Allo vs Hypomethylating/Best Supportive Care in MDS (BMTC... | NCT02016781

ID	Type	Description	Link
2U10HL069294-11	U.S. NIH Grant/Contract		View source
5U24CA076518	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH
National Cancer Institute (NCI)	NIH
Blood and Marrow Transplant Clinical Trials Network	NETWORK

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Transplant	Active Comparator	Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)	Procedure: Allogeneic Hematopoietic Cell Transplant
Hypomethylating Therapy / Best Supportive Care	Active Comparator	The specific non-transplant treatment regimen will be at the discretion of the treating physician.	Procedure: Hypomethylating Therapy / Best Supportive Care

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Allogeneic Hematopoietic Cell Transplant	Procedure	Bone marrow or peripheral blood stem cell transplant.from a fully matched related (6/6) or unrelated (8/8) donor. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Overall Survival (OS)	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.	3 years

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Leukemia-free Survival (LFS)	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients fulfilling the following criteria will be eligible for entry into this study:
1. Patients with de novo MDS who have, or have previously had, Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is NOT a requirement.
2. Patients must have an acceptable MDS subtype:
  - Refractory cytopenia with unilineage dysplasia (RCUD) (includes refractory anemia (RA))
  - Refractory anemia with ringed sideroblasts (RARS)
  - Refractory anemia with excess blasts (RAEB-1)
  - Refractory anemia with excess blasts (RAEB-2)
  - Refractory cytopenia with multilineage dysplasia (RCMD)
  - Myelodysplastic syndrome with isolated del(5q) (5q-syndrome)
  - Myelodysplastic syndrome (MDS), unclassifiable
3. Patients must have fewer than 20% marrow blasts within 60 days of consent.
4. Patients may have received prior therapy for the treatment of MDS, including but not limited to: growth factor, transfusion support, immunomodulatory (IMID) therapy, DNA hypomethylating therapy, or cytotoxic chemotherapy prior to enrollment.
5. Age 50.0-75.0 years.
6. Karnofsky performance status > 70 or Eastern Cooperative Oncology Group (ECOG) ≤ 1.
7. Patients are eligible if no formal unrelated donor search has been activated prior to date of consent. A formal unrelated donor search begins at the time at which samples are requested from potential National Marrow Donor Program (NMDP) donors. Patients who have started a sibling donor search or who have found a matched sibling donor are eligible.
8. Patients and physicians must be willing to comply with treatment assignment:
  1. No intent to proceed with alloHCT using donor sources not specified in this protocol, including human leukocyte antigen (HLA)-mismatched related or unrelated donors (< 6/6 HLA related matched or < 8/8 HLA unrelated matched) or umbilical cord blood unit(s).
  2. No intent to use myeloablative conditioning regimens.
  3. Intent to proceed with RIC alloHCT if a matched sibling or matched unrelated donor is identified. There is no requirement as to the timing of the transplantation.
9. Patients must be considered to be suitable RIC alloHCT candidates at the time of enrollment based on medical history, physical examination, and available laboratory tests. Specific testing for organ function is not required for eligibility but, if available, these tests should be used to judge eligibility.
10. Signed informed consent

Exclusion Criteria:

Patients with the following will be ineligible for registration onto this study:
1. Therapy-related MDS (defined as the occurrence of MDS due to prior exposure to systemic chemotherapy and/or radiation for malignancy)
2. Current or prior diagnosis of AML
3. Chronic myelomonocytic leukemia or myelodysplastic/myeloproliferative neoplasm (unacceptable MDS subtypes); uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement) at time of enrollment.
4. Patients with prior malignancies, except treated non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative surgery without chemotherapy/radiation therapy > 5 years previously will be allowed. Cancer treated with curative surgery < 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
5. Prior autologous or allogeneic HCT
6. Human Immunodeficiency Virus (HIV) infection
7. Patients of childbearing potential unwilling to use contraceptive techniques
8. Patients with psychosocial conditions that would prevent study compliance

Name	Affiliation	Role
Mary Horowitz, MD, MS	Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope National Medical Center		Duarte	California	91010	United States
Stanford Hospital and Clinics

PubMed Identifier	Type	Citation	Retractions
24972249	Background	Saber W, Le Rademacher J, Sekeres M, Logan B, Lewis M, Mendizabal A, Leifer E, Appelbaum FR, Horowitz MM, Nakamura R, Cutler CS. Multicenter biologic assignment trial comparing reduced-intensity allogeneic hematopoietic cell transplant to hypomethylating therapy or best supportive care in patients aged 50 to 75 with intermediate-2 and high-risk myelodysplastic syndrome: Blood and Marrow Transplant Clinical Trials Network #1102 study rationale, design, and methods. Biol Blood Marrow Transplant. 2014 Oct;20(10):1566-72. doi: 10.1016/j.bbmt.2014.06.010. Epub 2014 Jun 24.
38261970

Label	URL
National Marrow Donor Program	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP_ICF	Yes	Yes	Yes	Study Protocol, Statistical Analysis Plan, and Informed Consent Form	Nov 28, 2018

Arm/Group Information

ID	Title	Description
BG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2
BG001	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	OG00047.9(41.3 to 54.1) OG00126.6(18.4 to 35.6)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that the rates of three-year OS are the same for both treatments. The results posted are from the interim analysis per protocol study design.	Wald test	Wald test of difference in adjusted OS estimates.	0.0001	Statistical significance was determined using a pre-specified threshold of 0.05.													Superiority

Secondary

Percentage of Participants With Leukemia-free Survival (LFS)

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.

The enrolled participants are included in the analyses.

Posted

Number

95% Confidence Interval

percentage of participants

3 years

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)

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.

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.

Posted

Mean

Standard Error

score on a scale

3 years

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)

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.

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.

Posted

Mean

Standard Error

score on a scale

3 years

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Quality of Life (QOL) - EQ-5D

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.

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.

Posted

Mean

Standard Error

score on a scale

3 years

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Percentage of Participants With Overall Survival (OS) in As-treated Population

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

3 years

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Percentage of Participants With Leukemia-free Survival (LFS) in As-treated Population

Posted

Number

95% Confidence Interval

percentage of participants

3 years

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Percentage of Participants on HCT Arm With Overall Survival (OS)

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.

The enrolled participants in the HCT arm who received HCT from their assigned donor.

Posted

Number

95% Confidence Interval

percentage of participants

27 months post-transplant

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Percentage of Participants on HCT Arm With Disease Relapse

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.

The enrolled participants in the HCT arm who received HCT from their assigned donor.

Posted

Number

95% Confidence Interval

percentage of participants

27 months post-transplant

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Percentage of Participants on HCT Arm With Disease-free Survival (DFS)

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.

The enrolled participants in the HCT arm who received HCT from their assigned donor.

Posted

Number

95% Confidence Interval

percentage of participants

27 months post-transplant

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Percentage of Participants on HCT Arm With Treatment-related Mortality

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.

The enrolled participants in the HCT arm who received HCT from their assigned donor.

Posted

Number

95% Confidence Interval

percentage of participants

27 months post-transplant

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Percentage of Participants on HCT Arm With Grade II-IV Acute GVHD (aGVHD)

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

27 months post-transplant

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Secondary

Percentage of Participants on HCT Arm With Grade III-IV Acute GVHD

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

27 months post-transplant

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2
OG001

Secondary

Percentage of Participants on HCT Arm With Chronic GVHD

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.

Enrolled participants in the HCT arm who received HCT from their assigned donor and who had Chronic GVHD data from CIBMTR are included.

Posted

Number

95% Confidence Interval

percentage of participants

27 months post-transplant

ID	Title	Description
OG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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: 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. Busulfan dose ≥ 9.5 mg/kg Melphalan ≥ 150 mg/m2	125	260	0	260	0	260
EG001	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.	86	124	0	124	0	124

ID	Term
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases