Trial Outcomes & Findings for Itacitinib for Low Risk GVHD (NCT NCT03846479)
NCT ID: NCT03846479
Last Updated: 2023-02-06
Results Overview
Number of patients who achieve CR or PR by day 28 of treatment with itacitinib without the addition of any other systemic GVHD treatment including steroids. Complete Response (CR): All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR on day 28, the patient must be in CR on that day and have had no intervening additional GVHD therapy. Partial Response (PR): An improvement in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR on day 28, the patient must be in PR on that day and have had no intervening additional GVHD therapy.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
70 participants
Primary outcome timeframe
Day 28
Results posted on
2023-02-06
Participant Flow
Participant milestones
| Measure |
Low Risk GVHD Patients Treated
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Overall Study
STARTED
|
70
|
|
Overall Study
COMPLETED
|
61
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
Low Risk GVHD Patients Treated
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Overall Study
Death
|
8
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Itacitinib for Low Risk GVHD
Baseline characteristics by cohort
| Measure |
Low Risk GVHD Patients Treated
n=70 Participants
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Age, Continuous
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
59 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
4 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
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
57 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Diagnosis
Acute Leukemia
|
32 Participants
n=5 Participants
|
|
Diagnosis
MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm (MDS/MPN)
|
29 Participants
n=5 Participants
|
|
Diagnosis
Lymphoma
|
6 Participants
n=5 Participants
|
|
Diagnosis
Non-Malignant
|
3 Participants
n=5 Participants
|
|
Donor
Matched related
|
13 Participants
n=5 Participants
|
|
Donor
Matched unrelated
|
37 Participants
n=5 Participants
|
|
Donor
Mismatched related
|
15 Participants
n=5 Participants
|
|
Donor
Mismatched unrelated
|
5 Participants
n=5 Participants
|
|
Conditioning Regimen
Myeloablative
|
33 Participants
n=5 Participants
|
|
Conditioning Regimen
Reduced/Non-Myeloablative
|
37 Participants
n=5 Participants
|
|
Anti-Thymocyte Globulin (ATG)
Yes
|
9 Participants
n=5 Participants
|
|
Anti-Thymocyte Globulin (ATG)
No
|
61 Participants
n=5 Participants
|
|
GVHD Prophylaxis
CNI/MTX (+/- Other)
|
24 Participants
n=5 Participants
|
|
GVHD Prophylaxis
CNI/MMF (+/- Other)
|
7 Participants
n=5 Participants
|
|
GVHD Prophylaxis
CNI/sirolimus
|
2 Participants
n=5 Participants
|
|
GVHD Prophylaxis
Cyclophosphamide based
|
35 Participants
n=5 Participants
|
|
GVHD Prophylaxis
T Cell Depletion
|
2 Participants
n=5 Participants
|
|
GVHD Prophylaxis
Other
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 28Number of patients who achieve CR or PR by day 28 of treatment with itacitinib without the addition of any other systemic GVHD treatment including steroids. Complete Response (CR): All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR on day 28, the patient must be in CR on that day and have had no intervening additional GVHD therapy. Partial Response (PR): An improvement in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR on day 28, the patient must be in PR on that day and have had no intervening additional GVHD therapy.
Outcome measures
| Measure |
Low Risk GVHD Patients Treated
n=70 Participants
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Number of Patients Who Achieve CR or PR by Day 28 of Treatment
|
62 Participants
|
PRIMARY outcome
Timeframe: Day 28Number of participants who developed steroid refractory GVHD within 28 days of starting steroids. Steroid-refractory GVHD (defined as GVHD that worsens (increase by one or more grade) after 3 days, or fails to respond to treatment within 7 days (for GVHD grade III) or 14 days (for GVHD grade II) or 2nd line therapy beyond systemic steroid treatment is begun within 28 days of starting steroids.
Outcome measures
| Measure |
Low Risk GVHD Patients Treated
n=70 Participants
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Number of Participants Who Developed Steroid Refractory GVHD
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 90Number of participants who developed serious infections by day 90. Serious infectious complications is defined as any viral and bacterial infections requiring treatment and proven fungal infections.
Outcome measures
| Measure |
Low Risk GVHD Patients Treated
n=70 Participants
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Number of Participants With Serious Infectious
|
19 Participants
|
SECONDARY outcome
Timeframe: 6 months and 1 yearNumber of overall survival (OS), defined as the duration from the date of diagnosis to death or last follow-up, with no restriction on the cause of death.
Outcome measures
| Measure |
Low Risk GVHD Patients Treated
n=70 Participants
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Number of Participants Alive at 6 Months and 1 Year
6 months
|
66 Participants
|
|
Number of Participants Alive at 6 Months and 1 Year
1 year
|
62 Participants
|
SECONDARY outcome
Timeframe: 6 months and 1 yearNumber of participants with non-relapse mortality (NRM) at 6 months and 1 year
Outcome measures
| Measure |
Low Risk GVHD Patients Treated
n=70 Participants
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Number of Participants With Non-relapse Mortality (NRM)
6 months
|
2 Participants
|
|
Number of Participants With Non-relapse Mortality (NRM)
1 year
|
3 Participants
|
SECONDARY outcome
Timeframe: 6 months and 1 yearNumber of participants who relapsed by 6 months and by 1 year
Outcome measures
| Measure |
Low Risk GVHD Patients Treated
n=70 Participants
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Number of Participants Who Relapsed
6 months
|
8 Participants
|
|
Number of Participants Who Relapsed
1 year
|
12 Participants
|
SECONDARY outcome
Timeframe: 1 yearNumber of participants who developed chronic GVHD requiring systemic treatment at 1 year
Outcome measures
| Measure |
Low Risk GVHD Patients Treated
n=70 Participants
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Number of Participants Who Developed Chronic GVHD
|
18 Participants
|
SECONDARY outcome
Timeframe: Day 28Cumulative steroid dose (over 4 weeks) in patients who receive steroids as second line therapy
Outcome measures
| Measure |
Low Risk GVHD Patients Treated
n=70 Participants
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Cumulative Steroid Dose
|
1.9 mg/kg
Standard Error 0.6
|
Adverse Events
Low Risk GVHD Patients Treated
Serious events: 23 serious events
Other events: 34 other events
Deaths: 8 deaths
Serious adverse events
| Measure |
Low Risk GVHD Patients Treated
n=70 participants at risk
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
General disorders
Fever
|
4.3%
3/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Renal and urinary disorders
Dysuria
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Injury, poisoning and procedural complications
Subarachnoid Hemorrhage
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
Adenovirus Hemorrhagic Cystitis
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Renal and urinary disorders
Acute Kidney Injury
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Nervous system disorders
Syncope
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Gastrointestinal disorders
Vomiting
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Immune system disorders
GVHD
|
5.7%
4/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Investigations
Blood Bilirubin Increased
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Vascular disorders
Hypertension
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Relapse
|
7.1%
5/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
C. Difficile Infection
|
4.3%
3/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
SARS-CoV-2 Infection
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
EBV Infection
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
BK Cystitis
|
2.9%
2/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
Sepsis
|
4.3%
3/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
Catheter Related Infection
|
5.7%
4/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
Bacteremia
|
2.9%
2/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
Upper Respiratory Infection
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
Lung Infection
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
CMV Viremia
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
2.9%
2/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Psychiatric disorders
Suicidal Ideation
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Injury, poisoning and procedural complications
Fall
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
Other adverse events
| Measure |
Low Risk GVHD Patients Treated
n=70 participants at risk
Itacitinib 200 mg administered orally daily for 28 days, with a second 28 day cycle allowed for responding patients.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
20.0%
14/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Nervous system disorders
Syncope
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Vascular disorders
Hypertension
|
4.3%
3/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Metabolism and nutrition disorders
Hypokalemia
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Vascular disorders
Hypotension
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Investigations
White Blood Cell Decreased
|
15.7%
11/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Investigations
Lymphocyte Count Decreased
|
2.9%
2/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Investigations
Neutrophil Count Decreased
|
15.7%
11/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Nervous system disorders
Reversible Posterior Leukoencephalopathy Syndrome
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Investigations
Platelet Count Decreased
|
18.6%
13/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Vascular disorders
Thrombotic Microangiopathy
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Nervous system disorders
Headache
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Investigations
Alanine Aminotransferase Increased
|
7.1%
5/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
Urinary Tract Infection
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
CMV Infection
|
4.3%
3/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
EBV Infection
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Infections and infestations
Multifocal Pneumonia
|
1.4%
1/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
|
Musculoskeletal and connective tissue disorders
Arthralgia and/or Myalgia
|
2.9%
2/70 • 90 days for Adverse Events 1 year for All-Cause Mortality
|
Additional Information
Dr. John Levine
Icahn School of Medicine at Mount Sinai
Phone: 212-241-6021
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60