Trial Outcomes & Findings for Tocilizumab for Treatment of Steroid Refractory Acute Graft-versus-Host Disease (NCT NCT01475162)

Last Updated: 2020-02-17

Results Overview

Number of subjects achieving Center for International Blood and Marrow Transplant Research (CIBMTR) score of 0 (complete response); or achieving improvement in one or more organs involved in GVHD without progression in other organs (partial response). CIBMTR score of 0 means no evidence of rash or diarrhea and bilirubin less than 2.0 mg/dl. CIBMTR score of 4 means rash with bullae desquamation, lower gastrointestinal diarrhea more than 1,500 ml, and bilirubin greater than 15.1 mg/dl. Higher score means worse disease.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Day 56

Results posted on

2020-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	Tocilizumab Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4 mg/kg once every three weeks depending on graft versus host disease (GVHD) response.
Overall Study STARTED	14
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Tocilizumab Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4 mg/kg once every three weeks depending on graft versus host disease (GVHD) response.
Overall Study Physician Decision	1
Overall Study Death	10
Overall Study Study closed for safety	3

Baseline Characteristics

Tocilizumab for Treatment of Steroid Refractory Acute Graft-versus-Host Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tocilizumab n=14 Participants Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response. Tocilizumab: Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	57 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 56

Population: 6 of the thirteen subjects were not evaluable due to expiring prior to Day 56.

Outcome measures

Outcome measures
Measure	Tocilizumab n=7 Participants Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks.
Number of Subjects Achieving Complete or Partial Response at Day 56 After Administration of Tocilizumab	7 Participants

SECONDARY outcome

Timeframe: Day 56

Population: Six subjects expired prior to day 56.

Number of subjects achieving improvement in one or more organs involved in GVHD with or without deterioration in another organ (mixed or partial response, respectively); or having received additional immune suppressive therapy (no response).

Outcome measures

Outcome measures
Measure	Tocilizumab n=7 Participants Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks.
Number of Patients With Partial, Mixed or no GVHD Responses	2 Participants

SECONDARY outcome

Timeframe: Day 90

Population: Six subjects expired prior to day 90.

Number of subjects exhibiting any progression requiring re-escalation of steroid dosing or initiation of additional topical or systemic therapy after achieving an initial complete or partial response prior to Day 90.

Outcome measures

Outcome measures
Measure	Tocilizumab n=7 Participants Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks.
GVHD Flares	1 Participants

SECONDARY outcome

Timeframe: Day 56, Day 180 and Day 365

Population: Six subjects expired prior to day 56.

Number of subjects for whom immunosuppressive therapy (corticosteroid, cyclosporine, tacrolimus, sirolimus, etc.) was discontinued. This will be evaluated at Day 56, Day 180 and Day 365.

Outcome measures

Outcome measures
Measure	Tocilizumab n=7 Participants Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks.
Discontinuation of Immunosuppression Day 56	0 Participants
Discontinuation of Immunosuppression Day 180	0 Participants
Discontinuation of Immunosuppression Day 365	1 Participants

SECONDARY outcome

Timeframe: 1 year

Population: For this analysis, all thirteen subjects meeting eligibility criteria were included.

Number of subjects alive at one year.

Outcome measures

Outcome measures
Measure	Tocilizumab n=13 Participants Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks.
Overall Survival	3 Participants

SECONDARY outcome

Timeframe: Day 56

Population: Six subjects expired prior to day 56.

Number of subjects experiencing at least one serious adverse event or adverse event of CTCAE grade 3, 4, or 5 at Day 56 following the initiation of tocilizumab therapy.

Outcome measures

Outcome measures
Measure	Tocilizumab n=7 Participants Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks.
Number of Subjects Experiencing at Least One Serious Adverse Event or Grade 3 Non-serious Adverse Event	7 Participants

SECONDARY outcome

Timeframe: 6 and 12 months

Population: For this analysis, all thirteen participants originally meeting eligibility criteria were included for evaluation of survival status. Living patients were evaluated for symptoms.

Number of subjects alive and not experiencing GVHD signs or symptoms at 6 and 12 months. At the six month time point, seven subjects had expired. At the 12 month time point, 10 subjects had expired.

Outcome measures

Outcome measures
Measure	Tocilizumab n=13 Participants Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks.
Disease-free Survival 6 Month Timepoint	4 Participants
Disease-free Survival 12 Month Timepoint	3 Participants

SECONDARY outcome

Timeframe: 6 months

Population: All thirteen subjects meeting the initial eligibility criteria were included for evaluation of survival status and cause of death.

Number of subjects expiring from causes other than relapse of GVHD disease.

Outcome measures

Outcome measures
Measure	Tocilizumab n=13 Participants Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks. Patients with documented responses will continue to receive treatment at 8 mg/kg once every 3 weeks for at least two months (day 56). Patients that have some degree of response but without complete resolution of signs and symptoms of acute GVHD may continue to receive 8 mg/kg on a 3-week cycle until complete response is achieved or lack of further improvement. In patients who are beyond day 56 and whose GVHD has resolved, the dose of Tocilizumab will be reduced to 4 mg/kg every 3 weeks.
Non-relapse Mortality	8 Participants

Adverse Events

Tocilizumab

Serious events: 13 serious events

Other events: 0 other events

Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure	Tocilizumab n=13 participants at risk Drug: Tocilizumab Other Names: Actemra Tocilizumab will be administered intravenously at a dose of 8 mg/kg once every three weeks for three doses. After Day 56 doses may be decreased to 4mg/kg once every three weeks depending on GVHD response.
Investigations Elevated alanine aminotransferase Grade 3	7.7% 1/13 • Number of events 1 • An average of one year.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome Grade 5	7.7% 1/13 • Number of events 1 • An average of one year.
Gastrointestinal disorders Diarrhea Grade 3	7.7% 1/13 • Number of events 1 • An average of one year.
Gastrointestinal disorders Diarrhea Grade 4	7.7% 1/13 • Number of events 1 • An average of one year.
Infections and infestations Sepsis Grade 5	23.1% 3/13 • Number of events 3 • An average of one year.
Infections and infestations Sepsis Grade 4	23.1% 3/13 • Number of events 3 • An average of one year.
Nervous system disorders Presyncope Grade 1	7.7% 1/13 • Number of events 1 • An average of one year.
Infections and infestations Bronchial infection Grade 3	7.7% 1/13 • Number of events 1 • An average of one year.
Gastrointestinal disorders Enterocolitis Grade 3	7.7% 1/13 • Number of events 1 • An average of one year.
Respiratory, thoracic and mediastinal disorders Pneumothorax Grade 3	7.7% 1/13 • Number of events 1 • An average of one year.
Respiratory, thoracic and mediastinal disorders Respiratory failure Grade 4	7.7% 1/13 • Number of events 1 • An average of one year.
General disorders Multi-organ failure Grade 5	7.7% 1/13 • Number of events 1 • An average of one year.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other Grade 5	7.7% 1/13 • Number of events 1 • An average of one year.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome Grade 4	7.7% 1/13 • Number of events 1 • An average of one year.

Other adverse events

Adverse event data not reported

Additional Information

William R. Drobyski

Medical College of Wisconsin

Phone: 414-456-4941

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place