Chronic Graft Versus Host Disease
Conditions
Keywords
Graft vs. Host Disease, GVHD, chronic graft versus host disease (cGVHD), Allogeneic Transplant, Ofatumumab
Brief summary
To study the safety and side effects of Ofatumumab in the treatment of chronic graft-versus-host disease (GvHD). This study will also evaluate effectiveness of Ofatumumab when added to standard steroid treatment for chronic graft-versus-host disease
Detailed description
This is a phase I-II trial to examine the safety and efficacy of prednisone and escalating dose of ofatumumab for the primary therapy of chronic GVHD.
Interventions
DRUGOfatumumab
Phase I: test an escalating dose of ofatumumab at cohorts of 300 mg, 700 mg, and 1000 mg given on day 0 and 14 of study. Phase II: Ofatumumab MTD on day 0 and 14; patients will be followed for total of 24 months (months 1, 3, 6, 12 after therapy, then at 18 and 24 months following therapy)
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hematopoietic cell transplantation (HCT) recipients newly requiring systemic glucocorticoid therapy (at ≥ 1mg/kg/day prednisone or equivalent) for chronic GVHD * Participants can be enrolled and begin study therapy with ofatumumab within 14 days from initiation of 1 mg/kg/day prednisone for therapy of chronic GVHD.
Exclusion criteria
* Relapse of primary hematologic malignancy that served as indication for HCT. * Previous systemic glucocorticoid therapy (at ≥ 1mg/kg/day prednisone or equivalent) for chronic GVHD * Prior systemic glucocorticoid therapy for acute GVHD is permitted * Prior or ongoing systemic immune suppressive agents (including, but not limited to common examples such as calcineurin inhibitors, sirolimus, mycophenolate mofetil) provided for either prevention or treatment of acute GVHD are permitted and part of routine standard of care * Current active hepatic or biliary disease (with exception of liver disease secondary to chronic GVHD, or patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment). * Patients with abnormal liver function tests due to chronic GVHD are specifically not excluded from the study. This is a common manifestation of chronic GVHD, and thus a major target for the study therapy. * Treatment with experimental non-FDA approved therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer * Other past or current solid tumor malignancy * Have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. * Prior treatment with anti-cluster of differentiation antigen 20 (CD20) monoclonal antibody or alemtuzumab within 3 months prior to start of therapy. * Uncontrolled infectious complications not responsive to appropriate antimicrobial therapy. * History of significant cerebrovascular disease (i.e. stroke or TIA) in the past 6 months or ongoing event with active symptoms or sequelae * HIV positivity * Uncontrolled, current significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. * A history of cardiac disease, such as coronary disease, arrhythmia or congestive heart failure that are on appropriate medical therapy and without evidence of current decompensation are eligible. * Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient. * Those patients with medical conditions that are controlled with medical therapy are eligible. * Clinically active Hepatitis B defined as positive HBsAg; or positive HBcAb with detectable hepatitis B virus (HBV) DNA viral load. Patients who are HBcAb with undetectable HBV DNA viremia are eligible. * Positive serology for hepatitis C (HC) defined as a positive test and confirmed by HC recombinant immunoblot assay (RIBA) or hepatitis C virus (HCV) RNA viral load * Screening laboratory value
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose of Ofatumumab | within 21 days of initiation | Maximum Tolerated Dose was determined by increasing doses, beginning at 300 mg on day 0 and day 14, then increasing to 700 mg on day 0 and day 14 and finally 1000 mg on day 0 and day 14. |
| Participants Response Rates | 6 months following initiation of Ofatumumab | Overall response rate (ORR) at 6 months following initiation of therapy. ORR is the composite outcome of complete response and partial response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) at 24 Months | Up to 24 months | Overall Survival is defined as the time period from start of treatment to death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Cohort 1: Ofatumumab Phase I Cohort 1: dose of ofatumumab at 300 mg given on day 0 and 14 of study. | 3 |
| Phase 1 Cohort 2: Ofatumumab Phase I Cohort 2: dose of ofatumumab at 700 mg given on day 0 and 14 of study. | 3 |
| Phase 1 Cohort 3: Ofatumumab Phase I Cohort 3: dose of ofatumumab at 1000 mg given on day 0 and 14 of study. | 6 |
| Phase 2: Maximum Tolerated Dose of Ofatumumab Phase II: Maximum tolerated dose (MTD) of Ofatumumab
Ofatumumab at 1000 mg on day 0 and 14 | 32 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 6 |
Baseline characteristics
| Characteristic | Phase 1 Cohort 1: Ofatumumab | Phase 1 Cohort 2: Ofatumumab | Phase 1 Cohort 3: Ofatumumab | Phase 2: Maximum Tolerated Dose of Ofatumumab | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 2 Participants | 10 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 4 Participants | 22 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants | 29 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 6 Participants | 30 Participants | 42 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 6 participants | 32 participants | 44 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants | 10 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants | 22 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 1 / 3 | 3 / 6 | 9 / 32 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 24 / 32 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 4 / 6 | 25 / 32 |
Outcome results
Primary
Maximum Tolerated Dose of Ofatumumab
Maximum Tolerated Dose was determined by increasing doses, beginning at 300 mg on day 0 and day 14, then increasing to 700 mg on day 0 and day 14 and finally 1000 mg on day 0 and day 14.
Time frame: within 21 days of initiation
Population: All participants in phase 1 portion of study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: All Participants | Maximum Tolerated Dose of Ofatumumab | 1000 mg |
Primary
Participants Response Rates
Overall response rate (ORR) at 6 months following initiation of therapy. ORR is the composite outcome of complete response and partial response
Time frame: 6 months following initiation of Ofatumumab
Population: Participants enrolled in Phase 2 portion of study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: All Participants | Participants Response Rates | 62.5 percentage of participants |
Secondary
Overall Survival (OS) at 24 Months
Overall Survival is defined as the time period from start of treatment to death.
Time frame: Up to 24 months
Population: Participants enrolled in Phase 2 portion of study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: All Participants | Overall Survival (OS) at 24 Months | 74.4 percentage of participants |