Allo vs Hypomethylating/Best Supportive Care in MDS (BMTCTN1102)

A Multi-Center Biologic Assignment Trial Comparing Allogeneic Hematopoietic Cell Transplant to Hypomethylating Therapy or Best Supportive Care in Patients w/Intermediate-2 & High Risk Myelodysplastic Syndrome (BMTCTN1102)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02016781

Enrollment

384

Registered

2013-12-20

Start date

2013-12-16

Completion date

2021-10-05

Last updated

2023-03-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

MDS

Keywords

Myelodysplastic Syndrome

Brief summary

This study is designed as a multicenter trial, with biological assignment to one of two study arms; Arm 1: Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT), Arm 2: Non-Transplant Therapy/Best Supportive Care.

Detailed description

Background: MDS is a clonal disorder of hematopoietic precursors and stem cells, which may evolve to a terminal phase resembling acute leukemia. A subject of clinical urgency for researchers, clinicians, patients, and health care underwriters such as Medicare, is the role of allogeneic hematopoietic cell transplantation (alloHCT) in the treatment of older patients with higher risk myelodysplastic syndromes (MDS). The use of reduced intensity conditioning (RIC) regimens has extended HCT to the care of older patients with acute myelogenous leukemia (AML) and lymphoma and a number of retrospective and phase II trials for patients with MDS now show the curative potential of RIC alloHCT in selected patients. This protocol is designed to evaluate the relative benefits of RIC alloHCT compared to non-transplant therapies focusing on overall survival. This will be done by having patients biologically assigned to the alloHCT arm or the hypomethylating therapy/best supportive care arm and following them for survival at 3 years.

Interventions

PROCEDUREAllogeneic Hematopoietic Cell Transplant

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.

PROCEDUREHypomethylating Therapy / Best Supportive Care

The specific non-transplant treatment regimen will be at the discretion of the treating physician.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Masking description

No parties are masked in this trial.

Intervention model description

Two arms will enroll and have data collected on them simultaneously.

Eligibility

Sex/Gender

ALL

Age

50 Years to 75 Years

Healthy volunteers

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)	3 years	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.
Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)	3 years	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.
Quality of Life (QOL) - EQ-5D	3 years	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.
Percentage of Participants With Overall Survival (OS) in As-treated Population	3 years	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.
Percentage of Participants With Leukemia-free Survival (LFS) in As-treated Population	3 years	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.
Percentage of Participants on HCT Arm With Overall Survival (OS)	27 months post-transplant	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.
Percentage of Participants With Leukemia-free Survival (LFS)	3 years	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.
Percentage of Participants on HCT Arm With Disease-free Survival (DFS)	27 months post-transplant	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.
Percentage of Participants on HCT Arm With Treatment-related Mortality	27 months post-transplant	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.
Percentage of Participants on HCT Arm With Grade II-IV Acute GVHD (aGVHD)	27 months post-transplant	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.
Percentage of Participants on HCT Arm With Grade III-IV Acute GVHD	27 months post-transplant	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.
Percentage of Participants on HCT Arm With Chronic GVHD	27 months post-transplant	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.
Percentage of Participants on HCT Arm With Disease Relapse	27 months post-transplant	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.

Countries

United States

Participant flow

Recruitment details

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.

Pre-assignment details

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.

Participants by arm

Arm	Count
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	260
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.	124
Total	384

Withdrawals & dropouts

Period	Reason	FG000	FG001
Final Database Lock	Lost to Follow-up	11	4
Final Database Lock	Missing data	0	3
Final Database Lock	Withdrawal by Subject	2	1
Interim Look for Primary Analysis	Alive and on study	71	23
Interim Look for Primary Analysis	Withdrawal by Subject	2	1

Baseline characteristics

Characteristic	HCT Arm	Non-HCT Arm	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	155 Participants	80 Participants	235 Participants
Age, Categorical Between 18 and 65 years	105 Participants	44 Participants	149 Participants
Age, Continuous	65.6 year STANDARD_DEVIATION 5.6	66.0 year STANDARD_DEVIATION 5.9	65.7 year STANDARD_DEVIATION 5.7
Cytogenetics Tested No	12 Participants	8 Participants	20 Participants
Cytogenetics Tested Unknown or Missing	7 Participants	4 Participants	11 Participants
Cytogenetics Tested Yes	241 Participants	112 Participants	353 Participants
Donor Gender (HCT Arm only) Female	73 Participants	0 Participants	73 Participants
Donor Gender (HCT Arm only) Male	130 Participants	0 Participants	130 Participants
Donor Gender (HCT Arm only) Missing	57 Participants	0 Participants	57 Participants
ECOG Performance Score 0	24 Participants	16 Participants	40 Participants
ECOG Performance Score > 0	56 Participants	24 Participants	80 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants	9 Participants	20 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	233 Participants	108 Participants	341 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	16 Participants	7 Participants	23 Participants
HCT-CI (HCT Arm only) 0	41 Participants	0 Participants	41 Participants
HCT-CI (HCT Arm only) 1	31 Participants	0 Participants	31 Participants
HCT-CI (HCT Arm only) 2	35 Participants	0 Participants	35 Participants
HCT-CI (HCT Arm only) 3	98 Participants	0 Participants	98 Participants
HCT-CI (HCT Arm only) Missing	55 Participants	0 Participants	55 Participants
Highest IPSS-R Score High	82 Participants	51 Participants	133 Participants
Highest IPSS-R Score Intermediate	79 Participants	34 Participants	113 Participants
Highest IPSS-R Score Low	2 Participants	0 Participants	2 Participants
Highest IPSS-R Score Very High	93 Participants	39 Participants	132 Participants
Highest IPSS-R Score Very Low	4 Participants	0 Participants	4 Participants
Highest IPSS Score High Risk (>=2.5)	87 Participants	43 Participants	130 Participants
Highest IPSS Score Intermediate-2 (1.5-2.0)	173 Participants	81 Participants	254 Participants
Identified Donor Type (HCT Arm only) HLA Matched Related	80 Participants	0 Participants	80 Participants
Identified Donor Type (HCT Arm only) HLA Matched Unrelated	180 Participants	0 Participants	180 Participants
Karnofsky Performance Score (KPS) <90	81 Participants	49 Participants	130 Participants
Karnofsky Performance Score (KPS) >=90	99 Participants	35 Participants	134 Participants
MDS Duration from Diagnosis to Enrollment (months)	8.4 months STANDARD_DEVIATION 21.6	11.0 months STANDARD_DEVIATION 27.1	9.2 months STANDARD_DEVIATION 23.5
MDS Subtype Myelodysplastic syndrome (MDS), unclassifiable	15 Participants	6 Participants	21 Participants
MDS Subtype Myelodysplastic syndrome with isolated del(5q) (5q-syndrome)	6 Participants	7 Participants	13 Participants
MDS Subtype Refractory anemia with excess blasts (RAEB-1)	61 Participants	31 Participants	92 Participants
MDS Subtype Refractory anemia with excess blasts (RAEB-2)	132 Participants	63 Participants	195 Participants
MDS Subtype Refractory anemia with ringed sideroblasts (RARS)	5 Participants	2 Participants	7 Participants
MDS Subtype Refractory cytopenia with multilineage dysplasia (RCMD)	36 Participants	14 Participants	50 Participants
MDS Subtype Refractory cytopenia with unilineage dysplasia (RCUD)	5 Participants	1 Participants	6 Participants
Number of Distinct Cytogenetic Abnormalities 1	43 Participants	28 Participants	71 Participants
Number of Distinct Cytogenetic Abnormalities 2	31 Participants	19 Participants	50 Participants
Number of Distinct Cytogenetic Abnormalities 3	20 Participants	14 Participants	34 Participants
Number of Distinct Cytogenetic Abnormalities >=4	52 Participants	20 Participants	72 Participants
Number of Distinct Cytogenetic Abnormalities Missing	5 Participants	0 Participants	5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	2 Participants
Race (NIH/OMB) Asian	8 Participants	2 Participants	10 Participants
Race (NIH/OMB) Black or African American	6 Participants	9 Participants	15 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants	7 Participants	18 Participants
Race (NIH/OMB) White	234 Participants	105 Participants	339 Participants
Response to Hypomethylating Therapy Complete Response	10 Participants	7 Participants	17 Participants
Response to Hypomethylating Therapy Never had therapy	88 Participants	33 Participants	121 Participants
Response to Hypomethylating Therapy No Response	79 Participants	42 Participants	121 Participants
Response to Hypomethylating Therapy Partial Response	46 Participants	23 Participants	69 Participants
Response to Hypomethylating Therapy Unknown	37 Participants	19 Participants	56 Participants
Results of Cytogenetics Test Abnormalities Identified	151 Participants	81 Participants	232 Participants
Results of Cytogenetics Test Missing	2 Participants	0 Participants	2 Participants
Results of Cytogenetics Test No Abnormalities	84 Participants	31 Participants	115 Participants
Results of Cytogenetics Test No Evaluable Metaphases	4 Participants	0 Participants	4 Participants
Sex: Female, Male Female	95 Participants	48 Participants	143 Participants
Sex: Female, Male Male	165 Participants	76 Participants	241 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	125 / 260	86 / 124
other Total, other adverse events	0 / 260	0 / 124
serious Total, serious adverse events	0 / 260	0 / 124

Outcome results

Primary

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.

Time frame: 3 years

Population: The enrolled participants are included in the analyses.

Arm	Measure	Value (NUMBER)
HCT Arm	Percentage of Participants With Overall Survival (OS)	47.9 percentage of participants
Non-HCT Arm	Percentage of Participants With Overall Survival (OS)	26.6 percentage of participants

Comparison: 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.p-value: 0.0001Wald test

Comparison: This subgroup analysis investigated the differential impact of response to hypomethylating therapy (No Response to Hypomethylation vs. Any Response or Hematologic Improvement to Hypomethylation vs. No Prior Hypomethylation) on the treatment effect for OS at three years post-consent for the HCT arm vs. the non-HCT arm. The analysis was conducted using pseudo-value regression models via an interaction term between the factor and the treatment group with a logit link function.p-value: 0.3345pseudo-value regression models

Comparison: This subgroup analysis investigated the differential impact of patient age (\< vs. \>= 65) on the treatment effect for OS at three years post-consent for the HCT arm vs. the non-HCT arm. The analysis was conducted using pseudo-value regression models via an interaction term between the factor and the treatment group with a logit link function.p-value: 0.7328pseudo-value regression models

Comparison: This subgroup analysis investigated the differential impact of disease duration (less than vs. 3 months or more) on the treatment effect for OS at three years post-consent for the HCT arm vs. the non-HCT arm. The analysis was conducted using pseudo-value regression models via an interaction term between the factor and the treatment group with a logit link function.p-value: 0.6261pseudo-value regression models

Comparison: This subgroup analysis investigated the differential impact of IPSS score (Intermediate-2 vs. High) on the treatment effect for OS at three years post-consent for the HCT arm vs. the non-HCT arm. The analysis was conducted using pseudo-value regression models via an interaction term between the factor and the treatment group with a logit link function.p-value: 0.4134pseudo-value regression models

Comparison: Statistical Analysis 6: This subgroup analysis investigated the differential impact of IPSS-R score (Very Low, Low, or Intermediate vs. High vs. Very High) on the treatment effect for OS at three years post-consent for the HCT arm vs. the non-HCT arm. The analysis was conducted using pseudo-value regression models via an interaction term between the factor and the treatment group with a logit link function.p-value: 0.3147pseudo-value regression models

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.