Trial Outcomes & Findings for Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies (NCT NCT02120157)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

Day 180

Results posted on

2021-11-26

Participant Flow

Three patients screen failed due to: One patient could not report on whether the marrow is cellular or at least 20 percent cellularity, one patient had poor liver function, and the one patient's Alanine aminotransferase (ALT) was over the study limit.

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	32
Overall Study Completed 180 Days	30
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Death	8

Baseline Characteristics

Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Age, Continuous	12 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment Canada	7 Participants n=5 Participants
Region of Enrollment United States	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 180

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.

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Cumulative Incidence of Non-relapse Mortality	0 percent

SECONDARY outcome

Timeframe: Day 60

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

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Number of Participants With Donor Cell Engraftment	27 Participants

SECONDARY outcome

Timeframe: 100 days

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

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4 Grades 2-4	10 percent
Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4 Grades 3-4	0 percent

SECONDARY outcome

Timeframe: 2 years

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

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Cumulative Incidence of Chronic GVHD	11 percent

SECONDARY outcome

Timeframe: 2 years

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

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Primary and Secondary Graft Failure Primary	16 percentage of graft failure
Primary and Secondary Graft Failure Secondary	0 percentage of graft failure

SECONDARY outcome

Timeframe: Two Years

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

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Steroid and Non-steroid Immunosuppressants Steroid immunosuppressants	4 Participants
Steroid and Non-steroid Immunosuppressants Non-steroid immunosuppressants	2 Participants

SECONDARY outcome

Timeframe: Two Years

Population: 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.

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

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=2 Participants 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
Steroid and Non-steroid Immunosuppressants Use Duration Steroid immunosuppressants	18 months
Steroid and Non-steroid Immunosuppressants Use Duration Non-steroid immunosuppressants	19 months

SECONDARY outcome

Timeframe: up to 1 years

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.

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Survival overall survival (OS)	77 percent
Survival progression-free survival (PFS)	68 percent
Survival disease-free survival (DFS)	68 percent
Survival event-free survival	68 percent
Survival Relapse-free GVHD-free survival (GRFS)	65 percent

SECONDARY outcome

Timeframe: up to 2 years

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 2 years. Incidence as a percentage.

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Survival overall survival (OS)	73 percent
Survival progression-free survival (PFS)	64 percent
Survival disease-free survival (DFS)	64 percent
Survival event-free survival	64 percent
Survival Relapse-free GVHD-free survival (GRFS)	52 percent

SECONDARY outcome

Timeframe: Two Years

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 100 days

Time to neutrophil and platelet recovery in median days

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Time to Neutrophil and Platelet Recovery neutrophil	22 days Interval 14.0 to 58.0
Time to Neutrophil and Platelet Recovery platelet	21 days Interval 12.0 to 44.0

SECONDARY outcome

Timeframe: 60 days

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

Outcome measures

Outcome measures
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 Participants 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
Incidence of Donor Cell Engraftment	84 percentage of donor cell engraftment

Adverse Events

Haploidentical BMT With PTCy for Acute Leukemias and MDS

Serious events: 14 serious events

Other events: 13 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 participants at risk 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
General disorders Fever	9.4% 3/32 • Number of events 3 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Hepatobiliary disorders Veno-occlusive Disease/ Hepatic Sinusoidal Obstruction Syndrome	12.5% 4/32 • Number of events 4 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Surgical and medical procedures Graft Failure	9.4% 3/32 • Number of events 3 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Surgical and medical procedures Acute GVHD	3.1% 1/32 • Number of events 1 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Infections and infestations Broviac Cather Infection	3.1% 1/32 • Number of events 1 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Blood and lymphatic system disorders Intracranial Hemorrhage	3.1% 1/32 • Number of events 1 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Renal and urinary disorders Cystitis	3.1% 1/32 • Number of events 1 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.

Other adverse events

Other adverse events
Measure	Haploidentical BMT With PTCy for Acute Leukemias and MDS n=32 participants at risk 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
Blood and lymphatic system disorders Anemia	12.5% 4/32 • Number of events 20 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Metabolism and nutrition disorders Anorexia	12.5% 4/32 • Number of events 4 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Gastrointestinal disorders Diarrhea	25.0% 8/32 • Number of events 10 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
General disorders Fever	15.6% 5/32 • Number of events 6 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Vascular disorders Hypertension	9.4% 3/32 • Number of events 4 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Metabolism and nutrition disorders Hypokalemia	12.5% 4/32 • Number of events 4 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Metabolism and nutrition disorders Hypomagnesemia	15.6% 5/32 • Number of events 5 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Gastrointestinal disorders Oral Mucositis	34.4% 11/32 • Number of events 13 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Gastrointestinal disorders Nausea	12.5% 4/32 • Number of events 5 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Investigations Neutrophil Count Decreased	6.2% 2/32 • Number of events 8 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Investigations Platelet Count Decreased	9.4% 3/32 • Number of events 27 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Gastrointestinal disorders Vomiting	25.0% 8/32 • Number of events 11 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.
Investigations White Blood cells decreased	9.4% 3/32 • Number of events 19 • Adverse event data was collected up to 180 days after transplantation. Mortality was observed for up to 2 year post-intervention. Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.

Additional Information

Heather Symons, MD

Johns Hopkins University

Phone: 410-502-9961

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place