Recruitment

Recruitment Status
Withdrawn
Estimated Enrollment
42

Inclusion Criteria

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 has not started any new systemic immunosuppressive therapies within 2 weeks prior to enrollment
Subject agrees to comply with the study requirements and agrees to come to the clinic for required study visits
...
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 has not started any new systemic immunosuppressive therapies within 2 weeks prior to enrollment
Subject agrees to comply with the study requirements and agrees to come to the clinic for required study visits
Active cGVHD despite treatment with at least two immunosuppressive treatments (not including GVHD prophylaxis) in the past year
Subject has moderate or severe overlap chronic (c)GVHD according to National Institutes of Health (NIH) criteria
Subject underwent allogeneic stem cell transplantation at least 6 months prior to enrollment
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

Exclusion Criteria

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
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
Tuberculosis requiring treatment within the past 3 years; all patients must have a negative quantiferon test within 4 weeks prior to starting study drug
...
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
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
Tuberculosis requiring treatment within the past 3 years; all patients must have a negative quantiferon test within 4 weeks prior to starting study drug
Donor lymphocyte infusion in the preceding 100 days
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper limit of normal (ULN)
Pregnant or breast-feeding women
History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
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
Uncontrolled bacterial, viral infection or invasive fungal infection
History of demyelinating disorder
Total bilirubin > upper limit of normal (ULN)
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
Subject has bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia or cryptogenic organizing pneumonia as the sole manifestation of cGVHD
Immunization with a live, attenuated vaccine within 4 weeks prior to study enrollment
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
Absolute neutrophil count < 1.5 x 10^9/L (1500/mm^3)
Patients (both men and women) with reproductive potential not willing to use an effective method of contraception

Summary

Conditions
  • Graft -Versus-host-disease
  • Graft Versus Host Disease
Type
Interventional
Phase
Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Supportive Care

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

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 ...

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.

Inclusion Criteria

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 has not started any new systemic immunosuppressive therapies within 2 weeks prior to enrollment
Subject agrees to comply with the study requirements and agrees to come to the clinic for required study visits
...
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 has not started any new systemic immunosuppressive therapies within 2 weeks prior to enrollment
Subject agrees to comply with the study requirements and agrees to come to the clinic for required study visits
Active cGVHD despite treatment with at least two immunosuppressive treatments (not including GVHD prophylaxis) in the past year
Subject has moderate or severe overlap chronic (c)GVHD according to National Institutes of Health (NIH) criteria
Subject underwent allogeneic stem cell transplantation at least 6 months prior to enrollment
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

Exclusion Criteria

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
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
Tuberculosis requiring treatment within the past 3 years; all patients must have a negative quantiferon test within 4 weeks prior to starting study drug
...
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
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
Tuberculosis requiring treatment within the past 3 years; all patients must have a negative quantiferon test within 4 weeks prior to starting study drug
Donor lymphocyte infusion in the preceding 100 days
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper limit of normal (ULN)
Pregnant or breast-feeding women
History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
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
Uncontrolled bacterial, viral infection or invasive fungal infection
History of demyelinating disorder
Total bilirubin > upper limit of normal (ULN)
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
Subject has bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia or cryptogenic organizing pneumonia as the sole manifestation of cGVHD
Immunization with a live, attenuated vaccine within 4 weeks prior to study enrollment
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
Absolute neutrophil count < 1.5 x 10^9/L (1500/mm^3)
Patients (both men and women) with reproductive potential not willing to use an effective method of contraception

Locations

Rochester, Minnesota, 55905
Milwaukee, Wisconsin, 53226
Nashville, Tennessee, 37232
Phoenix, Arizona, 85054
Seattle, Washington, 98109
...
Rochester, Minnesota, 55905
Milwaukee, Wisconsin, 53226
Nashville, Tennessee, 37232
Phoenix, Arizona, 85054
Seattle, Washington, 98109

Tracking Information

NCT #
NCT02174263
Collaborators
National Cancer Institute (NCI)
Investigators
  • Principal Investigator: Stephanie Lee Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  • Stephanie Lee Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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