Trial Outcomes & Findings for PROACTIVE: Preventing Acute/Chronic GVHD With TocIlizumab Combined With GVHD Prophylaxis Post allogEneic Transplant (NCT NCT03699631)
NCT ID: NCT03699631
Last Updated: 2023-04-19
Results Overview
GRFS is defined as survival without grade III-IV acute graft versus host disease (GVHD), systemic therapy requiring chronic GVHD, relapse, or death at 12 months after matched related/unrelated donor bone marrow or peripheral blood allogeneic hematopoietic cell transplantation (alloHCT) using myeloablative conditioning (MAC). Patients who are alive without GVHD will be censored at the last follow-up.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
29 participants
Primary outcome timeframe
Day 365
Results posted on
2023-04-19
Participant Flow
Thirty-one subjects signed consent, but two did not meet final eligibility criteria and were not enrolled.
Participant milestones
| Measure |
Tacrolimus/Methotrexate/Tocilizumab
Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant.
Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11.
Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days).
Tacrolimus: Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion.
Tocilizumab: Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-allogeneic hematopoietic cell transplantation. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus.
|
|---|---|
|
Overall Study
STARTED
|
29
|
|
Overall Study
COMPLETED
|
26
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Tacrolimus/Methotrexate/Tocilizumab
Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant.
Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11.
Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days).
Tacrolimus: Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion.
Tocilizumab: Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-allogeneic hematopoietic cell transplantation. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
Baseline Characteristics
PROACTIVE: Preventing Acute/Chronic GVHD With TocIlizumab Combined With GVHD Prophylaxis Post allogEneic Transplant
Baseline characteristics by cohort
| Measure |
Tacrolimus/Methotrexate/Tocilizumab
n=29 Participants
Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant.
Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11.
Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days).
Tacrolimus: Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion.
Tocilizumab: Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-allogeneic hematopoietic cell transplantation. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
28 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
49.0 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
28 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
|
2 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
|
27 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
|
29 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 365GRFS is defined as survival without grade III-IV acute graft versus host disease (GVHD), systemic therapy requiring chronic GVHD, relapse, or death at 12 months after matched related/unrelated donor bone marrow or peripheral blood allogeneic hematopoietic cell transplantation (alloHCT) using myeloablative conditioning (MAC). Patients who are alive without GVHD will be censored at the last follow-up.
Outcome measures
| Measure |
Tacrolimus/Methotrexate/Tocilizumab
n=29 Participants
Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant.
Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11.
Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days).
Tacrolimus: Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion.
Tocilizumab: Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-alloHCT. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus.
|
|---|---|
|
The Number of Patients With GVHD/Relapse-free (GRFS) Survival
|
25 Participants
|
Adverse Events
Tacrolimus/Methotrexate/Tocilizumab
Serious events: 28 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tacrolimus/Methotrexate/Tocilizumab
n=29 participants at risk
Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant.
Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11.
Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days).
Tacrolimus: Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion.
Tocilizumab: Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-alloHCT. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Cardiac disorders
Heart Failure
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Cardiac disorders
Pericardial Tamponade
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Colitis
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
10.3%
3/29 • Number of events 3 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
General disorders
Fever
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Infections and infestations
Lung infection
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
Infections and infestations
Skin infection
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Fall
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Investigations
Blood bilirubin increased
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
3.4%
1/29 • Number of events 2 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Vascular disorders
Hematoman
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Vascular disorders
Hypotension
|
3.4%
1/29 • Number of events 1 • 1 year
|
Other adverse events
| Measure |
Tacrolimus/Methotrexate/Tocilizumab
n=29 participants at risk
Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant.
Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11.
Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days).
Tacrolimus: Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion.
Tocilizumab: Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-alloHCT. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
41.4%
12/29 • Number of events 15 • 1 year
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Eye disorders
Dry eye
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
Gastrointestinal disorders
Dry mouth
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Dyspepsia
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Mucositis oral
|
27.6%
8/29 • Number of events 9 • 1 year
|
|
Gastrointestinal disorders
Rectal pain
|
6.9%
2/29 • Number of events 3 • 1 year
|
|
General disorders
Edema limbs
|
6.9%
2/29 • Number of events 3 • 1 year
|
|
General disorders
General disorders - Other, specify
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Infections and infestations
Cytomegalovirus infection reactivation
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Infections and infestations
Infections and infestations - Other, specify
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Infections and infestations
Skin infection
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
41.4%
12/29 • Number of events 21 • 1 year
|
|
Investigations
Alkaline phosphatase increased
|
17.2%
5/29 • Number of events 5 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
41.4%
12/29 • Number of events 16 • 1 year
|
|
Investigations
Creatinine increased
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Investigations
Electrocardiogram QT corrected interval prolonged
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Investigations
Lymphocyte count decreased
|
13.8%
4/29 • Number of events 8 • 1 year
|
|
Investigations
Neutrophil count decreased
|
72.4%
21/29 • Number of events 61 • 1 year
|
|
Investigations
Platelet count decreased
|
89.7%
26/29 • Number of events 91 • 1 year
|
|
Investigations
White blood cell decreased
|
75.9%
22/29 • Number of events 58 • 1 year
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
3.4%
1/29 • Number of events 3 • 1 year
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
3.4%
1/29 • Number of events 3 • 1 year
|
|
Metabolism and nutrition disorders
Tumor lysis syndrome
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders - Other, pecify
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Nervous system disorders
Headache
|
10.3%
3/29 • Number of events 3 • 1 year
|
|
Nervous system disorders
Seizure
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
Acute kidney injury
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
6.9%
2/29 • Number of events 2 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
3.4%
1/29 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
10.3%
3/29 • Number of events 6 • 1 year
|
|
Vascular disorders
Hypertension
|
13.8%
4/29 • Number of events 4 • 1 year
|
|
Vascular disorders
Hypotension
|
3.4%
1/29 • Number of events 1 • 1 year
|
Additional Information
William Drobyski, MD
Froedtert and the Medical College of Wisconsin
Phone: 414-805-6700
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place