Acute Biphenotypic Leukemia (ABL), Acute Lymphoblastic Leukemia (ALL)/T Lymphoblastic Lymphoma, Acute Myelogenous Leukemia (AML), Acute Undifferentiated Leukemia (AUL), Chemotherapy-sensitive Lymphoma, Chronic Lymphocytic Leukemia (CLL), Myelodysplastic Syndrome (MDS)
Conditions
Brief summary
This is a multi-center, single arm Phase II study of hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-mismatched unrelated bone marrow transplantation donors and post-transplantation cyclophosphamide (PTCy), sirolimus and mycophenolate mofetil (MMF) for graft versus host disease (GVHD) prophylaxis in patients with hematologic malignancies.
Interventions
DRUGG-CSF
Granulocyte-colony stimulating factor (G-CSF): filgrastim or a biosimilar begins on Day+5 at a dose of 5 mcg/kg/day (actual body weight) IV or subcutaneously (SC) (rounding to the nearest vial dose is allowed), until the absolute neutrophil count (ANC) is ≥ 1,000/mm3 over the course of 3 consecutive days. Additional G-CSF may be administered as warranted.
DRUGPre-HCT Mesna on Days -6 and -5
Use of Mesna and dosing will be done according to institutional standards. A recommended approach is as follows: Mesna IV dose of ≥ 80% of the total daily dose of Cy and given in divided doses 30 minutes before and at 3, 6, and 8-9 hours after completion of Cy. Mesna is dosed according to adjusted IBW (Appendix K), unless the subject weighs less than IBW, in which case Mesna will be dosed according to actual weight.
DRUGPre-HCT Mesna on Days -2 and -1
Use of Mesna and dosing will be done according to institutional standards. A recommended approach is as follows: Mesna IV dose of ≥ 80% of the total daily dose of Cy and given in divided doses 30 minutes before and at 3, 6, and 8-9 hours after completion of Cy. Mesna is dosed according to adjusted IBW (Appendix K), unless the subject weighs less than IBW, in which case Mesna will be dosed according to actual weight.
DRUGPre-HCT Mesna on Days -5 and -4
Use of Mesna and dosing will be done according to institutional standards. A recommended approach is as follows: Mesna IV dose of ≥ 80% of the total daily dose of Cy and given in divided doses 30 minutes before and at 3, 6, and 8-9 hours after completion of Cy. Mesna is dosed according to adjusted IBW (Appendix K), unless the subject weighs less than IBW, in which case Mesna will be dosed according to actual weight.
DRUGPost-HCT Mesna
Mesna is required. Mesna IV dose must be ≥ 80% of the total daily dose of Cy and given in divided doses 30 minutes before and at 3, 6, and 8-9 hours after completion of Cy on Day+3 and Day+4. Mesna is dosed according to IBW, unless the subject weighs less than IBW, in which case Mesna will be dosed according to actual body weight.
DRUGFludarabine
* Fludarabine 30 mg/m2/day (adjusted for renal function) is administered over a 30-60 minute IV infusion on Days -6 through -2 (maximum cumulative dose, 150 mg/m2). * The body surface area (BSA) for fludarabine dosing is based on adjusted ideal body weight (IBW) (Appendix K). * creatinine clearance may change during the days fludarabine is given. Adjustment in fludarabine dose due to creatinine changes during conditioning is permitted.
DRUGCyclophosphamide 14.5 mg/kg/day IV on Days -6, -5
* Cy 14.5 mg/kg/day is administered as a 1-2 hour IV infusion on Days -6 and -5 after hydration. * Use of Mesna and dosing will be done according to institutional standards. A recommended approach is as follows: Mesna IV dose of ≥ 80% of the total daily dose of Cy and given in divided doses 30 minutes before and at 3, 6, and 8-9 hours after completion of Cy. * Hydration prior to Cy may be given according to institutional guideline. * Cy and mesna are dosed according to adjusted IBW (Appendix K), unless the subject weighs less than IBW, in which case these drugs will be dosed according to actual weight.
RADIATIONTotal Body Irradiation (TBI) 200cGy on Day -1
* 200 cGy TBI is administered in a single fraction on Day -1. * Radiation sources, dose rates, and shielding follow institutional practice.
PROCEDUREInfusion of non-T-cell depleted bone marrow on Day 0
* On Day 0, the harvested bone marrow is infused. * Donor bone marrow will be harvested with a target yield of 4 x 108 nucleated cells/kg recipient weight. * The lowest acceptable nucleated cells yield is 1.5 x 108 cells/kg recipient weight.
DRUGBusulfan
* Busulfan ≥ 9mg/kg total dose (IV or PO) on Days -6, -5, -4, -3 (PK monitoring required to achieve a daily area under the curve (AUC) target of 4800-5300 μM\*min (Perkins et al., 2012)) * Busulfan dosing is based on adjusted IBW (Appendix K)
DRUGCyclophosphamide 50mg/kg/day IV on Days -2,-1
* Cy 50mg/kg/day is administered as a 1-2 hour IV infusion on Days -2 and -1 after hydration. * Use of Mesna and dosing will be done according to institutional standards. A recommended approach is as follows: Mesna IV dose of ≥ 80% of the total daily dose of Cy and given in divided doses 30 minutes before and at 3, 6, and 8-9 hours after completion of Cy. * Hydration prior to Cy may be given according to institutional guideline. * Cy and mesna are dosed according to adjusted IBW (Appendix K), unless the subject weighs less than IBW, in which case these drugs will be dosed according to actual weight.
DRUGCyclophosphamide 50mg/kg/day IV on Days -5,-4
* Cy 50mg/kg/day is administered as a 1-2 hour IV infusion on Days -5 and -4 after hydration. * Use of Mesna and dosing will be done according to institutional standards. A recommended approach is as follows: Mesna IV dose of ≥ 80% of the total daily dose of Cy and given in divided doses 30 minutes before and at 3, 6, and 8-9 hours after completion of Cy. * Hydration prior to Cy may be given according to institutional guideline. * Cy and mesna are dosed according to adjusted IBW (Appendix K), unless the subject weighs less than IBW, in which case these drugs will be dosed according to actual weight.
RADIATIONTotal Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1
* 200cGy TBI is administered in twice daily on Days -3, -2, and -1. * Radiation sources, dose rates, and shielding follow institutional practice.
DRUGPost-HCT Cyclophosphamide 50mg/kg IV on Day+3, +4
* Cy 50mg/kg IV, over 1-2 hours (depending on volume), is given on Day+3 (ideally between 60 and 72 hours after bone marrow infusion) and on Day+4 (approximately 24 hours after Day+3 Cy). * Hydration with Cy, management of volume status, and monitoring for hemorrhagic cystitis will follow institutional standards. * Mesna is required. Mesna IV dose must be ≥ 80% of the total daily dose of Cy and given in divided doses 30 minutes before and at 3, 6, and 8-9 hours after completion of Cy. * Cy is dosed according to IBW, unless the subject weighs less than IBW, in which case these drugs will be dosed according to actual body weight.
DRUGSirolimus
* Sirolimus dosing is based on adjusted IBW (Appendix K). * Sirolimus prophylaxis is discontinued after the last dose on Day+180, or may be continued if there is GVHD. For subjects ≥ 18 years old: * A one-time sirolimus loading dose, 6 mg PO, is given on Day+5, at least 24 hours after Cy completion. * Sirolimus is then continued at a maintenance dose (starting dose 2 mg PO QD), with dose adjustments to maintain a trough of 5 - 15 ng/mL as measured by high performance liquid chromatography (HPLC) or immunoassay. For subjects \< 18 years old: * A one-time sirolimus loading dose, 3 mg/m2 PO with the dose not to exceed 6 mg, is given on Day+5, at least 24 hours after Cy completion. * Sirolimus is then continued at a maintenance dose (starting dose 1 mg/m2 PO QD, maximum 2 mg PO QD), with dose adjustments to maintain a trough of 5 - 15 ng/mL as measured by HPLC or immunoassay.
DRUGMycophenolate mofetil
MMF begins on Day+5, at least 24 hours after completion of PTCy. MMF dose is 15 mg/kg PO TID (adjusted IBW (Appendix K)) with total daily dose not to exceed 3 grams (i.e. maximum 1 g PO TID). An equivalent IV dose (1:1 conversion) may instead be given. MMF prophylaxis is discontinued after the last dose on Day+35, or may be continued if there is GVHD.
Sponsors
National Marrow Donor Program
Center for International Blood and Marrow Transplant Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 15 years and \< 71 years at the time of signing the informed consent form 2. Partially HLA-mismatched unrelated donor: HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, -C, and -DRB1 loci; a minimum match of 4/8 at HLA-A, -B, -C, and -DRB1 is required 3. Product planned for infusion is bone marrow 4. Disease and disease status: 1. Acute Leukemias or T lymphoblastic lymphoma in 1st or subsequent complete remission (CR): Acute lymphoblastic leukemia (ALL)/T lymphoblastic lymphoma; acute myelogenous leukemia (AML); acute biphenotypic leukemia (ABL); acute undifferentiated leukemia (AUL) 2. Myelodysplastic Syndrome (MDS), fulfilling the following criteria: Subjects with de novo MDS who have or have previously had Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is not a requirement; Subjects must have \< 20% bone marrow blasts, assessed within 60 days of informed consent; Subjects may have received prior therapy for the treatment of MDS prior to enrollment 3. Chronic Lymphocytic Leukemia (CLL) in CR if RIC is to be used; in CR or partial response (PR) if FIC is to be used 4. Chronic myeloid leukemia (CML) in 1st or subsequent chronic phase characterized by \<10% blasts in the blood or bone marrow. 5. Chemotherapy-sensitive lymphoma in status other than 1st CR 5. Performance status: Karnofsky or Lansky score ≥ 60% (Appendix A) 6. Adequate organ function defined as: 1. Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 35% (RIC cohort) or LVEF at rest ≥ 40% (FIC cohort), or left ventricular shortening fraction (LVFS) ≥ 25% 2. Pulmonary: diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume (FEV1), forced vital capacity (FVC) ≥ 50% predicted by pulmonary function tests (PFTs) 3. Hepatic: total bilirubin ≤ 2.5 mg/dL, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) \< 5 x upper limit of (ULN) (unless disease related) 4. Renal: serum creatinine (SCr) within normal range for age (see table 2.3). If SCr is outside normal range for age, creatinine clearance (CrCl) \> 40 mL/min/1.73m2 must be obtained (measured by 24-hour (hr) urine specimen or nuclear glomerular filtration rate (GFR), or calculated GFR (by Cockcroft-Gault formula for those aged ≥ 18 years; by Original Schwartz estimate for those \< 18 years)) 7. Subjects ≥ 18 years of age must have the ability to give informed consent according to applicable regulatory and local institutional requirements. Legal guardian permission must be obtained for subjects \< 18 years of age. Pediatric subjects will be included in age appropriate discussion in order to obtain assent. 8. Subjects with documentation of confirmed HIV-1 infection (i.e. HIV-positive), and a hematologic malignancy who meets all other eligibility requirements must: 1. Receive only RIC regimen (i.e. Regimen A) 2. Be willing to comply with effective antiretroviral therapy (ARV) 3. Have achieved a sustained virologic response for 12 weeks after cessation of hepatitis C antiviral treatment (in HIV-positive subjects with hepatitis C)
Exclusion criteria
1. HLA-matched related or 8/8 allele matched (HLA-A, -B, -C, -DRB1) unrelated donor available. This exclusion does not apply to HIV-positive subjects who have a CCR5delta32 homozygous donor. 2. Autologous HCT \< 3 months prior to the time of signing the informed consent form 3. Females who are breast-feeding or pregnant 4. HIV-positive subjects: 1. Acquired immunodeficiency syndrome (AIDS) related syndromes or symptoms that may pose an excessive risk for transplantation-related morbidity as determined by the Treatment Review Committee (see Appendix D). 2. Untreatable HIV infection due to multidrug ARV resistance. Subjects with a detectable or standard viral load \> 750 copies/mL should be evaluated with an HIV drug resistance test (HIV-1 genotype). The results should be included as part of the ARV review (described in Appendix D). 3. May not be currently prescribed ritonavir, cobacistat and/or zidovudine 5. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings) 6. Prior allogeneic HCT 7. History of primary idiopathic myelofibrosis 8. MDS subjects may not receive RIC and must be \< 50 years of age at the time of signing the informed consent form
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 365 days post transplant | Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 180 days and 365 days post-transplant | Time from HCT until the documentation of disease progression / relapse or death due to any cause, whichever occurs first. Progression-free survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator. |
| Cumulative Incidence of Neutrophil Recovery | 100 days and 365 days post transplant | Achieving a donor derived ANC ≥ 500/mm3 for 3 consecutive laboratory values on different days. A cumulative incidence will be computed along with a 90% CI. |
| Cumulative Incidence of Platelet Recovery | 100 days and 365 days post transplant | Achieving a platelet count ≥ 20,000/μL for 3 consecutive laboratory values on different days (with no platelet transfusions in the preceding seven days). A cumulative incidence will be computed along with a 90% CI. |
| Cumulative Incidence of Acute GVHD | 100 days post-transplant | Any skin, gastrointestinal or liver abnormalities fulfilling the BMT CTN Manual of Operations (2013) criteria of grades II-IV acute GVHD. A cumulative incidence will be computed along with a 90% CI. Any skin, gastrointestinal or liver abnormalities fulfilling the BMT CTN Manual of Operations (2013) criteria of grades III-IV acute GVHD. A cumulative incidence will be computed along with a 90% CI. |
| Grades II-IV Acute GVHD | 100 days | Any skin, gastrointestinal or liver abnormalities fulfilling the BMT CTN Manual of Operations (2013) criteria of grades II-IV acute GVHD. A cumulative incidence will be computed along with a 90% CI. |
| Grades III-IV Acute GVHD | 100 days | Any skin, gastrointestinal or liver abnormalities fulfilling the BMT CTN Manual of Operations (2013) criteria of grades III-IV acute GVHD. A cumulative incidence will be computed along with a 90% CI. |
| Cumulative Incidence of Chronic GVHD | 180 days and 365 days post-transplant | Per National Institutes of Health (NIH) Consensus Criteria and includes organ involvement and severity, and overall global composite score (mild/moderate/severe). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator. |
| Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 CMV Reactivation or Infection | 100 days, 180 days, and 365 days | Grade 2: Clinically active CMV infection (e.g. symptoms, cytopenias) or CMV Viremia not decreasing by at least 2/3 of the baseline value after 2 weeks of therapy; Grade 3: CMV end-organ involvement (pneumonitis, enteritis, retinitis). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator. |
| Cumulative Incidences of Viral Reactivations and Infections: Grade 3 CMV Infection | 100 days, 180 days, and 365 days | CMV end-organ involvement (pneumonitis, enteritis, retinitis) ). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator. |
| Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 EBV Infection | 100 days, 180 days, and 365 days | Grade 2: EBV reactivation requiring institution of therapy with rituximab; Grade 3: EBV post-transplant lymphoproliferative disorder). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator. |
| Cumulative Incidences of Viral Reactivations and Infections: Grade 2 BK Virus Infection | 100 days, 180 days, 365 days | BK viremia or viruria with clinical consequence requiring prolonged therapy and/or surgical intervention). A cumulative incidence will be computed along with a 90% CI. |
| Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 Adenovirus Infection | 100 days, 180 days, and 365 days | Grade 2: Adenoviral URI, viremia, or symptomatic viruria requiring treatment; Grade 3: ADV with end-organ involvement (except conjunctivitis and upper respiratory tract) ). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator. |
| Cumulative Incidences of Viral Reactivations and Infections: Grade 2 HHV-6 Infection | 100 days, 180 days, 365 days | Clinically active HHV-6 infection (e.g. symptoms, cytopenias) or HHV-6 viremia without viral load decline 0.5 log after 2 weeks of therapy). A cumulative incidence will be computed along with a 90% CI. |
| Cumulative Incidence of Relapse/Progression | 180 days and 365 days post-transplant | Defined by either morphological, cytogenetic/molecular or radiological evidence of disease consistent with pre-HCT features. A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator. |
| Cumulative Incidences of Thrombotic Microangiopathy (TMA) and Hepatic Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) | 365 days post transplant | TMA is defined as (Ho et al., 2005): 1. RBC fragmentation and \>2 schistocytes per high-power field on peripheral smear 2. Concurrent increased serum LDH above institutional baseline 3. Concurrent renal and/or neurologic dysfunction without other explanation 4. Negative direct and indirect Coombs test results A cumulative incidence will be computed along with a 90% CI. VOD/SOS is defined as: In the first 20 days after HCT, the presence of ≥2 of the following: 1. Bilirubin \>2 mg/Dl, 2. Hepatomegaly or pain in right upper quadrant, 3. Weight gain (\>2% basal weight). A cumulative incidence will be computed along with a 90% CI. |
| Transplant-related Mortality | 100 days, 180 days, and 365 days post-transplant | Death without evidence of disease progression or recurrence. A cumulative incidence will be computed along with a 90% CI. |
| Donor Chimerism | 28 days, 56 days, 100 days, 180 days, and 365 days post-transplant | Peripheral blood chimerism (% of donor chimerism) in whole blood (unsorted). The degree of donor chimerism will be summarized using descriptive statistics. |
| Peripheral Blood Chimerism | 56 days post-transplant | The frequency of subjects with Peripheral blood (unsorted) chimerism\>95% at 56 days will be described. |
| Proportion of Subjects Proceeding to Transplant | Pre-HCT | The proportion of subjects proceeding to HCT after informed consent. |
| Time From Search to Donor Identification | Pre-HCT | Time from search to donor identification Time from preliminary search to formal donor activation. |
| Donor Selection Characteristics: HLA Match | Pre-HCT | Number of matched donor and recipient HLA allele pairs. A matched donor would have 8/8 HLA allele pairs matching; mismatched donors listed below have one to four mismatched HLA allele pairs at HLA-A, -B, -C, or -DRB1. |
| Donor Selection Characteristics: Donor Age | Pre-HCT | Donor age |
| Donor Selection Characteristics: Donor Age, Categorical | Pre-HCT | Donor age, categorical |
| Donor Selection Characteristics: Donor Weight | Pre-HCT | Donor weight |
| Donor Selection Characteristics: Donor Sex | Pre-HCT | Donor sex |
| Donor Selection Characteristics: Donor and Recipient Sex | Pre-HCT | Donor-recipient sex match |
| Donor Selection Characteristics: Donor and Recipient CMV Serostatus | Pre-HCT | Donor-recipient Cytomegalovirus (CMV) serostatus match |
| Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Pre-HCT | Donor-recipient ABO group match |
| Donor Clonal Hematopoiesis | 100 days and 365 days post-transplant | The proportion of subjects developing donor clonal hematopoiesis |
| Subgroup Analysis of HIV-positive Subjects | 365 days post transplant | If CCR5delta32 homozygous donors are successfully found and used for one or more HIV-positive subjects, a descriptive analysis of baseline characteristics and outcomes for those HIV-positive subjects will be conducted, including the viral load detected over time obtained from collected samples. |
| Cumulative Incidence of Primary Graft Failure | 56 days post-transplant | Lack of donor-derived neutrophil engraftment. The frequency of subjects experiencing primary graft failure by 56 days will be described. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Myeloablative Conditioning (MAC) Participants received one of three regimens: cyclophosphamide and total body irradiation; busulfan and cyclophosphamide; or fludarabine and busulfan | 40 |
| Reduced Intensity Conditioning (RIC) Participants received one of two regimens: fludarabine, cyclophosphamide, and low-dose total body irradiation | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 10 | 8 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Myeloablative Conditioning (MAC) | Reduced Intensity Conditioning (RIC) |
|---|---|---|---|
| Age, Continuous | 51.5 years | 48.5 years | 59.5 years |
| CMV serostatus Negative | 34 Participants | 16 Participants | 18 Participants |
| CMV serostatus Positive | 46 Participants | 24 Participants | 22 Participants |
| Conditioning Regimen Bu and Cy | 3 Participants | 3 Participants | 0 Participants |
| Conditioning Regimen Bu and Flu | 31 Participants | 31 Participants | 0 Participants |
| Conditioning Regimen TBI and Cy | 6 Participants | 6 Participants | 0 Participants |
| Conditioning Regimen TBI, CY, and Flu | 40 Participants | 0 Participants | 40 Participants |
| Disease and disease status at HCT ALL (CR1) | 13 Participants | 7 Participants | 6 Participants |
| Disease and disease status at HCT ALL (CR2+) | 4 Participants | 3 Participants | 1 Participants |
| Disease and disease status at HCT AML (CR1) | 32 Participants | 22 Participants | 10 Participants |
| Disease and disease status at HCT AML (CR2+) | 3 Participants | 1 Participants | 2 Participants |
| Disease and disease status at HCT AML (PIF) | 2 Participants | 0 Participants | 2 Participants |
| Disease and disease status at HCT CLL (CR) | 3 Participants | 0 Participants | 3 Participants |
| Disease and disease status at HCT HL (CR1) | 2 Participants | 0 Participants | 2 Participants |
| Disease and disease status at HCT HL (PIF) | 2 Participants | 0 Participants | 2 Participants |
| Disease and disease status at HCT HL (Relapse) | 1 Participants | 0 Participants | 1 Participants |
| Disease and disease status at HCT MDS (CR) | 1 Participants | 1 Participants | 0 Participants |
| Disease and disease status at HCT MDS (HI) | 1 Participants | 1 Participants | 0 Participants |
| Disease and disease status at HCT NHL (CR1) | 5 Participants | 0 Participants | 5 Participants |
| Disease and disease status at HCT NHL (CR2+) | 4 Participants | 1 Participants | 3 Participants |
| Disease and disease status at HCT NHL (PIF) | 1 Participants | 0 Participants | 1 Participants |
| Disease and disease status at HCT NHL (Relapse) | 2 Participants | 0 Participants | 2 Participants |
| Disease and disease status at HCT Other acute leukemia (CR1) | 3 Participants | 3 Participants | 0 Participants |
| Disease and disease status at HCT Other acute leukemia (CR2+) | 1 Participants | 1 Participants | 0 Participants |
| Disease status pre-HCT CR | 4 Participants | 1 Participants | 3 Participants |
| Disease status pre-HCT CR1 | 55 Participants | 32 Participants | 23 Participants |
| Disease status pre-HCT CR2+ | 12 Participants | 6 Participants | 6 Participants |
| Disease status pre-HCT HI | 1 Participants | 1 Participants | 0 Participants |
| Disease status pre-HCT PIF | 5 Participants | 0 Participants | 5 Participants |
| Disease status pre-HCT Progression/Relapse | 3 Participants | 0 Participants | 3 Participants |
| Donor age 18-29 years of age | 47 Participants | 24 Participants | 23 Participants |
| Donor age 30-39 years of age | 20 Participants | 9 Participants | 11 Participants |
| Donor age 40-49 years of age | 10 Participants | 4 Participants | 6 Participants |
| Donor age 50-59 years of age | 3 Participants | 3 Participants | 0 Participants |
| Donor/recipient ABO match Bi-directional | 3 Participants | 0 Participants | 3 Participants |
| Donor/recipient ABO match Major mismatch | 16 Participants | 8 Participants | 8 Participants |
| Donor/recipient ABO match Matched | 44 Participants | 20 Participants | 24 Participants |
| Donor/recipient ABO match Minor mismatch | 17 Participants | 12 Participants | 5 Participants |
| Donor/recipient CMV serostatus -/- | 19 Participants | 7 Participants | 12 Participants |
| Donor/recipient CMV serostatus -/+ | 19 Participants | 9 Participants | 10 Participants |
| Donor/recipient CMV serostatus +/- | 11 Participants | 6 Participants | 5 Participants |
| Donor/recipient CMV serostatus +/+ | 31 Participants | 18 Participants | 13 Participants |
| Donor/recipient sex F-F | 18 Participants | 9 Participants | 9 Participants |
| Donor/recipient sex F-M | 18 Participants | 11 Participants | 7 Participants |
| Donor/recipient sex M-F | 20 Participants | 8 Participants | 12 Participants |
| Donor/recipient sex M-M | 24 Participants | 12 Participants | 12 Participants |
| Donor Sex Female | 36 Participants | 20 Participants | 16 Participants |
| Donor Sex Male | 44 Participants | 20 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 12 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 28 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HCT Comorbidity Index score 0 | 13 Participants | 4 Participants | 9 Participants |
| HCT Comorbidity Index score 1 | 10 Participants | 2 Participants | 8 Participants |
| HCT Comorbidity Index score 2 | 14 Participants | 10 Participants | 4 Participants |
| HCT Comorbidity Index score 3+ | 43 Participants | 24 Participants | 19 Participants |
| HIV infection pre-HCT No | 76 Participants | 40 Participants | 36 Participants |
| HIV infection pre-HCT Yes | 4 Participants | 0 Participants | 4 Participants |
| HLA match, categorical 4/8 | 5 Participants | 1 Participants | 4 Participants |
| HLA match, categorical 5/8 | 7 Participants | 5 Participants | 2 Participants |
| HLA match, categorical 6/8 | 19 Participants | 8 Participants | 11 Participants |
| HLA match, categorical 7/8 | 49 Participants | 26 Participants | 23 Participants |
| Infused CD34 cells, x10^6/kg | 2.66 cells x10^6/kg | 2.72 cells x10^6/kg | 2.2 cells x10^6/kg |
| Infused total nucleated cells x10^8/kg | 2.8 cells x10^8/kg | 2.81 cells x10^8/kg | 2.8 cells x10^8/kg |
| Karnofsky/Lansky performance score 100 | 15 Participants | 5 Participants | 10 Participants |
| Karnofsky/Lansky performance score 70 | 3 Participants | 2 Participants | 1 Participants |
| Karnofsky/Lansky performance score 80 | 24 Participants | 12 Participants | 12 Participants |
| Karnofsky/Lansky performance score 90 | 38 Participants | 21 Participants | 17 Participants |
| Number of prior autoHCTs 0 | 75 Participants | 38 Participants | 37 Participants |
| Number of prior autoHCTs 1 | 5 Participants | 2 Participants | 3 Participants |
| Primary Disease Acute leukemia | 60 Participants | 37 Participants | 23 Participants |
| Primary Disease CLL | 3 Participants | 0 Participants | 3 Participants |
| Primary Disease Lymphoma | 15 Participants | 1 Participants | 14 Participants |
| Primary Disease MDS | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 9 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 60 Participants | 29 Participants | 31 Participants |
| Refined disease risk index High | 10 Participants | 3 Participants | 7 Participants |
| Refined disease risk index Intermediate | 50 Participants | 29 Participants | 21 Participants |
| Refined disease risk index Low | 9 Participants | 3 Participants | 6 Participants |
| Refined disease risk index N/A | 8 Participants | 5 Participants | 3 Participants |
| Refined disease risk index Very high | 3 Participants | 0 Participants | 3 Participants |
| Region of Enrollment United States | 80 Participants | 40 Participants | 40 Participants |
| Sex: Female, Male Female | 38 Participants | 17 Participants | 21 Participants |
| Sex: Female, Male Male | 42 Participants | 23 Participants | 19 Participants |
| Time between diagnosis to HCT < 6 months | 24 Participants | 14 Participants | 10 Participants |
| Time between diagnosis to HCT ≥ 6 months | 56 Participants | 26 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 40 | 8 / 40 |
| other Total, other adverse events | 5 / 40 | 0 / 40 |
| serious Total, serious adverse events | 12 / 40 | 13 / 40 |
Outcome results
Primary
Overall Survival
Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator.
Time frame: 365 days post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Overall Survival | 72.3 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Overall Survival | 78.9 percentage of participants |
Secondary
Cumulative Incidence of Acute GVHD
Any skin, gastrointestinal or liver abnormalities fulfilling the BMT CTN Manual of Operations (2013) criteria of grades II-IV acute GVHD. A cumulative incidence will be computed along with a 90% CI. Any skin, gastrointestinal or liver abnormalities fulfilling the BMT CTN Manual of Operations (2013) criteria of grades III-IV acute GVHD. A cumulative incidence will be computed along with a 90% CI.
Time frame: 100 days post-transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Acute GVHD | Grades II-IV acute GVHD | 42.5 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Acute GVHD | Grades III-IV acute GVHD | 17.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Acute GVHD | Grades II-IV acute GVHD | 32.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Acute GVHD | Grades III-IV acute GVHD | 0 percentage of participants |
Secondary
Cumulative Incidence of Chronic GVHD
Per National Institutes of Health (NIH) Consensus Criteria and includes organ involvement and severity, and overall global composite score (mild/moderate/severe). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator.
Time frame: 180 days and 365 days post-transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Chronic GVHD | 180 days | 27.6 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Chronic GVHD | 365 days | 35.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Chronic GVHD | 180 days | 10 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Chronic GVHD | 365 days | 17.5 percentage of participants |
Secondary
Cumulative Incidence of Neutrophil Recovery
Achieving a donor derived ANC ≥ 500/mm3 for 3 consecutive laboratory values on different days. A cumulative incidence will be computed along with a 90% CI.
Time frame: 100 days and 365 days post transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Neutrophil Recovery | 100 days | 97.5 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Neutrophil Recovery | 365 days | 97.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Neutrophil Recovery | 100 days | 97.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Neutrophil Recovery | 365 days | 97.5 percentage of participants |
Secondary
Cumulative Incidence of Platelet Recovery
Achieving a platelet count ≥ 20,000/μL for 3 consecutive laboratory values on different days (with no platelet transfusions in the preceding seven days). A cumulative incidence will be computed along with a 90% CI.
Time frame: 100 days and 365 days post transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Platelet Recovery | 100 days | 87.5 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Platelet Recovery | 365 days | 90 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Platelet Recovery | 100 days | 95 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Platelet Recovery | 365 days | 95 percentage of participants |
Secondary
Cumulative Incidence of Primary Graft Failure
Lack of donor-derived neutrophil engraftment. The frequency of subjects experiencing primary graft failure by 56 days will be described.
Time frame: 56 days post-transplant
Population: Primary graft failure Lack of donor-derived neutrophil engraftment. The frequency of subjects experiencing primary graft failure by 56 days will be described. Transplanted participants surviving a minimum of 14 days post HCT and have complete data for both event status and event date.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Primary Graft Failure | 0 Participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Primary Graft Failure | 3 Participants |
Secondary
Cumulative Incidence of Relapse/Progression
Defined by either morphological, cytogenetic/molecular or radiological evidence of disease consistent with pre-HCT features. A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator.
Time frame: 180 days and 365 days post-transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Relapse/Progression | 180 days | 22.6 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidence of Relapse/Progression | 365 days | 30.4 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Relapse/Progression | 365 days | 22.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidence of Relapse/Progression | 180 days | 20 percentage of participants |
Secondary
Cumulative Incidences of Thrombotic Microangiopathy (TMA) and Hepatic Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS)
TMA is defined as (Ho et al., 2005): 1. RBC fragmentation and \>2 schistocytes per high-power field on peripheral smear 2. Concurrent increased serum LDH above institutional baseline 3. Concurrent renal and/or neurologic dysfunction without other explanation 4. Negative direct and indirect Coombs test results A cumulative incidence will be computed along with a 90% CI. VOD/SOS is defined as: In the first 20 days after HCT, the presence of ≥2 of the following: 1. Bilirubin \>2 mg/Dl, 2. Hepatomegaly or pain in right upper quadrant, 3. Weight gain (\>2% basal weight). A cumulative incidence will be computed along with a 90% CI.
Time frame: 365 days post transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Thrombotic Microangiopathy (TMA) and Hepatic Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) | Thrombotic microangiopathy (TMA) | 5 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Thrombotic Microangiopathy (TMA) and Hepatic Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) | Hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) | 10 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Thrombotic Microangiopathy (TMA) and Hepatic Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) | Thrombotic microangiopathy (TMA) | 0 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Thrombotic Microangiopathy (TMA) and Hepatic Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) | Hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) | 2.5 percentage of participants |
Secondary
Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 Adenovirus Infection
Grade 2: Adenoviral URI, viremia, or symptomatic viruria requiring treatment; Grade 3: ADV with end-organ involvement (except conjunctivitis and upper respiratory tract) ). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator.
Time frame: 100 days, 180 days, and 365 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 Adenovirus Infection | 100 days | 2.6 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 Adenovirus Infection | 180 days | 9 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 Adenovirus Infection | 365 days | 9 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 Adenovirus Infection | 100 days | 0 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 Adenovirus Infection | 180 days | 9.4 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 Adenovirus Infection | 365 days | 12.6 percentage of participants |
Secondary
Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 CMV Reactivation or Infection
Grade 2: Clinically active CMV infection (e.g. symptoms, cytopenias) or CMV Viremia not decreasing by at least 2/3 of the baseline value after 2 weeks of therapy; Grade 3: CMV end-organ involvement (pneumonitis, enteritis, retinitis). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator.
Time frame: 100 days, 180 days, and 365 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 CMV Reactivation or Infection | 100 days | 10.4 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 CMV Reactivation or Infection | 180 days | 10.4 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 CMV Reactivation or Infection | 365 days | 10.4 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 CMV Reactivation or Infection | 100 days | 7.6 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 CMV Reactivation or Infection | 180 days | 7.6 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 CMV Reactivation or Infection | 365 days | 7.6 percentage of participants |
Secondary
Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 EBV Infection
Grade 2: EBV reactivation requiring institution of therapy with rituximab; Grade 3: EBV post-transplant lymphoproliferative disorder). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator.
Time frame: 100 days, 180 days, and 365 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 EBV Infection | 100 days | 0 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 EBV Infection | 180 days | 2.9 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 EBV Infection | 365 days | 2.9 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 EBV Infection | 100 days | 0 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 EBV Infection | 180 days | 0 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 EBV Infection | 365 days | 0 percentage of participants |
Secondary
Cumulative Incidences of Viral Reactivations and Infections: Grade 2 BK Virus Infection
BK viremia or viruria with clinical consequence requiring prolonged therapy and/or surgical intervention). A cumulative incidence will be computed along with a 90% CI.
Time frame: 100 days, 180 days, 365 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 BK Virus Infection | 100 days | 26.7 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 BK Virus Infection | 180 days | 26.7 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 BK Virus Infection | 365 days | 26.7 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 BK Virus Infection | 100 days | 29.7 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 BK Virus Infection | 180 days | 29.7 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 BK Virus Infection | 365 days | 29.7 percentage of participants |
Secondary
Cumulative Incidences of Viral Reactivations and Infections: Grade 2 HHV-6 Infection
Clinically active HHV-6 infection (e.g. symptoms, cytopenias) or HHV-6 viremia without viral load decline 0.5 log after 2 weeks of therapy). A cumulative incidence will be computed along with a 90% CI.
Time frame: 100 days, 180 days, 365 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 HHV-6 Infection | 100 days | 12.5 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 HHV-6 Infection | 180 days | 12.5 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 HHV-6 Infection | 365 days | 12.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 HHV-6 Infection | 100 days | 5.1 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 HHV-6 Infection | 180 days | 5.1 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 2 HHV-6 Infection | 365 days | 5.1 percentage of participants |
Secondary
Cumulative Incidences of Viral Reactivations and Infections: Grade 3 CMV Infection
CMV end-organ involvement (pneumonitis, enteritis, retinitis) ). A cumulative incidence will be computed along with a 90% CI. Death from any cause. The time to this event is the time from HCT to death, loss to follow-up, or end of study (whichever comes first). The overall survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator.
Time frame: 100 days, 180 days, and 365 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 3 CMV Infection | 100 days | 0 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 3 CMV Infection | 180 days | 0 percentage of participants |
| Myeloablative Conditioning (MAC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 3 CMV Infection | 365 days | 0 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 3 CMV Infection | 100 days | 2.6 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 3 CMV Infection | 180 days | 2.6 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Cumulative Incidences of Viral Reactivations and Infections: Grade 3 CMV Infection | 365 days | 2.6 percentage of participants |
Secondary
Donor Chimerism
Peripheral blood chimerism (% of donor chimerism) in whole blood (unsorted). The degree of donor chimerism will be summarized using descriptive statistics.
Time frame: 28 days, 56 days, 100 days, 180 days, and 365 days post-transplant
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Chimerism | 56 days | 100 percentage of donor chimerism |
| Myeloablative Conditioning (MAC) | Donor Chimerism | 180 days | 100 percentage of donor chimerism |
| Myeloablative Conditioning (MAC) | Donor Chimerism | 100 days | 100 percentage of donor chimerism |
| Myeloablative Conditioning (MAC) | Donor Chimerism | 365 days | 100 percentage of donor chimerism |
| Myeloablative Conditioning (MAC) | Donor Chimerism | 28 days | 100 percentage of donor chimerism |
| Reduced Intensity Conditioning (RIC) | Donor Chimerism | 365 days | 100 percentage of donor chimerism |
| Reduced Intensity Conditioning (RIC) | Donor Chimerism | 28 days | 99.1 percentage of donor chimerism |
| Reduced Intensity Conditioning (RIC) | Donor Chimerism | 56 days | 100 percentage of donor chimerism |
| Reduced Intensity Conditioning (RIC) | Donor Chimerism | 100 days | 100 percentage of donor chimerism |
| Reduced Intensity Conditioning (RIC) | Donor Chimerism | 180 days | 100 percentage of donor chimerism |
Secondary
Donor Clonal Hematopoiesis
The proportion of subjects developing donor clonal hematopoiesis
Time frame: 100 days and 365 days post-transplant
Population: All participants assessed for donor clonal hematopoiesis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Clonal Hematopoiesis | 0 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Clonal Hematopoiesis | 0 Participants |
Secondary
Donor Selection Characteristics: Donor Age
Donor age
Time frame: Pre-HCT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor Age | 27 years |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor Age | 29 years |
| Total | Donor Selection Characteristics: Donor Age | 29 years |
Secondary
Donor Selection Characteristics: Donor Age, Categorical
Donor age, categorical
Time frame: Pre-HCT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor Age, Categorical | 18-29 | 24 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor Age, Categorical | 30-39 | 9 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor Age, Categorical | 40-49 | 4 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor Age, Categorical | 50-59 | 3 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor Age, Categorical | 50-59 | 0 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor Age, Categorical | 18-29 | 23 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor Age, Categorical | 40-49 | 6 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor Age, Categorical | 30-39 | 11 Participants |
| Total | Donor Selection Characteristics: Donor Age, Categorical | 50-59 | 3 Participants |
| Total | Donor Selection Characteristics: Donor Age, Categorical | 30-39 | 20 Participants |
| Total | Donor Selection Characteristics: Donor Age, Categorical | 40-49 | 10 Participants |
| Total | Donor Selection Characteristics: Donor Age, Categorical | 18-29 | 47 Participants |
Secondary
Donor Selection Characteristics: Donor and Recipient ABO Blood Match
Donor-recipient ABO group match
Time frame: Pre-HCT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Major mismatch | 8 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Matched | 20 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Bidirectional | 0 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Minor mismatch | 12 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Major mismatch | 8 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Minor mismatch | 5 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Bidirectional | 3 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Matched | 24 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Bidirectional | 3 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Matched | 44 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Minor mismatch | 17 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient ABO Blood Match | Major mismatch | 16 Participants |
Secondary
Donor Selection Characteristics: Donor and Recipient CMV Serostatus
Donor-recipient Cytomegalovirus (CMV) serostatus match
Time frame: Pre-HCT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | +/+ | 18 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | +/- | 6 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | -/+ | 9 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | -/- | 7 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | -/- | 12 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | +/+ | 13 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | -/+ | 10 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | +/- | 5 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | -/- | 19 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | +/- | 11 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | -/+ | 19 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient CMV Serostatus | +/+ | 31 Participants |
Secondary
Donor Selection Characteristics: Donor and Recipient Sex
Donor-recipient sex match
Time frame: Pre-HCT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient Sex | Male and male | 12 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient Sex | Male and female | 8 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient Sex | Female and male | 11 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor and Recipient Sex | Female and female | 9 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient Sex | Female and female | 9 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient Sex | Male and male | 12 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient Sex | Female and male | 7 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor and Recipient Sex | Male and female | 12 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient Sex | Female and female | 18 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient Sex | Male and female | 20 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient Sex | Female and male | 18 Participants |
| Total | Donor Selection Characteristics: Donor and Recipient Sex | Male and male | 24 Participants |
Secondary
Donor Selection Characteristics: Donor Sex
Donor sex
Time frame: Pre-HCT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor Sex | Male | 20 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor Sex | Female | 20 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor Sex | Male | 24 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor Sex | Female | 16 Participants |
| Total | Donor Selection Characteristics: Donor Sex | Male | 44 Participants |
| Total | Donor Selection Characteristics: Donor Sex | Female | 36 Participants |
Secondary
Donor Selection Characteristics: Donor Weight
Donor weight
Time frame: Pre-HCT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: Donor Weight | 77 kg |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: Donor Weight | 77 kg |
| Total | Donor Selection Characteristics: Donor Weight | 77 kg |
Secondary
Donor Selection Characteristics: HLA Match
Number of matched donor and recipient HLA allele pairs. A matched donor would have 8/8 HLA allele pairs matching; mismatched donors listed below have one to four mismatched HLA allele pairs at HLA-A, -B, -C, or -DRB1.
Time frame: Pre-HCT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: HLA Match | 7 out of 8 matching HLA allele pairs | 26 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: HLA Match | 6 out of 8 matching HLA allele pairs | 8 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: HLA Match | 5 out of 8 matching HLA allele pairs | 5 Participants |
| Myeloablative Conditioning (MAC) | Donor Selection Characteristics: HLA Match | 4 out of 8 matching HLA allele pairs | 1 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: HLA Match | 4 out of 8 matching HLA allele pairs | 4 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: HLA Match | 7 out of 8 matching HLA allele pairs | 23 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: HLA Match | 5 out of 8 matching HLA allele pairs | 2 Participants |
| Reduced Intensity Conditioning (RIC) | Donor Selection Characteristics: HLA Match | 6 out of 8 matching HLA allele pairs | 11 Participants |
| Total | Donor Selection Characteristics: HLA Match | 4 out of 8 matching HLA allele pairs | 5 Participants |
| Total | Donor Selection Characteristics: HLA Match | 6 out of 8 matching HLA allele pairs | 19 Participants |
| Total | Donor Selection Characteristics: HLA Match | 5 out of 8 matching HLA allele pairs | 7 Participants |
| Total | Donor Selection Characteristics: HLA Match | 7 out of 8 matching HLA allele pairs | 49 Participants |
Secondary
Grades III-IV Acute GVHD
Any skin, gastrointestinal or liver abnormalities fulfilling the BMT CTN Manual of Operations (2013) criteria of grades III-IV acute GVHD. A cumulative incidence will be computed along with a 90% CI.
Time frame: 100 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Grades III-IV Acute GVHD | 17.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Grades III-IV Acute GVHD | 0 percentage of participants |
Secondary
Grades II-IV Acute GVHD
Any skin, gastrointestinal or liver abnormalities fulfilling the BMT CTN Manual of Operations (2013) criteria of grades II-IV acute GVHD. A cumulative incidence will be computed along with a 90% CI.
Time frame: 100 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Grades II-IV Acute GVHD | 42.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Grades II-IV Acute GVHD | 32.5 percentage of participants |
Secondary
Peripheral Blood Chimerism
The frequency of subjects with Peripheral blood (unsorted) chimerism\>95% at 56 days will be described.
Time frame: 56 days post-transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Peripheral Blood Chimerism | 24 Participants |
| Reduced Intensity Conditioning (RIC) | Peripheral Blood Chimerism | 27 Participants |
Secondary
Progression-free Survival
Time from HCT until the documentation of disease progression / relapse or death due to any cause, whichever occurs first. Progression-free survival probability and 90% CI will be calculated by the Kaplan Meier product limit estimator.
Time frame: 180 days and 365 days post-transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Progression-free Survival | 180 days | 69.9 percentage of participants |
| Myeloablative Conditioning (MAC) | Progression-free Survival | 365 days | 62.1 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Progression-free Survival | 180 days | 72.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Progression-free Survival | 365 days | 67.5 percentage of participants |
Secondary
Proportion of Subjects Proceeding to Transplant
The proportion of subjects proceeding to HCT after informed consent.
Time frame: Pre-HCT
Population: Participants who signed informed consent.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Proportion of Subjects Proceeding to Transplant | 80 Participants |
Secondary
Subgroup Analysis of HIV-positive Subjects
If CCR5delta32 homozygous donors are successfully found and used for one or more HIV-positive subjects, a descriptive analysis of baseline characteristics and outcomes for those HIV-positive subjects will be conducted, including the viral load detected over time obtained from collected samples.
Time frame: 365 days post transplant
Population: Four subjects with HIV-positive, no statistical analysis for this outcome measure was completed due to limited HIV-positive rate. Descriptive analysis provided.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Subgroup Analysis of HIV-positive Subjects | Survival Status: Alive | 0 Participants |
| Myeloablative Conditioning (MAC) | Subgroup Analysis of HIV-positive Subjects | Survival Status: Deceased (relapse) | 0 Participants |
| Myeloablative Conditioning (MAC) | Subgroup Analysis of HIV-positive Subjects | Survival Status: Deceased (fungal infection) | 0 Participants |
| Reduced Intensity Conditioning (RIC) | Subgroup Analysis of HIV-positive Subjects | Survival Status: Alive | 1 Participants |
| Reduced Intensity Conditioning (RIC) | Subgroup Analysis of HIV-positive Subjects | Survival Status: Deceased (relapse) | 2 Participants |
| Reduced Intensity Conditioning (RIC) | Subgroup Analysis of HIV-positive Subjects | Survival Status: Deceased (fungal infection) | 1 Participants |
Secondary
Time From Search to Donor Identification
Time from search to donor identification Time from preliminary search to formal donor activation.
Time frame: Pre-HCT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Myeloablative Conditioning (MAC) | Time From Search to Donor Identification | 77.5 days |
| Reduced Intensity Conditioning (RIC) | Time From Search to Donor Identification | 88.5 days |
Secondary
Transplant-related Mortality
Death without evidence of disease progression or recurrence. A cumulative incidence will be computed along with a 90% CI.
Time frame: 100 days, 180 days, and 365 days post-transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Myeloablative Conditioning (MAC) | Transplant-related Mortality | 100 days | 5 percentage of participants |
| Myeloablative Conditioning (MAC) | Transplant-related Mortality | 180 days | 7.5 percentage of participants |
| Myeloablative Conditioning (MAC) | Transplant-related Mortality | 365 days | 7.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Transplant-related Mortality | 100 days | 7.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Transplant-related Mortality | 180 days | 7.5 percentage of participants |
| Reduced Intensity Conditioning (RIC) | Transplant-related Mortality | 365 days | 10 percentage of participants |