Trial Outcomes & Findings for NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia (NCT NCT02833805)

Results Overview

Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

1 year

Results posted on

2022-07-12

Participant Flow

Participant milestones

Participant milestones
Measure	Bone Marrow Transplant Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as graft-versus-host disease (GVHD) prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Overall Study STARTED	21
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Age, Categorical <=18 years	7 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	25 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 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	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race/Ethnicity, Customized African American	4 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	14 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants
Region of Enrollment United States	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Number of enrolled participants who receive BMT, achieve engraftment, and are alive at one year post bone marrow transplant (BMT).

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Overall Survival and Engraftment at One Year	19 Participants

SECONDARY outcome

Timeframe: 1 year

Number of participants alive at one year after BMT.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Overall Survival at One Year	19 Participants

SECONDARY outcome

Timeframe: 1 year

Probability of neutrophil recovery will be assessed by the number of participants who have recovered neutrophil counts at 1 year (\>500 ANC).

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Probability of Neutrophil Recovery as Assessed by the Number of Participants Who Have Recovered Neutrophil Counts	21 Participants

SECONDARY outcome

Timeframe: 1 year

Probability of platelet recovery will be assessed by the number of participants who have recovered platelet counts at 1 year.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Probability of Platelet Recovery as Assessed by Number of Participants Who Have Recovered Platelet Counts	20 Participants

SECONDARY outcome

Timeframe: 1 year

Number of participants who experience primary graft failure by one year after BMT.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Number of Participants Who Experience Primary Graft Failure	21 Participants

SECONDARY outcome

Timeframe: 1 year

Number of participants who experience secondary graft failure by one year after BMT.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Number of Participants Who Experience Secondary Graft Failure	19 Participants

SECONDARY outcome

Timeframe: Day 100

Number of participants who experience grade II, III, or IV acute GVHD by Day 100.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Number of Participants Who Experience Grades II-IV Acute GVHD	4 Participants

SECONDARY outcome

Timeframe: Day 100

Number of participants who experience grade III or IV acute GVHD by Day 100.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Number of Participants Who Experience Grades III-IV Acute GVHD	2 Participants

SECONDARY outcome

Timeframe: 2 years

Number of participants who experience chronic GVHD by two years after BMT.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Number of Participants Who Experience Chronic GVHD	1 Participants

SECONDARY outcome

Timeframe: Day 60

Number of participants with full donor chimerism at Day 60.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Number of Participants With Full Donor Chimerism	21 Participants

SECONDARY outcome

Timeframe: 1 year

Number of participants alive, without relapse, and without GVHD at 1 year.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
GVHD-free Relapse-free Survival (GRFS)	19 Participants

SECONDARY outcome

Timeframe: 1 year

Number of participants deceased for reasons related to BMT at 1 year.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplant n=21 Participants Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Transplant-related Mortality	2 Participants

Adverse Events

Bone Marrow Transplant

Serious events: 2 serious events

Other events: 0 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Bone Marrow Transplant n=21 participants at risk Non-myeloablative bone marrow transplant with a Thymoglobulin (ATG), fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Thymoglobulin: Day -9: 0.5 mg/kg Days -8 and -7: 2 mg/kg daily Fludarabine: Days -6 through -2: 30 mg/m\^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 365 Mycophenolate mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day)
Infections and infestations Gram negative rods Bacteremia	9.5% 2/21 • Adverse events were monitored and collected from time of consent up to one year.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Amy DeZern

Johns Hopkins University

Phone: 410-502-7208

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place