Myeloablative Haploidentical BMT With Post-transplant Cyc... | NCT02120157

NCT02120157

ID	Type	Description	Link
NA_00091665	Other Identifier	JHM IRB

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Haploidentical BMT with PTCy for acute leukemias and MDS	Experimental	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus	Drug: Cyclophosphamide Radiation: TBI Drug: Busulfan Other: Unmanipulated Bone Marrow Drug: Tacrolimus Drug: Mycophenolate mofetil

Name	Type	Description	Arm Group Labels	Other Names
Cyclophosphamide	Drug	Chemotherapy administration	Haploidentical BMT with PTCy for acute leukemias and MDS

Measure	Description	Time Frame
Cumulative Incidence of Non-relapse Mortality	Cumulative incidence (measured as a percentage) of non-relapse mortality at 180 days following myeloablative, Human Leukocyte Antigen (HLA)-mismatched bone marrow transplant (BMT) for patients with high risk hematologic malignancies.	Day 180

Measure	Description	Time Frame
Number of Participants With Donor Cell Engraftment	Number of Participants with Donor Cell Engraftment at Day 60 following myeloablative, HLA-mismatched BMT.	Day 60
Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patient age 0.5-25years
Patients must have a first-degree related donor or half-sibling who is at minimum HLA haploidentical. The donor and recipient must be identical at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.
An unrelated donor search is not required for a patient to be eligible for this protocol, or a donor search and donor mobilization may be abandoned if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6-8 weeks from referral to transplant or a low-likelihood of finding a matched, unrelated donor. Patients with an eligible HLA-matched RELATED should not be enrolled on this trial.
Patients must have at least one of the following high-risk conditions listed below:
Acute lymphocytic leukemia (ALL) in CR1* as defined by at least one of the following:

hypodiploidy, induction failure,Minimal residual disease (MRD) after consolidation

- Acute myeloid leukemia (AML) in CR1 with high risk features defined as: High allelic ratio FLT3/ITD+, Monosomy 7, Del (5q), Standard risk cytogenetics with positive minimal residual disease at the end of Induction I chemotherapy (for patients being treated on or according to Children's Oncology Group (COG) AAML1031 study who have had MRD studies sent to Seattle or performed at their local institution where the flow assay is sensitive enough to detect > 0.1% blasts)

Acute Leukemia in 2nd or subsequent CR (CR>2)
Mixed phenotype/Undifferentiated Leukemia in 1st or subsequent CR*
Secondary or therapy related leukemia in CR > 1
Natural Killer (NK) cell lymphoblastic leukemia CR > 1
Myelodysplastic syndrome (MDS)
Juvenile myelomonocytic leukemia (JMML) (patients are eligible if they are not eligible for COG1221 study)
Prior transplant eligible if < 18yo, >6 months has elapsed since BMT, and patient is off immunosuppression for > 3 months with no Graft versus host disease (GVHD)
No known active Central nervous system (CNS) involvement or extramedullary involvement by malignancy. Such disease treated into remission is permitted.
Acute Leukemia - Remission is defined as morphology with < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > 20% cellularity.

Exclusion Criteria:

Poor cardiac function: left ventricular ejection fraction <45% as determined by Multigated acquisition scan (MUGA) or Echocardiogram (ECHO). For pediatric patients Left ventricular ejection fraction (LVEF) <45% or a shortening fraction below normal limits for age.
Symptomatic pulmonary disease. Poor pulmonary function: Forced expiratory volume (FEV1), Forced vital capacity (FVC), and Diffusing capacity for carbon monoxide (DLCO) <50% predicted (corrected for hemoglobin) for patients who have not received thoracic or mantle irradiation. For patients who have received thoracic or mantle irradiation, FEV1 and FVC <70% predicted or DLCO < 50 of predicted. For children unable to perform Pulmonary function tests (PFTs) because of developmental stage pulse oximetry < 92% on Room air (RA).
Poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy). Alanine aminotransferase (ALT) or Aspartate transaminase (AST) > 3 x laboratory upper normal limits.
Poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 60 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl) Multiply by another factor of 0.85 if female Intended for ages 18-110, serum creatinine 0.6-7 mg/dl For patients <18 years: creatinine clearance (CrCl) will be estimated by the Schwartz formula. A measured CrCl or a Glomerular filtration rate (GFR) may be substituted to determine the subject's CrCl.
Schwartz equation: CrCl (ml/min/1.73m2)=[length (cm) x k] /serum creatinine K = 0.45 for infants 1 to 52 weeks old k = 0.55 for children 1 to 13 years old k = 0.55 for adolescent females 13-18 years old k = 0.7 for adolescent males 13-18 years old
HIV-positive
Positive leukocytotoxic crossmatch Specifically, complement dependent cytotoxicity and flow cytometric crossmatch assays must be negative, and the mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be <3000. Consult with PI for the clinical significance of any anti-donor antibody.
Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception or who are breastfeeding
Uncontrolled viral, bacterial, or fungal infections (currently taking medication and have progression of clinical symptoms)
Patients with symptoms consistent with Respiratory syncytial virus (RSV), influenza A, B, or parainfluenza at the time of enrollment will be assayed for the above viruses and if positive are not eligible for the trial until they are no longer symptomatic (patients may have continued assay positivity for a period of time post resolution of symptoms secondary to the nature of the assay

Name	Affiliation	Role
Heather Symons, MD, MHS	SKCCC Johns Hopkins Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital of Colorado		Aurora	Colorado	80045	United States
Nemours Alfred I. DuPont Hospital for Children

PubMed Identifier	Type	Citation	Retractions
37257193	Derived	Fierro-Pineda JC, Tsai HL, Blackford A, Cluster A, Caywood E, Dalal J, Davis J, Egeler M, Huo J, Hudspeth M, Keating A, Kelly SS, Krueger J, Lee D, Lehmann L, Madden L, Oshrine B, Pulsipher MA, Fry T, Symons HJ. Prospective PTCTC trial of myeloablative haplo-BMT with posttransplant cyclophosphamide for pediatric acute leukemias. Blood Adv. 2023 Sep 26;7(18):5639-5648. doi: 10.1182/bloodadvances.2023010281.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS): Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with acute lymphocytic leukemia (ALL) and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: total body irradiation (TBI) 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Apr 20, 2017

Arm/Group Information

ID	Title	Description
BG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS): Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with acute lymphocytic leukemia (ALL) and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: total body irradiation (TBI) 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Units	Counts
Participants	BG00032

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cumulative Incidence of Non-relapse Mortality

Cumulative incidence (measured as a percentage) of non-relapse mortality at 180 days following myeloablative, Human Leukocyte Antigen (HLA)-mismatched bone marrow transplant (BMT) for patients with high risk hematologic malignancies.

Posted

Number

percent

Day 180

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS): Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with acute lymphocytic leukemia (ALL) and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: total body irradiation (TBI) 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Units	Counts
Participants	OG00032

Title

Denominators

Categories

Title	Measurements
	OG0000

Secondary

Number of Participants With Donor Cell Engraftment

Number of Participants with Donor Cell Engraftment at Day 60 following myeloablative, HLA-mismatched BMT.

Posted

Count of Participants

Participants

Day 60

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Units	Counts
Participants

Secondary

Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4

Cumulative incidence (measured as a percentage) of acute GVHD grades 2-4 (overall) and grades 3-4 (severe).

Posted

Number

percent

100 days

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Units	Counts
Participants

Secondary

Cumulative Incidence of Chronic GVHD

Cumulative incidence (measured as a percentage) of chronic graft versus host disease (GVHD).

Posted

Number

percent

2 years

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Units	Counts
Participants

Secondary

Primary and Secondary Graft Failure

Incidence (measured as a percentage) of primary and secondary graft failure.

Posted

Number

percentage of graft failure

2 years

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Units	Counts
Participants

Secondary

Steroid and Non-steroid Immunosuppressants

Number of participants who used steroid and non-steroid immunosuppressants to treat GVHD.

Posted

Count of Participants

Participants

Two Years

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Units	Counts
Participants

Secondary

Steroid and Non-steroid Immunosuppressants Use Duration

Duration of use of steroid and non-steroid immunosuppressants (in months) to treat GVHD.

Four participants used immunosuppressants. Four used steroids and 2 of the 4 also used non-steroid. Duration of use for 3 participants using steroids was not recorded. One participant using non-steroid was not recorded.

Posted

Number

months

Two Years

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Secondary

Survival

Estimate incidence of overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), event-free survival, and relapse-free GVHD-free survival (GRFS) in patients receiving myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies at 1 year. Incidence as a percentage.

Posted

Number

percent

up to 1 years

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Secondary

Survival

Posted

Number

percent

up to 2 years

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Secondary

Immune Reconstitution

Characterize immune reconstitution post myeloablative haploidentical BMT with Post transplantation cyclophosphamide (PT/Cy).

Blood samples collected were not analyzed due to lack of funding. No data was generated.

Posted

Two Years

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS): Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with acute lymphocytic leukemia (ALL) and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: total body irradiation (TBI) 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Secondary

Time to Neutrophil and Platelet Recovery

Time to neutrophil and platelet recovery in median days

Posted

Median

Full Range

days

100 days

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Units	Counts
Participants

Secondary

Incidence of Donor Cell Engraftment

Incidence of donor cell engraftment measured as the percentage of donor cell engraftment.

Posted

Number

percentage of donor cell engraftment

60 days

ID	Title	Description
OG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with AML and MDS: Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with ALL and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Haploidentical BMT With PTCy for Acute Leukemias and MDS	Patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS): Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV For patients with acute lymphocytic leukemia (ALL) and lymphoblastic lymphoma: Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV Days -3 through -1: total body irradiation (TBI) 200 Centigray (cGy) twice a day for 3 days All patients Day 0: Infuse unmanipulated bone marrow Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day Day +30: Assess chimerism and disease status in bone marrow Day +35: Discontinue MMF Day +60: Assess chimerism and disease status in bone marrow Day 180: Discontinue tacrolimus Cyclophosphamide: Chemotherapy administration TBI: Radiation Therapy Busulfan: Chemotherapy Administered Unmanipulated Bone Marrow: Bone Marrow Transplant Tacrolimus: Immunosuppressive Drug Administered Mycophenolate mofetil: Immunosuppressive Drug Administered	8	32	14	32	13	32

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	NCI CTCAE v4.0	Systematic Assessment	EG00020 events4 affected32 at risk
Anorexia	Metabolism and nutrition disorders	NCI CTCAE v4.0	Systematic Assessment	EG0004 events4 affected32 at risk
Diarrhea	Gastrointestinal disorders	NCI CTCAE v4.0	Systematic Assessment	EG00010 events8 affected32 at risk
Fever	General disorders	NCI CTCAE v4.0	Systematic Assessment	EG0006 events5 affected32 at risk
Hypertension	Vascular disorders	NCI CTCAE v4.0	Systematic Assessment	EG0004 events3 affected32 at risk
Hypokalemia	Metabolism and nutrition disorders	NCI CTCAE v4.0	Systematic Assessment	EG0004 events4 affected32 at risk
Hypomagnesemia	Metabolism and nutrition disorders	NCI CTCAE v4.0	Systematic Assessment	EG0005 events5 affected32 at risk
Oral Mucositis	Gastrointestinal disorders	NCI CTCAE v4.0	Systematic Assessment	EG00013 events11 affected32 at risk
Nausea	Gastrointestinal disorders	NCI CTCAE v4.0	Systematic Assessment	EG0005 events4 affected32 at risk
Neutrophil Count Decreased	Investigations	NCI CTCAE v4.0	Systematic Assessment	EG0008 events2 affected32 at risk
Platelet Count Decreased	Investigations	NCI CTCAE v4.0	Systematic Assessment	EG00027 events3 affected32 at risk
Vomiting	Gastrointestinal disorders	NCI CTCAE v4.0	Systematic Assessment	EG00011 events8 affected32 at risk
White Blood cells decreased	Investigations	NCI CTCAE v4.0	Systematic Assessment	EG00019 events3 affected32 at risk

ID	Term
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D015470	Leukemia, Myeloid, Acute
D054429	Leukemia, Myelomonocytic, Juvenile

ID	Term
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D007951	Leukemia, Myeloid
D054437	Myelodysplastic-Myeloproliferative Diseases
D001855	Bone Marrow Diseases

ID	Term
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D002072	Butylene Glycols
D006018	Glycols
D000438	Alcohols
D008698	Mesylates
D000476	Alkanesulfonates
D017738	Alkanesulfonic Acids
D000473	Alkanes
D006839	Hydrocarbons, Acyclic
D013451	Sulfonic Acids
D013456	Sulfur Acids
D013457	Sulfur Compounds
D018942	Macrolides
D007783	Lactones
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D005227	Fatty Acids
D008055	Lipids

ID	Term
D003520	Cyclophosphamide
D002066	Busulfan
D016559	Tacrolimus
D009173	Mycophenolic Acid