Trial Outcomes & Findings for Allo vs Hypomethylating/Best Supportive Care in MDS (BMTCTN1102) (NCT NCT02016781)
NCT ID: NCT02016781
Last Updated: 2023-03-03
Results Overview
The primary endpoint for this study is overall survival (OS) at three years post-consent. Death from any cause will be considered an event for this endpoint. Surviving participants are censored at the time of last follow-up. Three year OS estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy. The results posted are from the February 2020 interim analysis per protocol study design. Two interim analyses for efficacy were performed previously in January and November 2019 and presented to the Data and Safety Monitoring Board (DSMB). Results at the second analysis was crossing the efficacy boundary. Subsequently, the DSMB approved early release of study data as of February 2020.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
384 participants
Primary outcome timeframe
3 years
Results posted on
2023-03-03
Participant Flow
Participants were recruited from 34 centers between December 2013 and November 2018. The study opened to accrual on December 16, 2013 with 36 centers activated for enrollment. The study closed to accrual on November 9, 2018 and study completed on October 5, 2021.
Participants whose donors were found during the search were assigned to HCT arm. Participants whose donors were not found by the end of the search were assigned to Non-HCT arm.
Participant milestones
| Measure |
HCT Arm
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Interim Look for Primary Analysis
STARTED
|
260
|
124
|
|
Interim Look for Primary Analysis
COMPLETED
|
187
|
100
|
|
Interim Look for Primary Analysis
NOT COMPLETED
|
73
|
24
|
|
Final Database Lock
STARTED
|
261
|
123
|
|
Final Database Lock
COMPLETED
|
248
|
115
|
|
Final Database Lock
NOT COMPLETED
|
13
|
8
|
Reasons for withdrawal
| Measure |
HCT Arm
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Interim Look for Primary Analysis
Alive and on study
|
71
|
23
|
|
Interim Look for Primary Analysis
Withdrawal by Subject
|
2
|
1
|
|
Final Database Lock
Withdrawal by Subject
|
2
|
1
|
|
Final Database Lock
Lost to Follow-up
|
11
|
4
|
|
Final Database Lock
Missing data
|
0
|
3
|
Baseline Characteristics
Either KPS or ECOG were collected from each participant at enrollment, not both.
Baseline characteristics by cohort
| Measure |
HCT Arm
n=260 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
n=124 Participants
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
Total
n=384 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=260 Participants
|
0 Participants
n=124 Participants
|
0 Participants
n=384 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
105 Participants
n=260 Participants
|
44 Participants
n=124 Participants
|
149 Participants
n=384 Participants
|
|
Age, Categorical
>=65 years
|
155 Participants
n=260 Participants
|
80 Participants
n=124 Participants
|
235 Participants
n=384 Participants
|
|
Age, Continuous
|
65.6 year
STANDARD_DEVIATION 5.6 • n=260 Participants
|
66.0 year
STANDARD_DEVIATION 5.9 • n=124 Participants
|
65.7 year
STANDARD_DEVIATION 5.7 • n=384 Participants
|
|
Sex: Female, Male
Female
|
95 Participants
n=260 Participants
|
48 Participants
n=124 Participants
|
143 Participants
n=384 Participants
|
|
Sex: Female, Male
Male
|
165 Participants
n=260 Participants
|
76 Participants
n=124 Participants
|
241 Participants
n=384 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=260 Participants
|
9 Participants
n=124 Participants
|
20 Participants
n=384 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
233 Participants
n=260 Participants
|
108 Participants
n=124 Participants
|
341 Participants
n=384 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
16 Participants
n=260 Participants
|
7 Participants
n=124 Participants
|
23 Participants
n=384 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=260 Participants
|
1 Participants
n=124 Participants
|
2 Participants
n=384 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=260 Participants
|
2 Participants
n=124 Participants
|
10 Participants
n=384 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=260 Participants
|
0 Participants
n=124 Participants
|
0 Participants
n=384 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=260 Participants
|
9 Participants
n=124 Participants
|
15 Participants
n=384 Participants
|
|
Race (NIH/OMB)
White
|
234 Participants
n=260 Participants
|
105 Participants
n=124 Participants
|
339 Participants
n=384 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=260 Participants
|
0 Participants
n=124 Participants
|
0 Participants
n=384 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
11 Participants
n=260 Participants
|
7 Participants
n=124 Participants
|
18 Participants
n=384 Participants
|
|
Karnofsky Performance Score (KPS)
>=90
|
99 Participants
n=180 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
35 Participants
n=84 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
134 Participants
n=264 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
|
Karnofsky Performance Score (KPS)
<90
|
81 Participants
n=180 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
49 Participants
n=84 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
130 Participants
n=264 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
|
ECOG Performance Score
0
|
24 Participants
n=80 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
16 Participants
n=40 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
40 Participants
n=120 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
|
ECOG Performance Score
> 0
|
56 Participants
n=80 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
24 Participants
n=40 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
80 Participants
n=120 Participants • Either KPS or ECOG were collected from each participant at enrollment, not both.
|
|
MDS Subtype
Refractory cytopenia with unilineage dysplasia (RCUD)
|
5 Participants
n=260 Participants
|
1 Participants
n=124 Participants
|
6 Participants
n=384 Participants
|
|
MDS Subtype
Refractory anemia with ringed sideroblasts (RARS)
|
5 Participants
n=260 Participants
|
2 Participants
n=124 Participants
|
7 Participants
n=384 Participants
|
|
MDS Subtype
Refractory anemia with excess blasts (RAEB-1)
|
61 Participants
n=260 Participants
|
31 Participants
n=124 Participants
|
92 Participants
n=384 Participants
|
|
MDS Subtype
Refractory anemia with excess blasts (RAEB-2)
|
132 Participants
n=260 Participants
|
63 Participants
n=124 Participants
|
195 Participants
n=384 Participants
|
|
MDS Subtype
Refractory cytopenia with multilineage dysplasia (RCMD)
|
36 Participants
n=260 Participants
|
14 Participants
n=124 Participants
|
50 Participants
n=384 Participants
|
|
MDS Subtype
Myelodysplastic syndrome with isolated del(5q) (5q-syndrome)
|
6 Participants
n=260 Participants
|
7 Participants
n=124 Participants
|
13 Participants
n=384 Participants
|
|
MDS Subtype
Myelodysplastic syndrome (MDS), unclassifiable
|
15 Participants
n=260 Participants
|
6 Participants
n=124 Participants
|
21 Participants
n=384 Participants
|
|
MDS Duration from Diagnosis to Enrollment (months)
|
8.4 months
STANDARD_DEVIATION 21.6 • n=260 Participants
|
11.0 months
STANDARD_DEVIATION 27.1 • n=124 Participants
|
9.2 months
STANDARD_DEVIATION 23.5 • n=384 Participants
|
|
Identified Donor Type (HCT Arm only)
HLA Matched Related
|
80 Participants
n=260 Participants • Donor type is only available for HCT arm.
|
0 Participants
Donor type is only available for HCT arm.
|
80 Participants
n=260 Participants • Donor type is only available for HCT arm.
|
|
Identified Donor Type (HCT Arm only)
HLA Matched Unrelated
|
180 Participants
n=260 Participants • Donor type is only available for HCT arm.
|
0 Participants
Donor type is only available for HCT arm.
|
180 Participants
n=260 Participants • Donor type is only available for HCT arm.
|
|
Donor Gender (HCT Arm only)
Female
|
73 Participants
n=260 Participants • Donor gender is only available for HCT arm.
|
0 Participants
Donor gender is only available for HCT arm.
|
73 Participants
n=260 Participants • Donor gender is only available for HCT arm.
|
|
Donor Gender (HCT Arm only)
Male
|
130 Participants
n=260 Participants • Donor gender is only available for HCT arm.
|
0 Participants
Donor gender is only available for HCT arm.
|
130 Participants
n=260 Participants • Donor gender is only available for HCT arm.
|
|
Donor Gender (HCT Arm only)
Missing
|
57 Participants
n=260 Participants • Donor gender is only available for HCT arm.
|
0 Participants
Donor gender is only available for HCT arm.
|
57 Participants
n=260 Participants • Donor gender is only available for HCT arm.
|
|
HCT-CI (HCT Arm only)
0
|
41 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
0 Participants
HCT-CI is only available for HCT arm.
|
41 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
|
HCT-CI (HCT Arm only)
1
|
31 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
0 Participants
HCT-CI is only available for HCT arm.
|
31 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
|
HCT-CI (HCT Arm only)
2
|
35 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
0 Participants
HCT-CI is only available for HCT arm.
|
35 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
|
HCT-CI (HCT Arm only)
3
|
98 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
0 Participants
HCT-CI is only available for HCT arm.
|
98 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
|
HCT-CI (HCT Arm only)
Missing
|
55 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
0 Participants
HCT-CI is only available for HCT arm.
|
55 Participants
n=260 Participants • HCT-CI is only available for HCT arm.
|
|
Highest IPSS Score
Intermediate-2 (1.5-2.0)
|
173 Participants
n=260 Participants
|
81 Participants
n=124 Participants
|
254 Participants
n=384 Participants
|
|
Highest IPSS Score
High Risk (>=2.5)
|
87 Participants
n=260 Participants
|
43 Participants
n=124 Participants
|
130 Participants
n=384 Participants
|
|
Highest IPSS-R Score
Very Low
|
4 Participants
n=260 Participants
|
0 Participants
n=124 Participants
|
4 Participants
n=384 Participants
|
|
Highest IPSS-R Score
Low
|
2 Participants
n=260 Participants
|
0 Participants
n=124 Participants
|
2 Participants
n=384 Participants
|
|
Highest IPSS-R Score
Intermediate
|
79 Participants
n=260 Participants
|
34 Participants
n=124 Participants
|
113 Participants
n=384 Participants
|
|
Highest IPSS-R Score
High
|
82 Participants
n=260 Participants
|
51 Participants
n=124 Participants
|
133 Participants
n=384 Participants
|
|
Highest IPSS-R Score
Very High
|
93 Participants
n=260 Participants
|
39 Participants
n=124 Participants
|
132 Participants
n=384 Participants
|
|
Response to Hypomethylating Therapy
Complete Response
|
10 Participants
n=260 Participants
|
7 Participants
n=124 Participants
|
17 Participants
n=384 Participants
|
|
Response to Hypomethylating Therapy
Partial Response
|
46 Participants
n=260 Participants
|
23 Participants
n=124 Participants
|
69 Participants
n=384 Participants
|
|
Response to Hypomethylating Therapy
No Response
|
79 Participants
n=260 Participants
|
42 Participants
n=124 Participants
|
121 Participants
n=384 Participants
|
|
Response to Hypomethylating Therapy
Never had therapy
|
88 Participants
n=260 Participants
|
33 Participants
n=124 Participants
|
121 Participants
n=384 Participants
|
|
Response to Hypomethylating Therapy
Unknown
|
37 Participants
n=260 Participants
|
19 Participants
n=124 Participants
|
56 Participants
n=384 Participants
|
|
Cytogenetics Tested
Yes
|
241 Participants
n=260 Participants
|
112 Participants
n=124 Participants
|
353 Participants
n=384 Participants
|
|
Cytogenetics Tested
No
|
12 Participants
n=260 Participants
|
8 Participants
n=124 Participants
|
20 Participants
n=384 Participants
|
|
Cytogenetics Tested
Unknown or Missing
|
7 Participants
n=260 Participants
|
4 Participants
n=124 Participants
|
11 Participants
n=384 Participants
|
|
Results of Cytogenetics Test
Abnormalities Identified
|
151 Participants
n=241 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
81 Participants
n=112 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
232 Participants
n=353 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
|
Results of Cytogenetics Test
No Evaluable Metaphases
|
4 Participants
n=241 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
0 Participants
n=112 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
4 Participants
n=353 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
|
Results of Cytogenetics Test
No Abnormalities
|
84 Participants
n=241 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
31 Participants
n=112 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
115 Participants
n=353 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
|
Results of Cytogenetics Test
Missing
|
2 Participants
n=241 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
0 Participants
n=112 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
2 Participants
n=353 Participants • Results of cytogenetics test is only available for participants who had cytogenetics tested.
|
|
Number of Distinct Cytogenetic Abnormalities
1
|
43 Participants
n=151 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
28 Participants
n=81 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
71 Participants
n=232 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
|
Number of Distinct Cytogenetic Abnormalities
2
|
31 Participants
n=151 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
19 Participants
n=81 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
50 Participants
n=232 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
|
Number of Distinct Cytogenetic Abnormalities
3
|
20 Participants
n=151 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
14 Participants
n=81 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
34 Participants
n=232 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
|
Number of Distinct Cytogenetic Abnormalities
>=4
|
52 Participants
n=151 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
20 Participants
n=81 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
72 Participants
n=232 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
|
Number of Distinct Cytogenetic Abnormalities
Missing
|
5 Participants
n=151 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
0 Participants
n=81 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
5 Participants
n=232 Participants • Number of distinct cytogenetic abnormalities is only available for participants who had a abnormalities cytogenetics test result.
|
PRIMARY outcome
Timeframe: 3 yearsPopulation: The enrolled participants are included in the analyses.
The primary endpoint for this study is overall survival (OS) at three years post-consent. Death from any cause will be considered an event for this endpoint. Surviving participants are censored at the time of last follow-up. Three year OS estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy. The results posted are from the February 2020 interim analysis per protocol study design. Two interim analyses for efficacy were performed previously in January and November 2019 and presented to the Data and Safety Monitoring Board (DSMB). Results at the second analysis was crossing the efficacy boundary. Subsequently, the DSMB approved early release of study data as of February 2020.
Outcome measures
| Measure |
HCT Arm
n=260 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
n=124 Participants
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Overall Survival (OS)
|
47.9 percentage of participants
Interval 41.3 to 54.1
|
26.6 percentage of participants
Interval 18.4 to 35.6
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: The enrolled participants are included in the analyses.
LFS is defined as the time from the date of patient consent to the date of progression to AML or death from any cause, whichever comes first. Progression to AML is defined as \> 20% leukemic blasts in bone marrow or in the peripheral blood. Death from any cause or transformation of MDS to AML are considered events for this endpoint. Participants without either event are censored at the time of last follow-up. Three year leukemia-free survival probability estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy.
Outcome measures
| Measure |
HCT Arm
n=260 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
n=124 Participants
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Leukemia-free Survival (LFS)
|
35.8 percentage of participants
Interval 29.8 to 41.8
|
20.6 percentage of participants
Interval 13.3 to 29.1
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: The enrolled participants are included in the analyses. Only English and Spanish speaking patients were eligible to participate in the QOL component of this trial.
QOL will be compared between the 2 arms using the FACT-G instrument. FACT-G evaluates the health-related quality of life (HQL) of patients receiving treatment for cancer. FACT-G consists of four subscales developed and normed in cancer patients: Physical Well-being, Social/Family Well-being, Emotional Well-being, and Functional Well-being. The FACT-G score ranges 0-108. Each subscale is positively scored, with higher scores indicating better functioning. The self-reported questionnaire will be completed at enrollment and at 6, 12, 18, 24, and 36 months from consent. Results shown are FACT-G total scores.
Outcome measures
| Measure |
HCT Arm
n=260 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
n=124 Participants
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)
36 Months
|
90.3 score on a scale
Standard Error 2.0
|
79.7 score on a scale
Standard Error 5.9
|
|
Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)
Enrollment
|
81.5 score on a scale
Standard Error 1.1
|
79.3 score on a scale
Standard Error 1.9
|
|
Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)
6 Months
|
81.4 score on a scale
Standard Error 1.1
|
78.6 score on a scale
Standard Error 2.0
|
|
Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)
12 Months
|
84.0 score on a scale
Standard Error 1.2
|
80.8 score on a scale
Standard Error 2.2
|
|
Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)
18 Months
|
87.7 score on a scale
Standard Error 1.5
|
83.8 score on a scale
Standard Error 2.8
|
|
Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)
24 Months
|
89.0 score on a scale
Standard Error 1.6
|
87.0 score on a scale
Standard Error 3.4
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: The enrolled participants are included in the analyses. Only English and Spanish speaking patients were eligible to participate in the QOL component of this trial.
SF36 is being used in this protocol as a generic measure of quality of life (QOL). The self-reported questionnaires are completed at enrollment and at 6, 12, 18, 24, and 36 months from consent. The MOS SF-36 instrument is a general assessment of health QOL with eight components: Physical Functioning, Role Physical, Pain Index, General Health Perceptions, Vitality, Social Functioning, Role Emotional, and Mental Health Index. The sub scores for each of the eight components were computed based on the raw categorical values from the survey and range 0-100 with higher scores indicating better outcomes for each domain. Then overall Physical Component Summary (PCS) and Mental Component Summary (MCS) are computed using standardized algorithm for SF36. MCS and PCS scores range 0-100 with higher score indicating positive outcome. To facilitate comparison of the results with published norms, PCS and MCS are used as the outcome measures in summarizing the SF-36 data.
Outcome measures
| Measure |
HCT Arm
n=260 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
n=124 Participants
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
PCS at 6 Months
|
38.1 score on a scale
Standard Error 0.7
|
37.8 score on a scale
Standard Error 1.2
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
MCS at 6 Months
|
50.1 score on a scale
Standard Error 0.8
|
50.7 score on a scale
Standard Error 1.4
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
MCS at 12 Months
|
52.6 score on a scale
Standard Error 0.8
|
53.4 score on a scale
Standard Error 1.2
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
PCS at Enrollment
|
38.8 score on a scale
Standard Error 0.8
|
37.9 score on a scale
Standard Error 1.2
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
PCS at 12 Months
|
39.9 score on a scale
Standard Error 0.8
|
37.7 score on a scale
Standard Error 1.8
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
PCS at 18 Months
|
42.1 score on a scale
Standard Error 0.9
|
40.5 score on a scale
Standard Error 1.6
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
PCS at 24 Months
|
43.2 score on a scale
Standard Error 1.1
|
41.2 score on a scale
Standard Error 2.3
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
PCS at 36 Months
|
44.0 score on a scale
Standard Error 1.3
|
39.3 score on a scale
Standard Error 3.9
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
MCS at Enrollment
|
49.9 score on a scale
Standard Error 0.8
|
50.7 score on a scale
Standard Error 1.0
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
MCS at 18 Months
|
54.4 score on a scale
Standard Error 0.9
|
52.0 score on a scale
Standard Error 1.7
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
MCS at 24 Months
|
54.4 score on a scale
Standard Error 0.9
|
53.2 score on a scale
Standard Error 1.4
|
|
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
MCS at 36 Months
|
54.0 score on a scale
Standard Error 1.1
|
53.6 score on a scale
Standard Error 4.4
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: The enrolled participants are included in the analyses. Only English and Spanish speaking patients were eligible to participate in the QOL component of this trial.
QOL will be compared between the 2 arms using the EQ-5D survey. The EQ-5D contains a five-item survey with three response levels per item measuring mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D takes approximately 1 minute to complete (Agency for Healthcare Research and Quality, 2005). The EQ-5D score ranges -0.224 to 1. The maximum score of 1 indicates the best health state, by contrast with the scores of individual questions, where higher scores indicate more severe or frequent problems. The self-reported questionnaire will be completed at enrollment and at 6, 12, 18, 24, and 36 months from consent.
Outcome measures
| Measure |
HCT Arm
n=260 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
n=124 Participants
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Quality of Life (QOL) - EQ-5D
Enrollment
|
0.800 score on a scale
Standard Error 0.010
|
0.823 score on a scale
Standard Error 0.015
|
|
Quality of Life (QOL) - EQ-5D
6 Months
|
0.779 score on a scale
Standard Error 0.013
|
0.792 score on a scale
Standard Error 0.020
|
|
Quality of Life (QOL) - EQ-5D
12 Months
|
0.792 score on a scale
Standard Error 0.014
|
0.772 score on a scale
Standard Error 0.028
|
|
Quality of Life (QOL) - EQ-5D
18 Months
|
0.826 score on a scale
Standard Error 0.016
|
0.812 score on a scale
Standard Error 0.025
|
|
Quality of Life (QOL) - EQ-5D
24 Months
|
0.845 score on a scale
Standard Error 0.016
|
0.858 score on a scale
Standard Error 0.034
|
|
Quality of Life (QOL) - EQ-5D
36 Months
|
0.835 score on a scale
Standard Error 0.024
|
0.789 score on a scale
Standard Error 0.061
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: The treated participants are included in the analyses. This secondary analysis includes only treated participants who were compliant with their biologic assignment during the first six months following final assignment and excludes participants from the analysis if they died or dropped out before 90 days without a donor identified.
Time to event outcomes will be analyzed from the time of consent. Death from any cause will be considered an event for this endpoint. Surviving participants are censored at the time of last follow-up. Three-year OS estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy.
Outcome measures
| Measure |
HCT Arm
n=216 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
n=85 Participants
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Overall Survival (OS) in As-treated Population
|
49.4 percentage of participants
Interval 42.6 to 55.9
|
17.4 percentage of participants
Interval 9.4 to 27.5
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: The treated participants are included in the analyses. This secondary analysis includes only treated participants who were compliant with their biologic assignment during the first six months following final assignment and excludes participants from the analysis if they died or dropped out before 90 days without a donor identified.
LFS is defined as the time from the date of patient consent to the date of progression to AML or death from any cause, whichever comes first. Progression to AML is defined as \> 20% leukemic blasts in bone marrow or in the peripheral blood. Death from any cause or transformation of MDS to AML are considered events for this endpoint. Participants without either event are censored at the time of last follow-up. Three year leukemia-free survival probability estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy.
Outcome measures
| Measure |
HCT Arm
n=216 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
n=85 Participants
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Leukemia-free Survival (LFS) in As-treated Population
|
39.5 percentage of participants
Interval 32.9 to 46.1
|
11.2 percentage of participants
Interval 4.6 to 21.3
|
SECONDARY outcome
Timeframe: 27 months post-transplantPopulation: The enrolled participants in the HCT arm who received HCT from their assigned donor.
The time to event outcomes is evaluated from the time of transplant. Death from any cause will be considered an event for this endpoint. Surviving participants are censored at the time of last follow-up. OS estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy.
Outcome measures
| Measure |
HCT Arm
n=216 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants on HCT Arm With Overall Survival (OS)
|
55.7 percentage of participants
Interval 48.4 to 62.4
|
—
|
SECONDARY outcome
Timeframe: 27 months post-transplantPopulation: The enrolled participants in the HCT arm who received HCT from their assigned donor.
Outcome Measure Description: The time to event outcomes is evaluated from the time of transplant. Disease relapse is defined as: Satisfying criteria for evolution into acute leukemia; or reappearance of pre-transplant morphologic abnormalities, detected in bone marrow specimens; or reappearance of pre-transplant cytogenetic abnormality in at least one metaphase on each of two separate consecutive examinations at least one month apart, regardless of the number of metaphases analyzed; or institution of any therapy to treat relapsed disease (institution of any therapy not meant for maintenance or prevention), including withdrawal of immunosuppressive therapy or DLI. Relapse estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy.
Outcome measures
| Measure |
HCT Arm
n=216 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants on HCT Arm With Disease Relapse
|
29.6 percentage of participants
Interval 23.5 to 35.9
|
—
|
SECONDARY outcome
Timeframe: 27 months post-transplantPopulation: The enrolled participants in the HCT arm who received HCT from their assigned donor.
The time to event outcomes is evaluated from the time of transplant. Death or disease relapse/progression will be considered as events for this endpoint. Surviving participants are censored at the time of last follow-up. DFS estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy.
Outcome measures
| Measure |
HCT Arm
n=216 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants on HCT Arm With Disease-free Survival (DFS)
|
49.7 percentage of participants
Interval 42.6 to 56.5
|
—
|
SECONDARY outcome
Timeframe: 27 months post-transplantPopulation: The enrolled participants in the HCT arm who received HCT from their assigned donor.
The time to event outcomes is evaluated from the time of transplant. The events are deaths prior to disease relapse. TRM estimates are adjusted for age, race/ethnicity, performance status, IPSS score, duration of disease, and response to prior hypomethylating therapy.
Outcome measures
| Measure |
HCT Arm
n=216 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants on HCT Arm With Treatment-related Mortality
|
20.6 percentage of participants
Interval 15.3 to 26.5
|
—
|
SECONDARY outcome
Timeframe: 27 months post-transplantPopulation: Enrolled participants in the HCT arm who received HCT from their assigned donor and who had Grade II-IV Acute GVHD data from CIBMTR are included.
Grade II-IV aGVHD is the event. aGVHD will be graded according to the BMT CTN Manual of Procedures (MOP). Staging for skin: Stage 1. \<25% rash; 2. 25-50%; 3. \>50%; 4. generalized erythroderma with bullae. Staging for GI: Stage 1. Diarrhea\>500ml/d or persistent nausea; 2. \>1000ml/d; 3. \>1500ml/d; 4. Large volume diarrhea and severe abdominal pain +- ileus. Staging for Liver: Stage 1. bilirubin 2-3mg/dl; 2. bilirubin 3-6 mg/dl; 3. bilirubin 6-15 mg/dl; 4. bilirubin\>15mg/dl. aGVHD grading is performed by the consensus conference criteria (Przepiorka et al. 1995). Grade I aGVHD is defined as Skin stage of 1-2 and stage 0 for both GI and liver organs. Grade II is stage 3 of skin, or stage 1 of GI, or stage 1 of liver. Grade III is stage 2-4 for GI, or stage 2-3 of liver. Grade IV is stage 4 of skin, or stage 4 of liver.
Outcome measures
| Measure |
HCT Arm
n=201 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants on HCT Arm With Grade II-IV Acute GVHD (aGVHD)
|
43.1 percentage of participants
Interval 36.1 to 49.9
|
—
|
SECONDARY outcome
Timeframe: 27 months post-transplantPopulation: Enrolled participants in the HCT arm who received HCT from their assigned donor and who had Grade III-IV Acute GVHD data from CIBMTR are included.
The time to event outcomes is evaluated from the time of transplant. Grade III-IV Acute GVHD will be considered as events for this endpoint.
Outcome measures
| Measure |
HCT Arm
n=201 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
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Non-HCT Arm
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
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|---|---|---|
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Percentage of Participants on HCT Arm With Grade III-IV Acute GVHD
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17.1 percentage of participants
Interval 12.2 to 22.7
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—
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SECONDARY outcome
Timeframe: 27 months post-transplantPopulation: Enrolled participants in the HCT arm who received HCT from their assigned donor and who had Chronic GVHD data from CIBMTR are included.
The time to event outcomes is evaluated from the time of transplant. Chronic GVHD will be considered as events for this endpoint. Data will be collected and reviewed according to the recommendations of the NIH Consensus Criteria. Eight organs will be scored on a 0-3 scale to reflect degree of chronic GVHD involvement. Liver and pulmonary function test results and use of systemic therapy for treatment of chronic GVHD will also be recorded. This secondary endpoint of chronic GVHD will include mild, moderate and severe chronic GVHD based on NIH Consensus Criteria.
Outcome measures
| Measure |
HCT Arm
n=202 Participants
Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
All subjects are initially assigned to the non-transplant arm. Subjects are re-assigned to the transplant arm should a suitable donor be identified within 90 days of informed consent.
Bone marrow or peripheral blood stem cell transplant from a fully matched related (6/6) or unrelated (8/8) donor. Donors must meet institutional selection criteria, and there is no age restriction for sibling donors. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.
The following limits on conditioning dose intensity delineate myeloablative regimens:
1. TBI doses of ≥ 500 (unfractionated) cGy and ≥ 800 cGy (fractionated)
All supportive care will be given in keeping with the BMT CTN Manual of Procedures (MOP) and local institutional guidelines. All patients will receive prophylaxis against bacterial, fungal, and viral infections during the post-HCT period according to institutional standards.
2. Busulfan dose ≥ 9.5 mg/kg
3. Melphalan ≥ 150 mg/m2
|
Non-HCT Arm
Non-Transplant Therapy/Best Supportive Care The specific non-transplant treatment regimen will be at the discretion of the treating physician.
Hypomethylating therapy is the accepted standard therapy of treatment naïve patients with Int-2/High Risk MDS not undergoing transplantation. Azacytidine: 75 mg/m2 by subcutaneous injection or IV for 7 days; 28 day cycles. Or Decitabine: 20 mg/m2 IV daily for 5 days; 28 day cycles.
All supportive care will be given in keeping with local institutional guidelines.
|
|---|---|---|
|
Percentage of Participants on HCT Arm With Chronic GVHD
|
55.5 percentage of participants
Interval 47.8 to 62.5
|
—
|
Adverse Events
HCT Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 125 deaths
Non-HCT Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 86 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place