Acute Leukemia, Myelodysplasia
Conditions
Keywords
Acute Leukemia, Myelodysplasia, GVHD Prophylaxis, Chronic GVHD
Brief summary
The study is designed as a three arm randomized Phase III, multicenter trial comparing two calcineurin inhibitor (CNI)-free strategies for Graft-versus-Host Disease (GVHD) prophylaxis to standard tacrolimus and methotrexate (Tac/Mtx) in patients with hematologic malignancies undergoing myeloablative conditioning hematopoietic stem cell transplantation.
Detailed description
Chronic Graft-versus-Host Disease (GVHD) is a complication that affects many hematopoietic stem cell transplant (HSCT) survivors; it occurs when the new cells from a transplant attack the recipient's body. The current standard GVHD prophylaxis regimen for patients with hematologic malignancies undergoing HSCT involves a combination of immunosuppressive agents given for the first 6 months after transplant. Often, patients develop GVHD and continue on these agents for much longer periods. The combination of calcineurin inhibitors (tacrolimus and cyclosporine A) with methotrexate (MTX) is the most common GVHD prophylaxis used worldwide in the context of myeloablative conditioning transplants. This regimen demonstrates better control of acute GVHD, but is less effective against chronic GVHD. Management of chronic GVHD remains a challenge and it has become a significant health problem in transplant survivors with more frequent use of mobilized peripheral blood stem cells. Additionally, several issues arise with the standard approach including various toxicity symptoms and side effects, increased risk of thrombotic microangiopathy due to CNI, no prevention of other infectious diseases, and no prevention for disease relapse. This standard strategy of Tac/MTX will be used as a control in comparison to two other treatment plans both utilizing CNI-free methods: CD34 selected T-cell depletion in peripheral blood stem cell (PBSC) grafts, and infusion of bone marrow (BM) grafts followed by post-transplant Cyclophosphamide (PTCy). Study participants will be randomized to one of these three treatment arms.
Interventions
PROCEDUREUnmanipulated Bone Marrow Graft with Tacrolimus/Methotrexate
Unmanipulated BM grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
PROCEDUREMobilized CD34-selected Peripheral Blood Stem Cell graft
Mobilized CD34-selected PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
PROCEDUREUnmanipulated Bone Marrow Graft with Cyclophosphamide
Unmanipulated BM grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
DRUGCyclophosphamide
Mesna will be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide or administered per institutional standards. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of Mesna is equal to 80% of the total daily dose of cyclophosphamide. Cyclophosphamide 50 mg/kg will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume).
DRUGTacrolimus
Tacrolimus will be given orally or intravenously per institutional standards starting Day -3. The dose of tacrolimus may be rounded to the nearest 0.5 mg for oral formulations. Subsequent dosing will be based on blood levels, with a target of 5-15 ng/ml. If patients are on medications which alter the metabolism of tacrolimus (e.g. azoles), the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.
DRUGMethotrexate
Methotrexate will be administered at the doses of 15 mg/m\^2 IV bolus on Day +1, and 10 mg/m\^2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +1 dose of methotrexate should be given at least 24 hours after the hematopoietic stem cell infusion. Dose reduction of MTX due to worsening creatinine clearance after initiation of conditioning regimen, high serum levels or development of oral mucositis is allowed according to institutional practices. Leucovorin rescue is allowed according to institutional practices.
Sponsors
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females aged ≥ 1.0 year and \< 66.0 years 2. Patients with acute leukemia in morphologic complete remission with or without hematologic recovery or with myelodysplasia (MDS) with no circulating blasts and with less than 5% blasts in the bone marrow. Patients with CMML must have a WBC count ≤ 10,000 cells/µL and \< 5% blasts in the marrow. Patients with ≥ 5% blasts due to a regenerating marrow must contact the protocol chairs for review. 3. Planned myeloablative conditioning regimen 4. Patients must have a related or unrelated donor as follows: 1. Related donor must be an 8/8 match for human leukocyte antigen (HLA)-A, -B, and -C at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing. Pediatric related donors must weigh ≥ 25.0 kg., must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter, must be willing to (1) donate bone marrow and (2) receive G-CSF followed by donation of peripheral blood stem cells (product to be determined by randomization post enrollment) and must meet institutional criteria for donation. 2. Unrelated donor must be an 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be medically eligible to donate according to National Marrow Donor Program (NMDP) (or equivalent donor search organization) criteria. At time of enrollment, the donor should not have any known preferences or contraindications to donate bone marrow or peripheral blood stem cells. (Selection of unrelated donors is to be performed according to institutional practice. It is recommended that the time from collection to initiation of the cell processing be considered when prioritizing donors, as data shows better results for CD34 selection when cell processing begins within 36 hours of the end of collection) 5. Cardiac function: Ejection fraction at rest ≥ 45.0% or shortening fraction of ≥ 27.0% by echocardiogram or radionuclide scan (MUGA). 6. Estimated creatinine clearance (for patients \> 12 years) greater than 50.0 mL/minute (using the Cockcroft-Gault formula and actual body weight); for pediatric patients (\> 1 year to 12 years), Glomerular Filtration Rate (GFR) estimated by the updated Schwartz formula ≥ 90.0 mL/min/1.73 m\^2. If the estimated creatinine clearance is \< 90 mL/min/1.73 m\^2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be \> 70.0 mL/min/1.73 m\^2. 7. Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 50% (adjusted for hemoglobin), and forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) ≥ 50%; for children who are unable to perform for Pulmonary Function Tests (PFTs) due to age or developmental ability, there must be no evidence of dyspnea and no need for supplemental oxygen, as evidenced by O2 saturation ≥ 92% on room air. 8. Liver function: total bilirubin \< 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \< 2.5x the upper limit of normal. 9. Signed informed consent.
Exclusion criteria
1. Prior autologous or allogeneic hematopoietic stem cell transplant 2. Karnofsky or Lansky Performance Score \< 70% 3. Active central nervous system (CNS) involvement by malignant cells 4. Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment 5. Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated 6. Patients seropositive for HIV-1 or -2 7. Patients seropositive for Human T-Lymphotrophic Virus (HTLV)-I or -II 8. Patients with active Hepatitis B or C viral replication by polymerase chain reaction (PCR) 9. Documented allergy to iron dextran or murine proteins 10. Women who are pregnant (positive serum or urine βHCG) or breastfeeding 11. Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use 2 effective forms of birth control or abstinence for one year after transplantation 12. History of uncontrolled autoimmune disease or on active treatment 13. Patients with prior malignancies, except resected non-melanoma or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent \< 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. 14. Patient unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests 15. Planned post-transplant maintenance therapy except for FLT3 inhibitors or TKIs must be declared prior to randomization. 16. If it is known prior to enrollment that the hematopoietic stem cell product will need to be cryopreserved, the patient should not be enrolled. 17. German centers only: Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or participation in any other interventional clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chronic GVHD-free, Relapse-free Survival (CRFS) Probability | 2 years | The primary endpoint of the trial is Chronic GVHD/Relapse-Free Survival (CRFS), treated as a time to event variable. An event for this time to event outcome is defined as moderate to severe chronic GVHD, disease relapse, or death by any cause. Participant will be censored if lost to follow up prior to 2 years. Time is from randomization to the event of moderate to severe chronic GVHD, disease relapse, death, last follow up, or 2 years, whichever comes first. The primary analysis is performed using the intent-to-treat principle (ITT) so that all randomized patients are included in the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Relapse-free Survival | 2 Years | The events for this endpoint RFS are death and relapse of the underlying malignancy. The analyses of this endpoint use the transplanted populations and time is from transplant to the event of disease relapse or death, or last follow up, whichever comes first. |
| Percentage of Participants With Treatment-related Mortality | 2 Years | The events for this endpoint TRM are deaths prior to relapse of the underlying malignancy. The analyses of this endpoint will use the transplanted populations, and time will be from transplant to the first of disease relapse, death, or last follow up. TRM are evaluated using the cumulative incidence function. Deaths without relapse are the events for this endpoint and relapse is a competing risk for this endpoint. |
| Participants With Immunosuppression-free Survival | 1 Year | Patients who are alive, relapse-free, and do not need ongoing immune suppression to control GVHD at one year post HSCT are considered successes for this endpoint. Immune suppression is defined as any systemic agents used to control or suppress GVHD. |
| Percentage of Participants With Disease Relapse | 2 Years | Relapse is defined by either morphological evidence of acute leukemia or MDS consistent with pre-transplant features, or radiologic evidence of lymphoma, documented or not by biopsy. The event is defined as increase in size of prior sites of disease or evidence of new sites of disease, documented or not by biopsy. Relapse is adjudicated by ERC. Disease relapse is analyzed using cumulative incidence function with death as a competing risk. The analyses of this endpoint use the transplanted populations, and the time will be measured from transplant to the earliest of death, relapse/progression, or last follow up. |
| Percentage of Participants With Neutrophil Engraftment | Day 28 | Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) ≥ 500/mm\^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery. The competing event is death without neutrophil recovery. |
| Percentage of Participants With Platelet Recovery | Day 60 | Platelet recovery is defined as the first day of a sustained platelet count \>20,000/mm\^3 with no platelet transfusion in the preceding seven days. The first day of sustained platelet count above this threshold will be designated the day of platelet engraftment. The competing event is death without platelet recovery. |
| Participants With Primary Graft Failure | Day 28 | Primary graft failure is defined as no neutrophil recovery to \> 500 cells/µL by Day 28 post HSCT. |
| Percentage of Participants With Secondary Graft Failure | 2 Years | Secondary graft failure will be assessed according to neutrophil count after initial hematologic recovery. Secondary graft failure is defined as initial neutrophil engraftment followed by subsequent decline in absolute neutrophil counts \< 500 cells/µL, unresponsive to growth factor therapy, but cannot be explained by disease relapse or medications. Secondary graft failure will be analyzed using cumulative incidence function with death as a competing risk. |
| Percentage of Participants With Acute GVHD | Day 100 | Cumulative incidences of grade II-IV and III-IV acute GVHD were determined. Death prior to acute GVHD is treated as the competing risk. Grading of acute GVHD was derived by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). The acute GVHD algorithm calculates the grade based on the organ (skin, GI and liver) stage and etiology/biopsy reported on the weekly GVHD form. 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. Grade 4 is the worst outcome. |
| Percentage of Participants With Overall Survival (OS) | 2 Years | OS is a key secondary endpoint, with explicit control of the type I error rate through a gatekeeper approach. Formal significance testing of OS between a CNI-free strategy and the control will be conducted if the corresponding CRFS comparison is significant. This OS comparison will be done using a Bonferroni adjusted significance level of 0.05/3 to account for three potential CNI-free comparisons to the control. Otherwise, survival analyses will be considered exploratory. Death from any cause is considered as event for this endpoint. Participant is censored if lost to follow up. |
| Participants Infected Post Transplant | 2 Years | All grade 2 and grade 3 infections, as defined by the BMT CTN Technical MOP, occurring post transplantation will be reported. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each intervention arm. |
| Percentage of Participants With Chronic GVHD | 2 Years | The cumulative incidence of chronic GVHD will be determined. Death prior to acute GVHD is treated as the competing risk. Data will be collected directly from providers and chart review 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 With Chronic GVHD-free Survival | 2 Years | The event for this endpoint includes moderate to severe chronic GVHD according to NIH consensus criteria global score, or death by any cause. |
| Participants With Grade ≥ 3 Toxicity | 2 Years | All grades ≥ 3 toxicities according to CTCAE, version 4 will be tabulated for each intervention arm. The number of unique patients is counted. |
| Incidence of Infections | 2 years | All grade 2 and grade 3 infections, as defined by the BMT CTN Technical MOP, occurring post transplantation will be reported. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each intervention arm. |
| Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | Baseline, Day 100, Day 180, 1 year, 2 years | HQL will be measured post-transplant using patient-reported survey SF36. The SF36 is a 36 item general assessment of health quality of life with eight components: Physical Functioning, Role Physical, Pain Index, General Health Perceptions, Vitality, Social Functioning, Role Emotional, Mental Health Index. Each domain is positively scored, indicating that higher scores are associated with positive outcome. The total score ranges from 0 to 100. This scale is being used in this protocol as a generic measure of quality of life. To facilitate comparison of results with published norms, the Physical Component Summary and Mental Component Summary are used as the outcome measures in summarizing the SF36 data. These summary scores are derived by multiplying the z-score for each scale by its respective physical or mental factor score coefficient and summing the products. Resulting scores are then transformed into Tscores (mean=50; standard deviation=10). The SF36 takes 6 minutes to complete. |
| Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | Baseline, Day 100, Day 180, 1 year, 2 years | The FACT-BMT is a 37 item scale comprised of a general core questionnaire, the FACT-G with a possible range of 0-108 points, that evaluates the health-related quality of life (HQL) of patients receiving treatment for cancer, and a specific module, BMT Concerns, that addresses disease and treatment-related questions specific to bone marrow transplant. The FACT-G consists of four subscales developed and normed in cancer patients: Physical Well-being, Social/Family Well-being, Emotional Wellbeing, and Functional Well-being. Each subscale is positively scored, with higher scores indicating better functioning. The FACT-BMT Trial Outcome Index, comprised of the physical well-being scale, the functional well-being scale and the BMT specific items, will be used as the outcome measure in summarizing the FACT-BMT data. The FACT-BMT takes 6 minutes to complete. The final score for FACT-BMT ranges from 0 to 196. Higher scores for the scales and subscales indicate better quality of life. |
| Health-Related Quality of Life (HQL) - MDASI | Baseline, Day 100, Day 180, 1 year, 2 years | HQL will be measured post-transplant using patient-reported survey MD Anderson Symptom Inventory (MDASI). The MDASI is a 19 item instrument that captures 13 symptoms (0=not present to 10=as bad as you can imagine) and 6 items measuring interference with life from 0 (did not interfere) to 10 (interfered completely). MDASI Tool questions are negatively scored - higher levels indicate more severe symptoms and levels of interference. Codelist for each question is from 0 to 10. Scoring is taking the mean of items, so the range is 0-10. Lower scores for the scales indicate better quality of life. It provides two summary scales: symptoms and interference. The MDASI takes less than 5 minutes to complete. |
| Health-Related Quality of Life (HQL) - PedsQL | Baseline, Day 100, Day 180, 1 year, 2 years | HQL will be measured post-transplant using patient-reported survey PedsQL. The PedsQL™ Stem Cell Transplant Module is a 46-item instrument that measures health-related quality of life in children and adolescents undergoing hematopoietic stem cell transplant and is developmentally appropriate for self-report in ages 8 through 18 years. The score ranges from 0 to 100 with higher scores associated with positive outcome. |
| Participants With Maximum Acute GVHD | Day 100 | Grading of acute GVHD was derived by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). The acute GVHD algorithm calculates the grade based on the organ (skin, GI and liver) stage and etiology/biopsy reported on the weekly GVHD form. Grade I aGVHD is defined as Skin stage of 1-2 and stage 0 for both GI and liver organs. Grade II aGVHD 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. Max acute GVHD by Day 100 was computed. |
Countries
United States
Participant flow
Recruitment details
The study opened to accrual on August 17, 2015. Thirty-two participating centers were activated for enrollment and two of those were closed earlier without any enrollment. The study closed accrual on June 4, 2018 with 346 participants enrolled from 26 centers. Among the randomized participants, 327 participants received a transplant. Within the 19 participants who did not receive a transplant, there were 10 withdrawals of consents, 5 deaths, and 4 lost to follow-ups.
Participants by arm
| Arm | Count |
|---|---|
| CD34 Selected Graft Mobilized CD34-selected Peripheral Blood Stem Cell graft
Following screening and enrollment, the donor of patients randomized to the CD34-selection arm will receive mobilization therapy with once daily Granulocyte Colony Stimulating Factor (G-CSF). Mobilization will begin on Day -5 prior to the patient's transplant date.
Leukapheresis will be performed on a continuous flow cell separator according to institutional standards and will commence on the morning of the fifth day of G-CSF treatment. The anti-coagulant used for the procedure will be acid citrate dextrose (ACD).
Decisions concerning the need for further product collection will be based on the known or projected enriched CD34+ cell content of the previously collected products.
Mobilized CD34-selected Peripheral Blood Stem Cell graft: Mobilized CD34-selected PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated. | 114 |
| Post-Transplant Cyclophosphamide Unmanipulated Bone Marrow Graft with Cyclophosphamide
Unmanipulated BM grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Cyclophosphamide: Mesna will be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide or administered per institutional standards. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of Mesna is equal to 80% of the total daily dose of cyclophosphamide.
Cyclophosphamide 50 mg/kg will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume). | 114 |
| Tacrolimus/Methotrexate Control Unmanipulated bone marrow graft with Tacrolimus/Methotrexate (Tac/MTX) GVHD prophylaxis. Tac will be maintained at therapeutic doses for a minimum of 90 days. Cyclosporine may be substituted for Tac if the patient is intolerant of tacrolimus or per institutional practice. MTX will be dosed at 10-15mg/m\^2 for a maximum of 4 doses post-transplant.
Tac will be given orally or intravenously per institutional standards starting Day -3. The dose of Tac may be rounded to the nearest 0.5 mg for oral formulations. Subsequent dosing will be based on blood levels, with a target of 5-15 ng/ml. If patients are on medications which alter the metabolism of Tac (e.g. azoles), the initial starting dose and subsequent doses should be altered as per institutional practices. Tac taper can be initiated at a minimum of 90 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.
MTX will be administered at the doses of 15 mg/m\^2 IV bolus on Day +1, and 10 mg/m\^2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +1 dose of MTX should be given at least 24 hours after the hematopoietic stem cell infusion. Dose reduction of MTX due to worsening creatinine clearance after initiation of conditioning regimen, high serum levels or development of oral mucositis is allowed according to institutional practices. | 118 |
| Total | 346 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 3 | 2 |
| Overall Study | Not transplanted | 10 | 5 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Post-Transplant Cyclophosphamide | Tacrolimus/Methotrexate Control | CD34 Selected Graft | Total |
|---|---|---|---|---|
| Age, Continuous | 50.9 years | 51.3 years | 51.2 years | 51.1 years |
| Age, Customized 1-18 | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Age, Customized 19-40 | 28 Participants | 28 Participants | 29 Participants | 85 Participants |
| Age, Customized 41-60 | 69 Participants | 76 Participants | 63 Participants | 208 Participants |
| Age, Customized >60 | 17 Participants | 12 Participants | 22 Participants | 51 Participants |
| Cytogenetic Favorable | 12 Participants | 12 Participants | 13 Participants | 37 Participants |
| Cytogenetic Intermediate | 54 Participants | 56 Participants | 50 Participants | 160 Participants |
| Cytogenetic Missing | 8 Participants | 6 Participants | 11 Participants | 25 Participants |
| Cytogenetic Normal | 2 Participants | 4 Participants | 5 Participants | 11 Participants |
| Cytogenetic Not tested | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Cytogenetic Poor | 38 Participants | 39 Participants | 35 Participants | 112 Participants |
| Disease Risk High | 39 Participants | 40 Participants | 36 Participants | 115 Participants |
| Disease Risk Missing/Unknown | 8 Participants | 7 Participants | 11 Participants | 26 Participants |
| Disease Risk Non-high | 67 Participants | 71 Participants | 67 Participants | 205 Participants |
| Disease Stage for AML and ALL 1st complete remission | 67 Participants | 75 Participants | 65 Participants | 207 Participants |
| Disease Stage for AML and ALL >= 2nd complete remission | 21 Participants | 15 Participants | 15 Participants | 51 Participants |
| Disease Stage for AML and ALL Missing | 7 Participants | 4 Participants | 9 Participants | 20 Participants |
| Disease Stage for AML and ALL Primary induction failure (PIF)/Untreated | 5 Participants | 3 Participants | 2 Participants | 10 Participants |
| Disease Stage for AML and ALL Relapse | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Donor CMV Status Negative | 55 Participants | 71 Participants | 73 Participants | 199 Participants |
| Donor CMV Status Positive | 53 Participants | 43 Participants | 31 Participants | 127 Participants |
| Donor CMV Status Unknown | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Donor type Related Donor | 43 Participants | 45 Participants | 43 Participants | 131 Participants |
| Donor type Unrelated Donor | 71 Participants | 73 Participants | 71 Participants | 215 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 7 Participants | 7 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 102 Participants | 107 Participants | 105 Participants | 314 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 4 Participants | 2 Participants | 11 Participants |
| HCT-comorbidity index 0 | 41 Participants | 44 Participants | 38 Participants | 123 Participants |
| HCT-comorbidity index 1-2 | 43 Participants | 49 Participants | 37 Participants | 129 Participants |
| HCT-comorbidity index 3 or greater | 25 Participants | 21 Participants | 29 Participants | 75 Participants |
| HLA matching 8/8 | 114 Participants | 118 Participants | 114 Participants | 346 Participants |
| Lansky/Karnofsky Performance Score 70-80 | 42 Participants | 57 Participants | 51 Participants | 150 Participants |
| Lansky/Karnofsky Performance Score 90-100 | 72 Participants | 61 Participants | 63 Participants | 196 Participants |
| Pre-Transplant CMV status Negative | 55 Participants | 57 Participants | 59 Participants | 171 Participants |
| Pre-Transplant CMV status Positive | 54 Participants | 57 Participants | 45 Participants | 156 Participants |
| Primary Disease Acute Lymphoblastic Leukemia (ALL) | 27 Participants | 23 Participants | 30 Participants | 80 Participants |
| Primary Disease Acute Myelogenous Leukemia (AML) | 74 Participants | 75 Participants | 63 Participants | 212 Participants |
| Primary Disease Acute Undifferentiated Leukemia | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Primary Disease Biphenotypic Leukemia | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Primary Disease Chronic Myelomonocytic Leukemia (CMML) | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Primary Disease Myelodysplastic Syndrome (MDS) | 11 Participants | 16 Participants | 19 Participants | 46 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 7 Participants | 2 Participants | 17 Participants |
| Race (NIH/OMB) White | 101 Participants | 104 Participants | 106 Participants | 311 Participants |
| Sex: Female, Male Female | 43 Participants | 54 Participants | 52 Participants | 149 Participants |
| Sex: Female, Male Male | 71 Participants | 64 Participants | 62 Participants | 197 Participants |
| Stem cell source Bone Marrow | 98 Participants | 102 Participants | 6 Participants | 206 Participants |
| Stem cell source Peripheral Blood | 11 Participants | 12 Participants | 98 Participants | 121 Participants |
| Time from diagnosis to transplantation | 4.7 months | 5.0 months | 5.6 months | 5.0 months |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 42 / 114 | 27 / 114 | 30 / 118 |
| other Total, other adverse events | 3 / 114 | 1 / 114 | 2 / 118 |
| serious Total, serious adverse events | 9 / 114 | 7 / 114 | 7 / 118 |
Outcome results
Primary
Chronic GVHD-free, Relapse-free Survival (CRFS) Probability
The primary endpoint of the trial is Chronic GVHD/Relapse-Free Survival (CRFS), treated as a time to event variable. An event for this time to event outcome is defined as moderate to severe chronic GVHD, disease relapse, or death by any cause. Participant will be censored if lost to follow up prior to 2 years. Time is from randomization to the event of moderate to severe chronic GVHD, disease relapse, death, last follow up, or 2 years, whichever comes first. The primary analysis is performed using the intent-to-treat principle (ITT) so that all randomized patients are included in the analysis.
Time frame: 2 years
Population: All randomized patients are analyzed for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD34 Selected Graft | Chronic GVHD-free, Relapse-free Survival (CRFS) Probability | 1 year Post Randomization | 60.2 percentage of participants |
| CD34 Selected Graft | Chronic GVHD-free, Relapse-free Survival (CRFS) Probability | 2 years Post Randomization | 50.6 percentage of participants |
| Post-Transplant Cyclophosphamide | Chronic GVHD-free, Relapse-free Survival (CRFS) Probability | 1 year Post Randomization | 60.3 percentage of participants |
| Post-Transplant Cyclophosphamide | Chronic GVHD-free, Relapse-free Survival (CRFS) Probability | 2 years Post Randomization | 48.1 percentage of participants |
| Tacrolimus/Methotrexate Control | Chronic GVHD-free, Relapse-free Survival (CRFS) Probability | 1 year Post Randomization | 52.6 percentage of participants |
| Tacrolimus/Methotrexate Control | Chronic GVHD-free, Relapse-free Survival (CRFS) Probability | 2 years Post Randomization | 41.0 percentage of participants |
Comparison: The primary null hypothesis of the study is that there is no difference of the CRFS hazard ratio between CD34 select graft vs. Tac/MTX Control. The data in primary outcome table provides point estimates at specific time points (1 year and 2 years post randomization). The statistics in this session provides comparisons between different arms for the entire period of the study.p-value: 0.236895% CI: [0.562, 1.154]Log Rank
Comparison: The primary null hypothesis of the study is that there is no difference of the CRFS hazard ratio between Post-Transplant Cyclophosphamide vs. Tac/MTX Control. The data in primary outcome table provides point estimates. The statistics in this session provides comparisons between different arms for the entire period of the study.p-value: 0.413495% CI: [0.609, 1.228]Log Rank
Comparison: The primary null hypothesis of the study is that there is no difference of the CRFS hazard ratio between CD34 select graft vs. Post-Transplant Cyclophosphamide. The data in primary outcome table provides point estimates. The statistics in this session provides comparisons between different arms for the entire period of the study.p-value: 0.716695% CI: [0.643, 1.355]Log Rank
Comparison: The null hypothesis is that there is no difference of the CRFS hazard ratio between treatment groups after adjustment for age, donor type, performance status, primary disease, and disease risk. The data in primary outcome table provides point estimates. The statistics in this session provides comparisons between different arms for the entire period of the study.p-value: 0.386Regression, Cox
Comparison: Subgroup analyses are conducted for CRFS according to disease, disease risk and age. Interaction tests between treatment group and subgroup are conducted within a Cox proportional hazards regression model with treatment, subgroup, and a treatment\*subgroup interaction term. The null hypothesis is that there is no Interaction between treatment group and disease risk (Low/Intermediate vs. High) for CRFS.p-value: 0.461Cox proportional hazards regression
Comparison: Subgroup analyses are conducted for CRFS according to disease, disease risk and age. Interaction tests between treatment group and subgroup are conducted within a Cox proportional hazards regression model with treatment, subgroup, and a treatment\*subgroup interaction term. The null hypothesis is that there is no Interaction between treatment group and Age (\<=50 vs. \>50) for CRFS.p-value: 0.115Cox proportional hazards regression
Comparison: Subgroup analyses are conducted for CRFS according to disease, disease risk and age. Interaction tests between treatment group and subgroup are conducted within a Cox proportional hazards regression model with treatment, subgroup, and a treatment\*subgroup interaction term. The null hypothesis is that there is no Interaction between treatment group and Disease (AML vs. ALL vs. MDS) for CRFS.p-value: 0.227Cox proportional hazards regression
Secondary
Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT)
The FACT-BMT is a 37 item scale comprised of a general core questionnaire, the FACT-G with a possible range of 0-108 points, that evaluates the health-related quality of life (HQL) of patients receiving treatment for cancer, and a specific module, BMT Concerns, that addresses disease and treatment-related questions specific to bone marrow transplant. The FACT-G consists of four subscales developed and normed in cancer patients: Physical Well-being, Social/Family Well-being, Emotional Wellbeing, and Functional Well-being. Each subscale is positively scored, with higher scores indicating better functioning. The FACT-BMT Trial Outcome Index, comprised of the physical well-being scale, the functional well-being scale and the BMT specific items, will be used as the outcome measure in summarizing the FACT-BMT data. The FACT-BMT takes 6 minutes to complete. The final score for FACT-BMT ranges from 0 to 196. Higher scores for the scales and subscales indicate better quality of life.
Time frame: Baseline, Day 100, Day 180, 1 year, 2 years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at 1 Year | 73 score on a scale | Standard Error 1.9 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at Day 180 | 80 score on a scale | Standard Error 1.9 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at Day 100 | 63 score on a scale | Standard Error 1.9 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at Baseline | 67 score on a scale | Standard Error 1.6 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at 1 Year | 84 score on a scale | Standard Error 2.1 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at 1 Year | 114 score on a scale | Standard Error 2.8 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at 2 Years | 87 score on a scale | Standard Error 2.5 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at Day 180 | 108 score on a scale | Standard Error 2.5 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at 2 Years | 73 score on a scale | Standard Error 2.3 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at Day 100 | 106 score on a scale | Standard Error 2.4 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at Baseline | 81 score on a scale | Standard Error 1.6 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at Day 180 | 67 score on a scale | Standard Error 1.8 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at Baseline | 109 score on a scale | Standard Error 2.1 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at Day 100 | 79 score on a scale | Standard Error 1.7 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at 2 Years | 117 score on a scale | Standard Error 3.4 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at Day 180 | 83 score on a scale | Standard Error 1.7 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at Day 180 | 112 score on a scale | Standard Error 2.3 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at 1 Year | 116 score on a scale | Standard Error 2.6 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at 2 Years | 115 score on a scale | Standard Error 2.8 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at Baseline | 79 score on a scale | Standard Error 1.4 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at Day 100 | 80 score on a scale | Standard Error 1.5 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at 1 Year | 86 score on a scale | Standard Error 2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at 2 Years | 86 score on a scale | Standard Error 2.1 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at Baseline | 67 score on a scale | Standard Error 1.3 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at Day 100 | 66 score on a scale | Standard Error 1.5 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at 1 Year | 72 score on a scale | Standard Error 2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at 2 Years | 73 score on a scale | Standard Error 2.1 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at Baseline | 108 score on a scale | Standard Error 1.8 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at Day 100 | 108 score on a scale | Standard Error 2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at Day 180 | 69 score on a scale | Standard Error 1.8 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at Day 100 | 63 score on a scale | Standard Error 1.6 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at Day 180 | 67 score on a scale | Standard Error 1.5 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at Day 100 | 79 score on a scale | Standard Error 1.6 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at Day 180 | 110 score on a scale | Standard Error 2.1 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at 1 Year | 69 score on a scale | Standard Error 1.7 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at 1 Year | 113 score on a scale | Standard Error 2.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at 2 Years | 71 score on a scale | Standard Error 2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at 1 Year | 84 score on a scale | Standard Error 1.7 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at Baseline | 80 score on a scale | Standard Error 1.9 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at 2 Years | 84 score on a scale | Standard Error 2.1 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-G Total at Day 180 | 82 score on a scale | Standard Error 1.6 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at Baseline | 108 score on a scale | Standard Error 2.4 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Trial Outcome Index at Baseline | 65 score on a scale | Standard Error 1.8 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at Day 100 | 105 score on a scale | Standard Error 2.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT) | FACT-BMT Total at 2 Years | 113 score on a scale | Standard Error 2.7 |
Secondary
Health-Related Quality of Life (HQL) - MDASI
HQL will be measured post-transplant using patient-reported survey MD Anderson Symptom Inventory (MDASI). The MDASI is a 19 item instrument that captures 13 symptoms (0=not present to 10=as bad as you can imagine) and 6 items measuring interference with life from 0 (did not interfere) to 10 (interfered completely). MDASI Tool questions are negatively scored - higher levels indicate more severe symptoms and levels of interference. Codelist for each question is from 0 to 10. Scoring is taking the mean of items, so the range is 0-10. Lower scores for the scales indicate better quality of life. It provides two summary scales: symptoms and interference. The MDASI takes less than 5 minutes to complete.
Time frame: Baseline, Day 100, Day 180, 1 year, 2 years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at Day 100 | 2 score on a scale | Standard Error 0.2 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at Day 180 | 2 score on a scale | Standard Error 0.2 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at 1 Year | 2 score on a scale | Standard Error 0.2 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at 2 Years | 1 score on a scale | Standard Error 0.2 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Interference Score at Day 100 | 2 score on a scale | Standard Error 0.2 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at Baseline | 2 score on a scale | Standard Error 0.2 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Interference Score at Baseline | 2 score on a scale | Standard Error 0.2 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Interference Score at Day 180 | 2 score on a scale | Standard Error 0.3 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Interference Score at 1 Year | 2 score on a scale | Standard Error 0.3 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - MDASI | Interference Score at 2 Years | 1 score on a scale | Standard Error 0.3 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Interference Score at 1 Year | 2 score on a scale | Standard Error 0.3 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at Day 100 | 2 score on a scale | Standard Error 0.1 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at Baseline | 2 score on a scale | Standard Error 0.2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Interference Score at Baseline | 2 score on a scale | Standard Error 0.2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at Day 180 | 2 score on a scale | Standard Error 0.2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Interference Score at 2 Years | 2 score on a scale | Standard Error 0.3 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Interference Score at Day 180 | 2 score on a scale | Standard Error 0.3 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at 1 Year | 1 score on a scale | Standard Error 0.2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Interference Score at Day 100 | 2 score on a scale | Standard Error 0.2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at 2 Years | 2 score on a scale | Standard Error 0.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Interference Score at Day 180 | 2 score on a scale | Standard Error 0.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Interference Score at Baseline | 3 score on a scale | Standard Error 0.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at Baseline | 2 score on a scale | Standard Error 0.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at 2 Years | 2 score on a scale | Standard Error 0.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Interference Score at 1 Year | 2 score on a scale | Standard Error 0.3 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Interference Score at Day 100 | 2 score on a scale | Standard Error 0.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at Day 100 | 2 score on a scale | Standard Error 0.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Interference Score at 2 Years | 2 score on a scale | Standard Error 0.3 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at Day 180 | 2 score on a scale | Standard Error 0.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - MDASI | Symptoms Score at 1 Year | 2 score on a scale | Standard Error 0.2 |
Secondary
Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36)
HQL will be measured post-transplant using patient-reported survey SF36. The SF36 is a 36 item general assessment of health quality of life with eight components: Physical Functioning, Role Physical, Pain Index, General Health Perceptions, Vitality, Social Functioning, Role Emotional, Mental Health Index. Each domain is positively scored, indicating that higher scores are associated with positive outcome. The total score ranges from 0 to 100. This scale is being used in this protocol as a generic measure of quality of life. To facilitate comparison of results with published norms, the Physical Component Summary and Mental Component Summary are used as the outcome measures in summarizing the SF36 data. These summary scores are derived by multiplying the z-score for each scale by its respective physical or mental factor score coefficient and summing the products. Resulting scores are then transformed into Tscores (mean=50; standard deviation=10). The SF36 takes 6 minutes to complete.
Time frame: Baseline, Day 100, Day 180, 1 year, 2 years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at Baseline | 48 score on a scale | Standard Error 1 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at Day 100 | 48 score on a scale | Standard Error 1 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at Day 180 | 50 score on a scale | Standard Error 1.1 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at 1 year | 50 score on a scale | Standard Error 1.2 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at 2 years | 50 score on a scale | Standard Error 1.5 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at Baseline | 42 score on a scale | Standard Error 1 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at Day 100 | 40 score on a scale | Standard Error 1.1 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at Day 180 | 43 score on a scale | Standard Error 1.1 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at 1 year | 46 score on a scale | Standard Error 1.2 |
| CD34 Selected Graft | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at 2 years | 46 score on a scale | Standard Error 1.4 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at 1 year | 47 score on a scale | Standard Error 1.2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at Baseline | 46 score on a scale | Standard Error 1.2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at Baseline | 44 score on a scale | Standard Error 1 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at 2 years | 50 score on a scale | Standard Error 1.5 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at Day 100 | 48 score on a scale | Standard Error 1.1 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at 2 years | 47 score on a scale | Standard Error 1.2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at Day 180 | 44 score on a scale | Standard Error 1.2 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at Day 180 | 50 score on a scale | Standard Error 1.1 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at Day 100 | 41 score on a scale | Standard Error 1.1 |
| Post-Transplant Cyclophosphamide | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at 1 year | 52 score on a scale | Standard Error 1.1 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at Day 180 | 44 score on a scale | Standard Error 0.9 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at 1 year | 49 score on a scale | Standard Error 1.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at 2 years | 51 score on a scale | Standard Error 1.1 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at Baseline | 41 score on a scale | Standard Error 1.2 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at 1 year | 44 score on a scale | Standard Error 1.1 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at Day 100 | 40 score on a scale | Standard Error 1 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at Baseline | 48 score on a scale | Standard Error 1.1 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED PHYSICAL COMPONENT SCALE at 2 years | 47 score on a scale | Standard Error 1.3 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at Day 100 | 48 score on a scale | Standard Error 1 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - Medical Outcomes Study Short Form 36 (SF36) | STANDARDIZED MENTAL COMPONENT SCALE at Day 180 | 49 score on a scale | Standard Error 0.9 |
Secondary
Health-Related Quality of Life (HQL) - PedsQL
HQL will be measured post-transplant using patient-reported survey PedsQL. The PedsQL™ Stem Cell Transplant Module is a 46-item instrument that measures health-related quality of life in children and adolescents undergoing hematopoietic stem cell transplant and is developmentally appropriate for self-report in ages 8 through 18 years. The score ranges from 0 to 100 with higher scores associated with positive outcome.
Time frame: Baseline, Day 100, Day 180, 1 year, 2 years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - PedsQL | Pediatric Quality of Life Score at Baseline | 80.18 score on a scale | Standard Error 14.94 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - PedsQL | Pediatric Quality of Life Score at Day 100 | 69.82 score on a scale | Standard Error 2.75 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - PedsQL | Pediatric Quality of Life Score at Day 180 | 72.56 score on a scale | Standard Error 3.05 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - PedsQL | Pediatric Quality of Life Score at 1 Year | 78.05 score on a scale | Standard Error 4.27 |
| Tacrolimus/Methotrexate Control | Health-Related Quality of Life (HQL) - PedsQL | Pediatric Quality of Life Score at 2 Years | 53.66 score on a scale | Standard Error 21.34 |
Secondary
Incidence of Infections
All grade 2 and grade 3 infections, as defined by the BMT CTN Technical MOP, occurring post transplantation will be reported. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each intervention arm.
Time frame: 2 years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD34 Selected Graft | Incidence of Infections | 157 number of Infection Events |
| Post-Transplant Cyclophosphamide | Incidence of Infections | 161 number of Infection Events |
| Tacrolimus/Methotrexate Control | Incidence of Infections | 123 number of Infection Events |
Secondary
Participants Infected Post Transplant
All grade 2 and grade 3 infections, as defined by the BMT CTN Technical MOP, occurring post transplantation will be reported. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each intervention arm.
Time frame: 2 Years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CD34 Selected Graft | Participants Infected Post Transplant | Patients with Grades 2-3 infections | 72 Participants |
| CD34 Selected Graft | Participants Infected Post Transplant | Patients with Grades 3 infections | 31 Participants |
| Post-Transplant Cyclophosphamide | Participants Infected Post Transplant | Patients with Grades 2-3 infections | 66 Participants |
| Post-Transplant Cyclophosphamide | Participants Infected Post Transplant | Patients with Grades 3 infections | 23 Participants |
| Tacrolimus/Methotrexate Control | Participants Infected Post Transplant | Patients with Grades 3 infections | 16 Participants |
| Tacrolimus/Methotrexate Control | Participants Infected Post Transplant | Patients with Grades 2-3 infections | 50 Participants |
Comparison: The null hypothesis is that there is no difference of Grades II-III infection post-transplantation between the treatment groups.p-value: 0.0006Gray's test for cumulative Incidence
Comparison: The null hypothesis is that there is no difference of Grades III infection post-transplantation between the treatment groups.p-value: 0.0145Gray's test for cumulative Incidence
Secondary
Participants With Grade ≥ 3 Toxicity
All grades ≥ 3 toxicities according to CTCAE, version 4 will be tabulated for each intervention arm. The number of unique patients is counted.
Time frame: 2 Years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Overall NCI CTCAE Grade 3-5 Toxicities | 80 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-4 Alkaline Phosphatase | 11 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Somnolence | 7 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Any Grade 3-5 Stem Cell Infusional Toxicities | 6 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-4 Bilirubin | 8 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Seizure | 6 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Chronic kidney disease | 4 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-4 AST | 11 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Thrombotic thrombocytopenic purpura | 1 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Toxicities 1 year to 2 years | 23 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-4 ALT | 10 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Capillary leak syndrome | 1 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Toxicities Within Day 100 | 68 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Dsypnea | 23 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hypoxia | 32 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hemorrhage | 12 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Cystitis noninfective | 4 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | IPS | 2 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hypotension | 19 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Oral mucositis | 39 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | SOS/VOD | 0 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hypertension | 20 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Toxicities Day 100 to 1 year | 26 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Abnormal liver function | 12 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Cardiac arrhythmia | 9 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Acute kidney injury | 12 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Received dialysis | 5 Participants |
| CD34 Selected Graft | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Left ventricular systolic dysfunction | 5 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Toxicities Within Day 100 | 82 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Any Grade 3-5 Stem Cell Infusional Toxicities | 4 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Oral mucositis | 51 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Cystitis noninfective | 11 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Acute kidney injury | 13 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Chronic kidney disease | 4 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hemorrhage | 9 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hypotension | 15 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hypertension | 21 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Cardiac arrhythmia | 6 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Left ventricular systolic dysfunction | 2 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Somnolence | 4 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Seizure | 0 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Thrombotic thrombocytopenic purpura | 2 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Capillary leak syndrome | 0 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hypoxia | 22 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Dsypnea | 15 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-4 ALT | 26 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-4 AST | 27 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-4 Bilirubin | 14 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Grades 3-4 Alkaline Phosphatase | 12 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Received dialysis | 2 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Abnormal liver function | 14 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | SOS/VOD | 2 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | IPS | 2 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Toxicities Day 100 to 1 year | 33 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Toxicities 1 year to 2 years | 18 Participants |
| Post-Transplant Cyclophosphamide | Participants With Grade ≥ 3 Toxicity | Overall NCI CTCAE Grade 3-5 Toxicities | 88 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-4 Bilirubin | 7 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Left ventricular systolic dysfunction | 8 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Any Grade 3-5 Stem Cell Infusional Toxicities | 17 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-4 Alkaline Phosphatase | 6 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Cardiac arrhythmia | 8 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Toxicities Day 100 to 1 year | 41 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Received dialysis | 6 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hypertension | 30 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Oral mucositis | 63 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Abnormal liver function | 24 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hypotension | 11 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Overall NCI CTCAE Grade 3-5 Toxicities | 100 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | SOS/VOD | 1 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hemorrhage | 4 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Toxicities 1 year to 2 years | 24 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | IPS | 3 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Hypoxia | 14 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Capillary leak syndrome | 1 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Chronic kidney disease | 3 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Dsypnea | 12 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Thrombotic thrombocytopenic purpura | 4 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Acute kidney injury | 15 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-4 ALT | 18 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Seizure | 2 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Toxicities Within Day 100 | 81 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-4 AST | 19 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Somnolence | 4 Participants |
| Tacrolimus/Methotrexate Control | Participants With Grade ≥ 3 Toxicity | Grades 3-5 Cystitis noninfective | 2 Participants |
Secondary
Participants With Immunosuppression-free Survival
Patients who are alive, relapse-free, and do not need ongoing immune suppression to control GVHD at one year post HSCT are considered successes for this endpoint. Immune suppression is defined as any systemic agents used to control or suppress GVHD.
Time frame: 1 Year
Population: The analyses of this endpoint will use the transplanted populations. Two participant of CD34 Selected Graft arm and one participants of Post-Transplant Cyclophosphamide arm were lost to follow-up while alive and not relapsed, and they are considered as not evaluable for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CD34 Selected Graft | Participants With Immunosuppression-free Survival | 59 Participants |
| Post-Transplant Cyclophosphamide | Participants With Immunosuppression-free Survival | 73 Participants |
| Tacrolimus/Methotrexate Control | Participants With Immunosuppression-free Survival | 66 Participants |
Comparison: The null hypothesis is that there is no difference of immunosuppression-free survival at 1-year post-transplant between the treatment groups.p-value: 0.2389Chi-squared
Comparison: The null hypothesis is that there is no agreement between CRFS and immunosuppression-free survival at 1-year post-transplant.p-value: <0.0001Cohen's Kappa
Secondary
Participants With Maximum Acute GVHD
Grading of acute GVHD was derived by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). The acute GVHD algorithm calculates the grade based on the organ (skin, GI and liver) stage and etiology/biopsy reported on the weekly GVHD form. Grade I aGVHD is defined as Skin stage of 1-2 and stage 0 for both GI and liver organs. Grade II aGVHD 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. Max acute GVHD by Day 100 was computed.
Time frame: Day 100
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CD34 Selected Graft | Participants With Maximum Acute GVHD | Grade III | 3 Participants |
| CD34 Selected Graft | Participants With Maximum Acute GVHD | Grade II | 14 Participants |
| CD34 Selected Graft | Participants With Maximum Acute GVHD | Grade 0, No aGVHD | 72 Participants |
| CD34 Selected Graft | Participants With Maximum Acute GVHD | Grade I | 15 Participants |
| CD34 Selected Graft | Participants With Maximum Acute GVHD | Grade IV | 0 Participants |
| Post-Transplant Cyclophosphamide | Participants With Maximum Acute GVHD | Grade II | 30 Participants |
| Post-Transplant Cyclophosphamide | Participants With Maximum Acute GVHD | Grade 0, No aGVHD | 45 Participants |
| Post-Transplant Cyclophosphamide | Participants With Maximum Acute GVHD | Grade I | 23 Participants |
| Post-Transplant Cyclophosphamide | Participants With Maximum Acute GVHD | Grade III | 9 Participants |
| Post-Transplant Cyclophosphamide | Participants With Maximum Acute GVHD | Grade IV | 2 Participants |
| Tacrolimus/Methotrexate Control | Participants With Maximum Acute GVHD | Grade IV | 0 Participants |
| Tacrolimus/Methotrexate Control | Participants With Maximum Acute GVHD | Grade III | 4 Participants |
| Tacrolimus/Methotrexate Control | Participants With Maximum Acute GVHD | Grade 0, No aGVHD | 55 Participants |
| Tacrolimus/Methotrexate Control | Participants With Maximum Acute GVHD | Grade II | 30 Participants |
| Tacrolimus/Methotrexate Control | Participants With Maximum Acute GVHD | Grade I | 25 Participants |
Secondary
Participants With Primary Graft Failure
Primary graft failure is defined as no neutrophil recovery to \> 500 cells/µL by Day 28 post HSCT.
Time frame: Day 28
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CD34 Selected Graft | Participants With Primary Graft Failure | 3 Participants |
| Post-Transplant Cyclophosphamide | Participants With Primary Graft Failure | 9 Participants |
| Tacrolimus/Methotrexate Control | Participants With Primary Graft Failure | 4 Participants |
Secondary
Percentage of Participants With Acute GVHD
Cumulative incidences of grade II-IV and III-IV acute GVHD were determined. Death prior to acute GVHD is treated as the competing risk. Grading of acute GVHD was derived by consensus grading (Przepiorka 1995) per BMTCTN manual of procedures (MOP). The acute GVHD algorithm calculates the grade based on the organ (skin, GI and liver) stage and etiology/biopsy reported on the weekly GVHD form. 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. Grade 4 is the worst outcome.
Time frame: Day 100
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Acute GVHD | grade III-IV acute GVHD | 2.9 percentage of participants |
| CD34 Selected Graft | Percentage of Participants With Acute GVHD | grade II-IV acute GVHD | 16.3 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Acute GVHD | grade III-IV acute GVHD | 10.1 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Acute GVHD | grade II-IV acute GVHD | 37.6 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Acute GVHD | grade II-IV acute GVHD | 29.8 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Acute GVHD | grade III-IV acute GVHD | 3.5 percentage of participants |
Comparison: The null hypothesis is that there is no difference of grade II-IV acute GVHD post-transplantation between the treatment groups.p-value: 0.0026Gray's test for cumulative Incidence
Comparison: The null hypothesis is that there is no difference of grade III-IV acute GVHD post-transplantation between the treatment groups.p-value: 0.0369Gray's test for cumulative Incidence
Comparison: The null hypothesis is that there is no difference of the grade II-IV acute GVHD hazard ratio between treatment groups after adjustment for age, donor type, performance status, primary disease, and disease risk.p-value: 0.002Regression, Cox
Comparison: The null hypothesis is that there is no difference of the grade III-IV acute GVHD hazard ratio between treatment groups after adjustment for age, donor type, performance status, primary disease, and disease risk.p-value: 0.046Regression, Cox
Secondary
Percentage of Participants With Chronic GVHD
The cumulative incidence of chronic GVHD will be determined. Death prior to acute GVHD is treated as the competing risk. Data will be collected directly from providers and chart review 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.
Time frame: 2 Years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Chronic GVHD | 1 year post-transplantation | 16.4 percentage of participants |
| CD34 Selected Graft | Percentage of Participants With Chronic GVHD | 2 years post-transplantation | 18.5 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Chronic GVHD | 1 year post-transplantation | 33.0 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Chronic GVHD | 2 years post-transplantation | 37.0 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Chronic GVHD | 1 year post-transplantation | 31.1 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Chronic GVHD | 2 years post-transplantation | 40.0 percentage of participants |
Comparison: The null hypothesis is that there is no difference of chronic GVHD post-transplantation between the treatment groups.p-value: 0.0024Gray's test for cumulative Incidence
Comparison: The null hypothesis is that there is no difference of the chronic GVHD hazard ratio between treatment groups after adjustment for age, donor type, performance status, primary disease, and disease risk.p-value: 0.005Regression, Cox
Secondary
Percentage of Participants With Chronic GVHD-free Survival
The event for this endpoint includes moderate to severe chronic GVHD according to NIH consensus criteria global score, or death by any cause.
Time frame: 2 Years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Chronic GVHD-free Survival | 1 year post-transplantation | 71.0 percentage of participants |
| CD34 Selected Graft | Percentage of Participants With Chronic GVHD-free Survival | 2 years post-transplantation | 55.4 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Chronic GVHD-free Survival | 1 year post-transplantation | 67.4 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Chronic GVHD-free Survival | 2 years post-transplantation | 54.2 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Chronic GVHD-free Survival | 1 year post-transplantation | 65.8 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Chronic GVHD-free Survival | 2 years post-transplantation | 47.1 percentage of participants |
Comparison: The null hypothesis is that there is no difference of Chronic GVHD-free Survival post-transplantation between the treatment groups.p-value: 0.229Log Rank
Secondary
Percentage of Participants With Disease Relapse
Relapse is defined by either morphological evidence of acute leukemia or MDS consistent with pre-transplant features, or radiologic evidence of lymphoma, documented or not by biopsy. The event is defined as increase in size of prior sites of disease or evidence of new sites of disease, documented or not by biopsy. Relapse is adjudicated by ERC. Disease relapse is analyzed using cumulative incidence function with death as a competing risk. The analyses of this endpoint use the transplanted populations, and the time will be measured from transplant to the earliest of death, relapse/progression, or last follow up.
Time frame: 2 Years
Population: The analyses of this endpoint use the transplanted populations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Disease Relapse | 1 year post transplantation | 19.4 percentage of participants |
| CD34 Selected Graft | Percentage of Participants With Disease Relapse | 2 years post transplantation | 21.4 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Disease Relapse | 1 year post transplantation | 9.2 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Disease Relapse | 2 years post transplantation | 13.9 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Disease Relapse | 1 year post transplantation | 22.9 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Disease Relapse | 2 years post transplantation | 25.6 percentage of participants |
Comparison: The null hypothesis is that there is no difference of Disease Relapse between the treatment groups.p-value: 0.076Gray's test for cumulative Incidence
Comparison: The null hypothesis is that there is no difference of the Disease Relapse hazard ratio between treatment groups after adjustment for age, donor type, performance status, primary disease, and disease risk.p-value: 0.106Regression, Cox
Secondary
Percentage of Participants With Neutrophil Engraftment
Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) ≥ 500/mm\^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery. The competing event is death without neutrophil recovery.
Time frame: Day 28
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Neutrophil Engraftment | 97.1 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Neutrophil Engraftment | 91.7 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Neutrophil Engraftment | 96.5 percentage of participants |
Comparison: The null hypothesis is that there is no difference of Neutrophil Engraftment post-transplantation between the treatment groups.p-value: 0.0764Gray's test for cumulative Incidence
Secondary
Percentage of Participants With Overall Survival (OS)
OS is a key secondary endpoint, with explicit control of the type I error rate through a gatekeeper approach. Formal significance testing of OS between a CNI-free strategy and the control will be conducted if the corresponding CRFS comparison is significant. This OS comparison will be done using a Bonferroni adjusted significance level of 0.05/3 to account for three potential CNI-free comparisons to the control. Otherwise, survival analyses will be considered exploratory. Death from any cause is considered as event for this endpoint. Participant is censored if lost to follow up.
Time frame: 2 Years
Population: The randomized or transplanted participants are included in the analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Overall Survival (OS) | 1 year post-randomization | 75.7 percentage of participants |
| CD34 Selected Graft | Percentage of Participants With Overall Survival (OS) | 2 year post-randomization | 60.1 percentage of participants |
| CD34 Selected Graft | Percentage of Participants With Overall Survival (OS) | 1 year post-transplantation | 74.8 percentage of participants |
| CD34 Selected Graft | Percentage of Participants With Overall Survival (OS) | 2 year post-transplantation | 61.6 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Overall Survival (OS) | 2 year post-transplantation | 76.7 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Overall Survival (OS) | 1 year post-randomization | 84.6 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Overall Survival (OS) | 1 year post-transplantation | 83.4 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Overall Survival (OS) | 2 year post-randomization | 76.2 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Overall Survival (OS) | 2 year post-transplantation | 74.2 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Overall Survival (OS) | 2 year post-randomization | 76.1 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Overall Survival (OS) | 1 year post-transplantation | 83.3 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Overall Survival (OS) | 1 year post-randomization | 84.2 percentage of participants |
Comparison: The null hypothesis is that there is no difference of the OS hazard ratio between CD34 select graft vs. Tac/MTX Control.p-value: 0.019795% CI: [1.086, 2.8]Log Rank
Comparison: The null hypothesis is that there is no difference of the OS hazard ratio between Post-Transplant Cyclophosphamide vs. Tac/MTX Control.p-value: 0.952595% CI: [0.599, 1.724]Log Rank
Comparison: The null hypothesis is that there is no difference of the OS hazard ratio between CD34 select graft vs. Post-Transplant Cyclophosphamide.p-value: 0.018595% CI: [1.093, 2.877]Log Rank
Comparison: The null hypothesis is that there is no difference of the OS hazard ratio between treatment groups after adjustment for age, donor type, performance status, primary disease, and disease risk.p-value: 0.026Regression, Cox
Secondary
Percentage of Participants With Platelet Recovery
Platelet recovery is defined as the first day of a sustained platelet count \>20,000/mm\^3 with no platelet transfusion in the preceding seven days. The first day of sustained platelet count above this threshold will be designated the day of platelet engraftment. The competing event is death without platelet recovery.
Time frame: Day 60
Population: The analyses of the endpoint use the transplanted populations. Three transplanted participants (one from the CD34 arm and two from the PTCy arm) are missing platelet data and are not included in the analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Platelet Recovery | 94.2 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Platelet Recovery | 91.6 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Platelet Recovery | 98.2 percentage of participants |
Comparison: The null hypothesis is that there is no difference of Platelet recovery post-transplantation between the treatment groups.p-value: 0.0001Gray's test for cumulative Incidence
Secondary
Percentage of Participants With Relapse-free Survival
The events for this endpoint RFS are death and relapse of the underlying malignancy. The analyses of this endpoint use the transplanted populations and time is from transplant to the event of disease relapse or death, or last follow up, whichever comes first.
Time frame: 2 Years
Population: The analyses of this endpoint will use the transplanted population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Relapse-free Survival | 1 year post-transplantation | 64.1 percentage of participants |
| CD34 Selected Graft | Percentage of Participants With Relapse-free Survival | 2 years post-transplantation | 57.1 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Relapse-free Survival | 1 year post-transplantation | 78.8 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Relapse-free Survival | 2 years post-transplantation | 70.3 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Relapse-free Survival | 1 year post-transplantation | 70.1 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Relapse-free Survival | 2 years post-transplantation | 66.5 percentage of participants |
Comparison: The null hypothesis is that there is no difference of Relapse-Free Survival between the treatment groups.p-value: 0.029Log Rank
Comparison: The null hypothesis is that there is no difference of the RFS hazard ratio between treatment groups after adjustment for age, donor type, performance status, primary disease, and disease risk.p-value: 0.145Regression, Cox
Secondary
Percentage of Participants With Secondary Graft Failure
Secondary graft failure will be assessed according to neutrophil count after initial hematologic recovery. Secondary graft failure is defined as initial neutrophil engraftment followed by subsequent decline in absolute neutrophil counts \< 500 cells/µL, unresponsive to growth factor therapy, but cannot be explained by disease relapse or medications. Secondary graft failure will be analyzed using cumulative incidence function with death as a competing risk.
Time frame: 2 Years
Population: The analyses of the endpoint use the transplanted populations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Secondary Graft Failure | 2.9 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Secondary Graft Failure | 0 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Secondary Graft Failure | 0.9 percentage of participants |
Comparison: The null hypothesis is that there is no difference of Secondary graft failure post-transplantation between the treatment groups.p-value: 0.1478Gray's test for cumulative Incidence
Secondary
Percentage of Participants With Treatment-related Mortality
The events for this endpoint TRM are deaths prior to relapse of the underlying malignancy. The analyses of this endpoint will use the transplanted populations, and time will be from transplant to the first of disease relapse, death, or last follow up. TRM are evaluated using the cumulative incidence function. Deaths without relapse are the events for this endpoint and relapse is a competing risk for this endpoint.
Time frame: 2 Years
Population: The analyses of this endpoint will use the transplanted populations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CD34 Selected Graft | Percentage of Participants With Treatment-related Mortality | 1 year post-transplantation | 16.5 percentage of participants |
| CD34 Selected Graft | Percentage of Participants With Treatment-related Mortality | 2 years post-transplantation | 21.5 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Treatment-related Mortality | 1 year post-transplantation | 12.0 percentage of participants |
| Post-Transplant Cyclophosphamide | Percentage of Participants With Treatment-related Mortality | 2 years post-transplantation | 15.7 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Treatment-related Mortality | 1 year post-transplantation | 7.0 percentage of participants |
| Tacrolimus/Methotrexate Control | Percentage of Participants With Treatment-related Mortality | 2 years post-transplantation | 7.9 percentage of participants |
Comparison: The null hypothesis is that there is no difference of Transplant-Related Mortality between the treatment groups.p-value: 0.02Gray's test for cumulative Incidence
Comparison: The null hypothesis is that there is no difference of the TRM hazard ratio between treatment groups after adjustment for age, donor type, performance status, primary disease, and disease risk.p-value: 0.04Regression, Cox