Graft Vs Host Disease, Graft-versus-host-disease, Acute-graft-versus-host Disease, Prevention of aGVHD
Conditions
Brief summary
This Phase II open label study will evaluate the safety and efficacy of repeat doses of RGI-2001 in combination with standard of care treatment for the prevention of acute graft-vs-host-disease (aGvHD) in subjects following Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT). These subjects will be compared to contemporary controls.
Detailed description
This is an open-label, multi-center, single-arm study to evaluate six weekly doses of RGI-2001 in combination with standard of care treatment for the prevention of aGvHD in subjects following alloHSCT. The study will include a Safety Run-in Phase to assess the safety and tolerability of 6 weekly doses of RGI-2001 followed by an Expansion Phase in which the potential efficacy of 6 weekly doses of RGI-2001 in addition to standard of care for GvHD prophylaxis will be assessed. Comparison will be made to a contemporaneous control group.
Interventions
DRUGRGI-2001
Subjects will receive 6 weekly doses of RGI 2001, 100 μg/kg via IV administration after completion of alloHSCT
DRUGStandard of Care
Standard of care prophylaxis regimen will be administered according to institutional guidelines
Sponsors
Regimmune Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Ages ≥ 18 and ≤ 65 years of age 2. Has a hematologic malignancy which includes Acute myelogenous leukemia (AML), T or B cell acute lymphoblastic leukemia (ALL) Myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), myeloproliferative disorder (MPD) including myeloid metaplasia and CML 3. Must have adequate organ function 4. Transplant Donor: Matched related donor or Unrelated donor 5. Is a candidate for anti-graft-vs-host-disease (GvHD) prophylaxis that includes a calcineurin inhibitor 6. Ability to understand and willingness to sign a written informed consent form 7. If female of childbearing potential, must have had a negative serum pregnancy test prior to enrollment and must have agreed to use a double barrier method of contraception for 30 days after RGI-2001 administration 8. If male, must be sterile or willing to use an approved method of contraception from the time of informed consent to 90 days after last dose of RGI-2001 administration
Exclusion criteria
1. Has had any other prior organ transplantation 2. Planned procedure to deplete regulatory T cells from donor transplant materials 3. Planned reduced intensity conditioning 4. Has had prior treatment with anti-CD3, other T cell depleting antibodies, or anti-thymocyte globulin within 12 months prior to alloHSCT procedure 5. Has progressive underlying malignant disease including post-transplant lymphoproliferative disease 6. Has evidence of active central nervous system (CNS) disease including known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of CNS involvement) 7. Is female and pregnant or lactating 8. Has a documented history of uncontrolled autoimmune disease or on active treatment 9. History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to receiving study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grades II-IV aGVHD | Day 100 post-transplant | Acute GVHD will be graded and assessed according to modified KEYSTONE criteria and the severity grade (Grade II through IV) were captured up through the first 100 days post-transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Grades II-IV aGVHD | Day 180 post-transplant | Acute GVHD will be graded and assessed within 180 days post-transplant |
| Non-relapse Mortality (NRM) Rates | 1 year post-transplant | The probability of mortality not preceded by relapse of the underlying malignancy will be estimated |
| Disease-free Survival (DFS) | 1 year post-transplant | The probability of survival without relapse of the underlying malignancy will be estimated |
| GvHD-free, Relapse Free Survival (GRFS) | 1 year post-transplant | The probability of survival without relapse of the underlying malignancy, without severe (grades 3-4) acute GVHD, and without chronic GVHD requiring systemic immunosuppression will be estimated |
| Overall Survival (OS) | 1 year post-transplant | The probability of survival will be estimated |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RGI-2001 Subjects will be administered RGI 2001 in combination with standard of care treatment
RGI-2001: Subjects will receive 6 weekly doses of RGI 2001, 100 μg/kg via IV administration after completion of alloHSCT
Standard of Care: Standard of care prophylaxis regimen will be administered according to institutional guidelines | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | RGI-2001 |
|---|---|
| Age, Continuous | 48.7 years STANDARD_DEVIATION 11.89 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 45 Participants |
| Region of Enrollment United States | 49 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 49 |
| other Total, other adverse events | 49 / 49 |
| serious Total, serious adverse events | 8 / 49 |
Outcome results
Primary
Grades II-IV aGVHD
Acute GVHD will be graded and assessed according to modified KEYSTONE criteria and the severity grade (Grade II through IV) were captured up through the first 100 days post-transplant
Time frame: Day 100 post-transplant
Population: intent to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RGI-2001 | Grades II-IV aGVHD | 11 Participants |
Secondary
Disease-free Survival (DFS)
The probability of survival without relapse of the underlying malignancy will be estimated
Time frame: 1 year post-transplant
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RGI-2001 | Disease-free Survival (DFS) | 40 Participants |
Secondary
Grades II-IV aGVHD
Acute GVHD will be graded and assessed within 180 days post-transplant
Time frame: Day 180 post-transplant
Population: Intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RGI-2001 | Grades II-IV aGVHD | 11 Participants |
Secondary
GvHD-free, Relapse Free Survival (GRFS)
The probability of survival without relapse of the underlying malignancy, without severe (grades 3-4) acute GVHD, and without chronic GVHD requiring systemic immunosuppression will be estimated
Time frame: 1 year post-transplant
Population: intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RGI-2001 | GvHD-free, Relapse Free Survival (GRFS) | 26 Participants |
Secondary
Non-relapse Mortality (NRM) Rates
The probability of mortality not preceded by relapse of the underlying malignancy will be estimated
Time frame: 1 year post-transplant
Population: intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RGI-2001 | Non-relapse Mortality (NRM) Rates | 2 Participants |
Secondary
Overall Survival (OS)
The probability of survival will be estimated
Time frame: 1 year post-transplant
Population: intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RGI-2001 | Overall Survival (OS) | 44 Participants |