2Drug: TacrolimusDrug: Sirolimus

Interventions

IL-2DRUG

A subcutaneous injection will be administered 3 times a week (separated by at least 1 day between injections), from day 0 to +90 (+/- 7 days).

Also known as: Proleukin®, (aldesleukin)
GVHD Regimen
TacrolimusDRUG

Will be administered at 0.01 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3

GVHD Regimen
SirolimusDRUG

Orally on day -1. The dose for loading is 12 mg by mouth (PO)

Also known as: Rapamune
GVHD Regimen

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have an available 8/8 human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 matched-related or unrelated donor allogeneic hematopoietic peripheral blood stem cell graft.
  • Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid leukemia, or myeloproliferative neoplasms requiring a matched allogeneic HSCT.
  • Acute Leukemia (AML or ALL) must be in complete remission defined as: \<5% marrow blasts with no morphologic evidence of leukemia, no peripheral blasts, marrow \>20% cellular, and peripheral absolute neutrophil count \>1000/µL (platelet recovery is not required).
  • Myelodysplasia (MDS) and chronic myeloid leukemia (CML): Must have \<5% marrow blasts.
  • Myeloproliferative neoplasms (MPN): Must have \<5% peripheral / marrow blasts.
  • Adequate vital organ function:
  • Left ventricular ejection fraction (LVEF) ≥ 45% by multi gated acquisition (MUGA) scan or ECHO
  • Forced expiratory volume at one second (FEV1), forced vital capacity (FVC), and adjusted diffusing lung capacity oxygenation (DLCO) ≥ 50% of predicted values on pulmonary function tests
  • Transaminases (AST, ALT) \< 2 times upper limit of normal values
  • Creatinine clearance ≥ 50 cc/min.
  • Performance status: Karnofsky Performance Status Score ≥ 80%
  • Donor eligibility: Eligible donors will include healthy sibling, relative or unrelated donors that are matched with the patient at HLA-A, B, C, and DRB1 by high resolution typing.

You may not qualify if:

  • Active infection not controlled with appropriate antimicrobial therapy
  • History of HIV, hepatitis B, or hepatitis C infection
  • Anti-thymocyte globulin, alemtuzumab, bortezomib, or cyclophosphamide administered within 14 days before or planned to receive with HCT conditioning or as part of GVHD prophylaxis in the 14 days after HCT.
  • Hypersensitivity to recombinant human IL-2
  • Chronic lymphocytic leukemia, Hodgkin lymphoma, and non-hodgkin lymphoma are excluded as these malignancies may express the IL-2 receptor and pose a potential growth signal to any present disease.
  • Sorror's co-morbidity factors with total score \>4

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

  • Betts BC, Pidala J, Kim J, Mishra A, Nishihori T, Perez L, Ochoa-Bayona JL, Khimani F, Walton K, Bookout R, Nieder M, Khaira DK, Davila M, Alsina M, Field T, Ayala E, Locke FL, Riches M, Kharfan-Dabaja M, Fernandez H, Anasetti C. IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation. Haematologica. 2017 May;102(5):948-957. doi: 10.3324/haematol.2016.153072. Epub 2017 Jan 19.

    PMID: 28104702DERIVED

Related Links

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Interleukin-2aldesleukinTacrolimusSirolimus

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

InterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsLymphokinesProteinsBiological FactorsMacrolidesLactonesOrganic Chemicals

Limitations and Caveats

Strategies to overcome interference from soluble IL-2 receptor and STAT3-mediated acute GVHD are needed.

Results Point of Contact

Title
Dr. Brian Betts
Organization
H. Lee Moffitt Cancer Center and Research Institute
brian.betts@moffitt.org
813-745-5410

Study Officials

  • Brian Betts, MD

    Moffitt Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 16, 2013

First Posted

August 22, 2013

Study Start

March 25, 2014

Primary Completion

August 25, 2016

Study Completion

March 9, 2017

Last Updated

July 2, 2017

Results First Posted

July 2, 2017

Record last verified: 2017-03

Locations

US(1)