Patient case: 11-year-old male with Peutz-Jeghers syndrome; genetic feature: STK11

Clinical trial: Tocilizumab for Chronic Graft-versus-Host Disease Treatment

Summary: This phase II trial studies how well tocilizumab works in treating chronic graft-versus-host disease (GVHD) in patients that have not responded to treatment after at least two prior therapies. Tocilizumab blocks a protein that stimulates the body's immune system. By blocking this protein, the investigators may reduce the symptoms of chronic GVHD.

Detailed description: PRIMARY OBJECTIVES:
  I. Efficacy will be determined by the proportion of patients with failure free survival (FFS) at 6 months.
  SECONDARY OBJECTIVES:
  I. Patients achieving a complete response (CR) or partial response (PR) at 6 months based on clinician judged response.
  II. Patients achieving a CR or PR by objective response measures at 6 months.
  III. Failure-free survival (FFS) at 1 year.
  IV. Change in steroid dose from enrollment to 6 months (mo).
  TERTIARY OBJECTIVES:
  I. Biologic studies will be done to determine possible mechanisms of response.
  OUTLINE:
  Patients receive tocilizumab intravenously (IV) over 1 hour every 2 weeks for 12 weeks (weeks 1, 3, 5, 7, 9, and 11) and then every 4 weeks for 12 weeks (weeks 13, 17, and 21).
  After completion of study treatment, patients are followed up at 3 and 6 months.

Eligibility: Inclusion Criteria:
  -  Subject has moderate or severe overlap chronic (c)GVHD according to National Institutes of Health (NIH) criteria
  -  Active cGVHD despite treatment with at least two immunosuppressive treatments (not including GVHD prophylaxis) in the past year
  -  Subject underwent allogeneic stem cell transplantation at least 6 months prior to enrollment
  -  Subject has not started any new systemic immunosuppressive therapies within 2 weeks prior to enrollment
  -  Female subjects of child bearing potential must have a negative pregnancy test prior to first dose of tocilizumab and must agree to practice effective contraception during the study
  -  Subject meets the following medication restriction requirements and agrees to follow medication restrictions during the study; the following concomitant medications are not allowed: cyclophosphamide, abatacept, etanercept, adalimumab infliximab, golimumab, tofacitinib, and alemtuzumab; these medications also cannot have been used for 5 half-lives prior to enrollment
  -  Subject agrees to comply with the study requirements and agrees to come to the clinic for required study visits
  Exclusion Criteria:
  -  Donor lymphocyte infusion in the preceding 100 days
  -  Subject has bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia or cryptogenic organizing pneumonia as the sole manifestation of cGVHD
  -  Uncontrolled bacterial, viral infection or invasive fungal infection
  -  Evidence of malignancy within 6 months of study enrollment; this is defined as clear morphologic, radiologic or molecular evidence of disease; mixed chimerism is allowed at the discretion of the clinician
  -  Treatment with any non-Food and Drug Administration (FDA) approved agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of study enrollment
  -  Immunization with a live, attenuated vaccine within 4 weeks prior to study enrollment
  -  History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
  -  Tuberculosis requiring treatment within the past 3 years; all patients must have a negative quantiferon test within 4 weeks prior to starting study drug
  -  Pregnant or breast-feeding women
  -  Patients (both men and women) with reproductive potential not willing to use an effective method of contraception
  -  Serum creatinine > 1.6 mg/dL (141 umol/L) in females and > 1.9 mg/dL (168 umol/L) in males; patients with serum creatinine values exceeding these limits are eligible for the study if their estimated glomerular filtration rates (GFR) are > 30 ml/min/1.73 m^2
  -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper limit of normal (ULN)
  -  Total bilirubin > upper limit of normal (ULN)
  -  Absolute neutrophil count < 1.5 x 10^9/L (1500/mm^3)
  -  Known active hepatitis B or C; patients must have a negative test for hepatitis B surface antigen, hepatitis B core antibody and hepatitis C antibody within 4 weeks prior to starting study drug
  -  Known uncontrolled cytomegalovirus (CMV) polymerase chain reaction (PCR) reactivation per institutional standards; once CMV has been treated and stable per institutional standards, patient may be enrolled; CMV PCR will be tested within two weeks prior to starting study drug
  -  History of diverticulitis, Crohn's disease or ulcerative colitis
  -  History of demyelinating disorder

Relevance to patient case: not relevant