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Graft-Versus-Host-DiseasePhase 2NCT01927120

In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis

A Phase 2 study testing IL-2, Tacrolimus and Sirolimus in people with Graft-Versus-Host-Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft-Versus-Host-Disease
What is being tested?
IL-2, Tacrolimus and Sirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
25 Mar 2014to 9 Mar 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 12Show fewer
  • 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.

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis With IL-2, Sirolimus, and Tacrolimus Following Allogeneic Hematopoietic Cell Transplantation

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).

Read the detailed description
  1. Determine if a GVHD prophylaxis regimen of IL-2/SIR/TAC enhances in vivo Treg differentiation and growth; 2) Study the safety and effects of IL-2/SIR/TAC on the incidence of acute and chronic GVHD; 3) Evaluate the influence of dual IL-2 supplementation and mammalian target of rapamycin (mTOR) inhibition on T cell-specific signaling pathways and the polarization of emerging T helper cells.
Being tested
IL-2, Tacrolimus, Sirolimus
Keywords
GVHD, Allogeneic, Hematopoietic Cell Transplant
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IL-2Drug

    Also called Proleukin®, (aldesleukin)

    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).

  • 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

  • SirolimusDrug

    Also called Rapamune

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

Study groups in NCT01927120
Study groupRoleWhat they receive
GVHD RegimenExperimentalGraft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
Receives: Drug: IL-2; Drug: Tacrolimus; Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 30 days post HCT

Secondary outcomes (9)

  1. Overall Survival at Day +365

    Overall survival will be defined as the time from transplant date to death from any cause.

    Measured: 365 days post HCT

  2. Cumulative Incidence of Relapse

    Incidence of primary disease relapse per standard definitions.

    Measured: 1 year post HCT

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

    Acute GVHD will be graded per the 1995 consensus guidelines.

    Measured: 100 days post HCT

  4. Cumulative Incidence of Chronic GVHD by Day +365

    Cumulative incidence of chronic GVHD by day +365 per NIH Consensus criteria.

    Measured: 365 days post HCT

  5. Incidence of Non-relapse Death

    Incidence of Non-relapse death/Transplant-related mortality. Non-relapse death is defined as death in continuous remission from primary disease requiring transplantation.

    Measured: 365 days post HCT

  6. Incidence of Unexpected or Serious Adverse Events (AEs)

    Grade 3-5 unexpected or serious adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.03) were captured up to day +130 or 30 days after the last dose of IL-2. Events listed, with causality in relation to study treatment noted.

    Measured: Up to days 130 post HCT

  7. Proportion of Treg Among Blood CD4+ T Cells at Day +90 After HCT

    The proportion of Tregs to non-Treg CD4+ cells to be assessed at day +90. Natural Killer Cells (NKs): Median K/uL NK cells.

    Measured: 90 days post HCT

  8. STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 30

    Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +30.

    Measured: 30 days post HCT

  9. STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 90

    Phosphorylation (p): pSTAT3, pSTAT5 (Y694), and pS6 among Treg and non-Treg at day +90.

    Measured: 90 days post HCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Aug 2013 (estimated)
  2. Study start25 Mar 2014
  3. Primary completion25 Aug 2016
  4. Study completion9 Mar 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01927120
Sponsor's protocol ID
MCC-17578
Other IDs
NCI-2014-00755
Status last verified
Mar 2017
First submitted
16 Aug 2013
Last updated
2 Jul 2017
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 28104702

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IL-2, Tacrolimus and Sirolimus in people with Graft-Versus-Host-Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT (time frame: 30 days post HCT). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01927120, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.

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