Tacrolimus, Sirolimus and Ustekinumab vs. Tacrolimus and Sirolimus for the Prevention of Acute Graft-Versus-Host Disease

H. Lee Moffitt Cancer Center and Research Institute

Status and phase: Completed; Phase 2

Conditions: Graft vs. Host Disease

Treatments: Drug: Ustekinumab; Drug: Placebo; Drug: Sirolimus; Drug: Tacrolimus (TAC)

Study type: Interventional

Funder types: Other

Identifiers

NCT01713400

MCC-16743

Details and patient eligibility

About

To determine whether treatment with ustekinumab will alter the ratio of T Regulatory Cell (Treg)/total cluster of differentiation 4 (CD4)+ cells in peripheral blood at day 30 post-hematopoietic cell transplantation (HCT).

Full description

This is a comparative study to assess the biologic and clinical activity of the agent ustekinumab when given in concert with our established regimen of SIR/TAC. Patients will be randomly assigned between the standard regimen of tacrolimus/sirolimus (TAC/SIR + placebo) vs. the investigational regimen of tacrolimus/sirolimus/ustekinumab (TAC/SIR/U) in a 1:1 scheme.

Enrollment: 54 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Hematologic disorder requiring allogeneic hematopoietic cell transplantation
• Adequate vital organ function:
• Left ventricular ejection fraction (LVEF) >/= 45% by multigated acquisition (MUGA) scan
• FEV1, FVC, and diffusing lung capacity oxygenation (DLCO) >/= 50% of predicted values on pulmonary function tests
• Transaminases (AST, ALT) < 3 times upper limit of normal values
• Creatinine clearance >/= 50 cc/min.
• Performance status: Karnofsky Performance Status Score >/= 60%.

Exclusion criteria

• Active infection not controlled with appropriate antimicrobial therapy
• HIV, hepatitis B, or hepatitis C infection
• Sorror's co-morbidity factors with total score > 3
• Important modification to co-morbidity index calculation: DLCO will not be included in assessment of pulmonary risk, excepting those with DLCO < 50%, who will merit a score of 3 and thereby be excluded from the trial.
• Anti-thymocyte globulin (ATG) as part of the conditioning regimen
• Cyclophosphamide as part of the conditioning regimens

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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54 participants in 2 patient groups, including a placebo group

Ustekinumab

Experimental group

Description:

Ustekinumab, Tacrolimus and Sirolimus. Ustekinumab: 45 mg for adults who weight 100 kg or less; 90 mg for adults who weight greater than 100 kg. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.

Treatment:

Drug: Tacrolimus (TAC)

Drug: Sirolimus

Drug: Ustekinumab

Placebo

Placebo Comparator group

Description:

Placebo, Tacrolimus, and Sirolimus. Placebo: Identical volume to that of ustekinumab. Tacrolimus: Level determined according to Blood and Marrow Transplant (BMT) Program standard operating procedures. Sirolimus: The dose for both loading and ongoing administration to be dictated by the standard operating procedures of the BMT program.

Treatment:

Drug: Tacrolimus (TAC)

Drug: Sirolimus

Drug: Placebo