Trial Outcomes & Findings for Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia (NCT NCT02224872)
NCT ID: NCT02224872
Last Updated: 2023-03-10
Results Overview
Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
18 participants
Primary outcome timeframe
1 year
Results posted on
2023-03-10
Participant Flow
Participant milestones
| Measure |
Bone Marrow Transplant
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
16
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia
Baseline characteristics by cohort
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Age, Categorical
<=18 years
|
5 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=99 Participants
|
|
Age, Continuous
|
30 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
18 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 1 yearFeasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).
Outcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?
|
18 Participants
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Number of Patients That Have Survived at One Year
|
18 Participants
|
SECONDARY outcome
Timeframe: 60 daysDonor chimerism will be measured in the peripheral blood around day 30 and day 60. Patients with \>5% donor chimerism around day 60 will be considered as having engrafted.
Outcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant
|
7 Participants
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant
|
0 Participants
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Number of Participants With Major Toxicities Related to Transplant
|
0 Participants
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Number of Patients That Expired Due to Transplant Related Mortality
|
0 Participants
|
SECONDARY outcome
Timeframe: 1 yearGraft failure: \< 5% donor chimerism in blood and/or bone marrow on \~Day 30 or after and on all subsequent measurements. Primary graft failure: \< 5% donor chimerism in blood and/or bone marrow by \~ Day 56 Secondary graft failure: achievement of \> 5% donor chimerism, followed by sustained \<5% donor chimerism in blood and/or bone marrow.
Outcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Number of Patients With Primary or Secondary Graft Failure Following Transplant
|
17 Participants
|
SECONDARY outcome
Timeframe: 1 yearParticipants were graded during clinical visits based on evidence and extent of skin rash, liver involvement, and GI tract involvement
Outcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Number of Participants With Grade II-IV or Grade III-IV Acute GVHD
|
17 Participants
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Participants With Chronic GVHD at One Year
|
3 Participants
|
SECONDARY outcome
Timeframe: 1 yearCBC drawn daily with a WBC differential once the total WBC is greater than 100 until ANC \> 500 for three days or two consecutive measurements over a three day period; then CBC drawn weekly with differential.
Outcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant
|
18.85 days
Interval 14.0 to 48.0
|
SECONDARY outcome
Timeframe: 1 yearOutcome measures
| Measure |
Bone Marrow Transplant
n=18 Participants
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Participants That Were GVHD Free, Relapse Free Survival (GRFS)
|
14 Participants
|
Adverse Events
Bone Marrow Transplant
Serious events: 7 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bone Marrow Transplant
n=18 participants at risk
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
Bone marrow transplant: Day 0
Thymoglobulin: 0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
Fludarabine: 30 mg/M2 IV on days -6 to -2
Cyclophosphamide: 14.5 mg/kg IV on days -6, -5, 3, 4
TBI: 200 cGy on day -1
Mesna: 40 mg/kg IV on days 3, 4
Tacrolimus: For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
Mycophenolic acid mofetil: 15 mg/kg PO/IV TID beginning on day 5 through day 35
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrom
|
5.6%
1/18 • Number of events 1 • Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
|
|
Respiratory, thoracic and mediastinal disorders
Acute Hypoxic Respiratory Failure
|
5.6%
1/18 • Number of events 1 • Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
|
|
Vascular disorders
Intracranial Hemorrhage
|
5.6%
1/18 • Number of events 1 • Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
|
|
Vascular disorders
Retroperitoneal Hemorrhage
|
5.6%
1/18 • Number of events 1 • Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
|
|
Vascular disorders
Hemorrhagic Shock
|
5.6%
1/18 • Number of events 1 • Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
1/18 • Number of events 2 • Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.6%
1/18 • Number of events 1 • Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
|
|
Infections and infestations
Persistent Fevers
|
5.6%
1/18 • Number of events 1 • Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
|
|
Renal and urinary disorders
dysuria/hematuria
|
5.6%
1/18 • Number of events 1 • Adverse event data will be collected from day 0 of transplant through day 60 post transplant. All-Cause mortality is reported up to one year after transplant
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place