Trial Outcomes & Findings for Multicenter Study Of Natalizumab Plus Standard Steroid Treatment For High Risk Acute Graft-Versus-Host Disease (NCT NCT02133924)
NCT ID: NCT02133924
Last Updated: 2022-10-21
Results Overview
The primary endpoint for this clinical study is the proportion of complete response, CR (that is, the percent of patients with skin, liver, and GI GVHD - all stage 0) at day 28 of study treatment. Stage 0 = no rash, total bilirubin \<2 mg/dl, diarrhea \<500 ml/d
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
76 participants
Primary outcome timeframe
Day 28
Results posted on
2022-10-21
Participant Flow
Enrollment from 8/11/2016 -11/20/2020
Participant milestones
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
For participants whose Graft-Versus-Host Disease (GVHD) assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Overall Study
STARTED
|
76
|
|
Overall Study
COMPLETED
|
34
|
|
Overall Study
NOT COMPLETED
|
42
|
Reasons for withdrawal
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
For participants whose Graft-Versus-Host Disease (GVHD) assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Overall Study
Death
|
38
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
Baseline Characteristics
Multicenter Study Of Natalizumab Plus Standard Steroid Treatment For High Risk Acute Graft-Versus-Host Disease
Baseline characteristics by cohort
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=76 Participants
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
GVHD Prophylaxis
Other
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
59 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
64 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 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
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
61 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Diagnosis
Acute Leukemia
|
37 Participants
n=5 Participants
|
|
Diagnosis
MDS/MPN/CMML
|
25 Participants
n=5 Participants
|
|
Diagnosis
Lymphoma/CLL
|
8 Participants
n=5 Participants
|
|
Diagnosis
Multiple Myeloma
|
2 Participants
n=5 Participants
|
|
Diagnosis
Non-Malignant
|
4 Participants
n=5 Participants
|
|
Donor
Matched related
|
23 Participants
n=5 Participants
|
|
Donor
Matched unrelated
|
39 Participants
n=5 Participants
|
|
Donor
Mismatched related
|
8 Participants
n=5 Participants
|
|
Donor
Mismatched unrelated
|
6 Participants
n=5 Participants
|
|
Conditioning Regimen
Full
|
32 Participants
n=5 Participants
|
|
Conditioning Regimen
Reduced
|
44 Participants
n=5 Participants
|
|
Anti-thymocyte Globulin (ATG)
Yes
|
7 Participants
n=5 Participants
|
|
Anti-thymocyte Globulin (ATG)
No
|
69 Participants
n=5 Participants
|
|
GVHD Prophylaxis
CNI/MTX (+/- Other)
|
47 Participants
n=5 Participants
|
|
GVHD Prophylaxis
CNI/MMF (+/- Other)
|
7 Participants
n=5 Participants
|
|
GVHD Prophylaxis
CNI/sirolimus
|
5 Participants
n=5 Participants
|
|
GVHD Prophylaxis
Cyclophosphamide based
|
10 Participants
n=5 Participants
|
|
GVHD Prophylaxis
T Cell Depletion
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 28Population: one participant data inevaluable
The primary endpoint for this clinical study is the proportion of complete response, CR (that is, the percent of patients with skin, liver, and GI GVHD - all stage 0) at day 28 of study treatment. Stage 0 = no rash, total bilirubin \<2 mg/dl, diarrhea \<500 ml/d
Outcome measures
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 Participants
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Number of Participants With Complete Response (CR)
|
34 Participants
|
SECONDARY outcome
Timeframe: 1 yearPopulation: one participant data inevaluable
Number of participants with overall survival at 1 year
Outcome measures
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 Participants
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Number of Participants With Overall Survival (OS)
|
37 Participants
|
SECONDARY outcome
Timeframe: 6 months and 1 yearPopulation: one participant data inevaluable
Number of participants with Non-Relapse Mortality (NRM) at 6 months and 1 year
Outcome measures
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 Participants
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Number of Participants With Non-Relapse Mortality (NRM)
6 months
|
25 Participants
|
|
Number of Participants With Non-Relapse Mortality (NRM)
1 year
|
28 Participants
|
SECONDARY outcome
Timeframe: 1 yearPopulation: one participant data inevaluable
Number of participants with steroid-refractory (SR) GVHD to express cumulative incidence of treatment-refractory GVHD (defined as absence of CR or PR on day 28 of treatment or who receive additional immunosuppression prior to day 28)
Outcome measures
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 Participants
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Number of Participants With SR GVHD
|
30 Participants
|
SECONDARY outcome
Timeframe: up to 365 daysPopulation: one participant data inevaluable
Time in days to discontinuation of steroid therapy.
Outcome measures
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 Participants
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Time to Discontinuation of Steroid Therapy
|
108 days
Interval 30.0 to 365.0
|
SECONDARY outcome
Timeframe: 1 yearPopulation: one participant data inevaluable
Number of participants who received additional GVHD therapies (defined as the initiation of a new acute GVHD therapy, regardless of duration)
Outcome measures
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 Participants
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Number of Participants Who Received Additional GVHD Therapies
|
33 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: one participant data inevaluable
Number of serious infections (defined as score 3 by the Blood and Marrow Transplant Clinical Trials Network)
Outcome measures
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 Participants
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Number of Serious Infections
|
52 events
|
SECONDARY outcome
Timeframe: Day 28Population: one participant data inevaluable
Overall response rate (CR + PR) at day 28. Partial Response (PR) is defined as improvement in one or more organs involved with GVHD symptoms without progression in others. For a response to be scored as PR on day 28, the patient must be in PR on day 28 and have had no intervening non-study therapy for acute GVHD.
Outcome measures
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 Participants
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Number of Participants With Overall Response Rate (CR + PR)
|
45 Participants
|
Adverse Events
Participants With High Risk Acute Graft-Versus-Host Disease
Serious events: 51 serious events
Other events: 32 other events
Deaths: 38 deaths
Serious adverse events
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 participants at risk
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Hepatobiliary disorders
Acute Liver Injury
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Immune system disorders
GVHD
|
34.7%
26/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
General disorders
Fatigue
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Cardiac disorders
Atrial Fibrillation
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Nervous system disorders
Autonomic Disorder
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Renal and urinary disorders
Depression
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Immune system disorders
Autoimmune Encephalitis
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Gastrointestinal disorders
GI Hemorrhage
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Gastrointestinal disorders
Diarrhea
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Blood and lymphatic system disorders
Graft Failure
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Blood and lymphatic system disorders
Hemolytic Anemia
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Vascular disorders
Hypotension
|
4.0%
3/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Psychiatric disorders
Psychosis
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment Related Secondary Malignancy (PTLD)
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Relapse
|
9.3%
7/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Vascular disorders
Thrombotic Microangiopathy
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Hepatobiliary disorders
Transaminitis
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Blood and lymphatic system disorders
Poor Graft Function
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Sepsis
|
18.7%
14/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Lung Infection
|
6.7%
5/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Encephalitis Infection
|
4.0%
3/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Meningitis
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Bacteremia
|
8.0%
6/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
C. Difficile Infection
|
5.3%
4/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Urinary Track Infection
|
4.0%
3/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Sinusitis
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Viremia
|
5.3%
4/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Immune system disorders
Upper Respiratory Infection
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Fungemia
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Duodenal Infection
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
EBV PTLD
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Small Intestine Infection
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
CNS Toxoplasmosis
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Mucormycosis
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Invasive fungal Infection: Aspergillus Galactomannan
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
Other adverse events
| Measure |
Participants With High Risk Acute Graft-Versus-Host Disease
n=75 participants at risk
For participants whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) 2mg/kg/d (or methyl-prednisolone IV equivalent) and Natalizumab 300mg on days 0 and 14.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
14.7%
11/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Psychiatric disorders
Anxiety
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Vascular disorders
Hypertension
|
4.0%
3/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Psychiatric disorders
Delirium
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
General disorders
Edema
|
8.0%
6/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Gastrointestinal disorders
GI Hemorrhage
|
4.0%
3/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Immune system disorders
GVHD
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Renal and urinary disorders
Hematuria
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Blood and lymphatic system disorders
Hemolytic Anemia
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Investigations
Blood Bilirubin Increased
|
5.3%
4/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
8.0%
6/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
5.3%
4/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Metabolism and nutrition disorders
Hypokalemia
|
4.0%
3/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Vascular disorders
Hypotension
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Investigations
White Blood Cell Decreased
|
14.7%
11/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Investigations
Lymphocyte Count Decreased
|
10.7%
8/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Investigations
Neutrophil Count Decreased
|
4.0%
3/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Nervous system disorders
Somnolence
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Investigations
Platelet Count Decreased
|
22.7%
17/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Vascular disorders
Thrombotic Microangiopathy
|
5.3%
4/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
General disorders
Fatigue
|
6.7%
5/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Musculoskeletal and connective tissue disorders
Generalized Muscle Weakness
|
4.0%
3/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness Lower Limb
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Catheter Related Infection
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Colitis
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
CMV Viremia
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Skin Infection
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Investigations
Alanine Aminotransferase Increased
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Investigations
Alkaline Phosphatase Increased
|
2.7%
2/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Investigations
Aspartate Aminotransferase Increased
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Metabolism and nutrition disorders
Hyponatremia
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
|
Infections and infestations
Lung Infection
|
1.3%
1/75 • 1 year
one participant withdrew and was inevaluable for AEs
|
Additional Information
Dr. John Levine
Icahn School of Medicine at Mount Sinai
Phone: 212-241-3429
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60