Ustekinumab for the Prevention of Acute Graft-versus-Host Disease After Unrelated Donor Hematopoietic Cell Transplant

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Active, not recruiting; Phase 2

Conditions: Hematologic and Lymphocytic Disorder; Hematopoietic and Lymphoid System Neoplasm

Treatments: Biological: Ustekinumab; Drug: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Study type: Interventional

Funder types: Other

Identifiers

NCT04572815

10421 (Other Identifier)

R01FD006836

NCI-2020-02617 (Registry Identifier)

RG1005588

Details and patient eligibility

About

This phase II trial studies how well ustekinumab works in preventing acute graft-versus-host disease after unrelated donor hematopoietic cell transplant. Sometimes the transplanted cells from a donor can attack the body's normal tissues (called graft-versus-host disease). Giving ustekinumab after the transplant may help prevent acute graft-versus-host disease by controlling the body's immune response. Funding Source- FDA OOPD.

Full description

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab intravenously (IV). Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab subcutaneously (SC) on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

ARM II: Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive a placebo IV. Beginning 8 weeks after IV placebo, patients receive a placebo SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence grade III-IV acute GVHD, of disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

After completion of study, patients are followed up at 6, 9, 12, 18, and 24 months post-HCT.

Enrollment: 116 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18 - 70

• Signed informed consent.

• Hematologic malignancy or disorder requiring allogeneic hematopoietic cell transplantation

• Adequate vital organ function:

  1. Left ventricular ejection fraction (LVEF) ≥ 50%
  2. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 50% of predicted values on pulmonary function tests
  3. Transaminases (aspartate aminotransferase [AST], aspartate aminotransferase [ALT]) < 3 times upper limit of normal values
  4. Creatinine clearance ≥ 50 cc/min.

• Performance status: Karnofsky Performance Status Score ≥ 70%.

• HCT donor is at least 8/8 (matched at HLA-A, -B, -C, -DRB1) matched with the recipient

• PBSC (peripheral blood mobilized stem cells) as graft source

• Fully myeloablative, reduced-toxicity ablative, or reduced-intensity conditioning regimens. If melphalan is part of the conditioning regimen, dose must be at least 75mg/m^2

Exclusion criteria

• Active infection not controlled with appropriate antimicrobial therapy
• Human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection
• Anti-thymocyte globulin (ATG) as part of the conditioning regimen or GVHD prophylaxis
• Pregnant or nursing women
• Subjects of childbearing age unwilling to use an effective birth control method or refrain from sexual intercourse until 15 weeks after last dose of study drug
• Non-myeloablative conditioning regimens or conditioning regimens that use less than 75mg/m^2 of melphalan
• Prior allogeneic transplant
• Non-malignant blood disorders (e.g. sickle cell disease, aplastic anemia)
• Positive screening test for tuberculosis

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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116 participants in 2 patient groups, including a placebo group

Arm I (ustekinumab)

Experimental group

Description:

Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive ustekinumab IV. Beginning 8 weeks after receiving IV ustekinumab, patients receive ustekinumab SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

Treatment:

Other: Questionnaire Administration

Other: Quality-of-Life Assessment

Biological: Ustekinumab

Arm II (placebo)

Placebo Comparator group

Description:

Between 4 and 72 hours prior to start of HCT conditioning therapy, patients receive a placebo IV. Beginning 8 weeks after IV placebo, patients receive a placebo SC on days 50 (+/- 5 days), 100 (+/- 7 days), and 160 (+/- 7 days) post-HCT in the absence of grade III-IV acute GVHD, disease relapse, or unacceptable toxicity. NOTE: HCT infusion takes place on day 0.

Treatment:

Other: Questionnaire Administration

Other: Quality-of-Life Assessment

Drug: Placebo Administration