Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelomonocytic, Juvenile

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Mycophenolic Acid

Tacrolimus

Busulfan

Immunosuppressive Agents

Mesna

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

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

Unmanipulated Bone Marrow

Mycophenolate mofetil

Heather Symons, MD, MHS

This is a multi-institutional phase II haploidentical T cell replete bone marrow transplant (BMT) study in children with high-risk leukemia. The myeloablative conditioning regimen prescribed will be Total body irradiation (TBI)-based for lymphoid leukemia and busulfan-based for myeloid leukemia. Our goal is to establish an easily exportable, inexpensive platform for haplotransplantation that has a safety profile equivalent to matched related and unrelated BMTs. The primary objective will be to estimate the incidence of 6-month non-relapse mortality (NRM), hypothesizing that NRM is \< 18%.

This is a phase II prospective study designed to evaluate the incidence of 6 month non- relapse mortality, safety, and feasibility of haploidentical bone marrow transplantation (BMT) after myeloablative conditioning with post-transplant Cy. Conditioning regimens include a total body irradiation (TBI)-based prep for lymphoid leukemias and a chemotherapy based prep for myeloid leukemias.

To estimate the incidence of non-relapse mortality at 180 days following myeloablative haploidentical BMT for children and young adults with high risk hematologic malignancies.

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

Pediatric Blood & Marrow Transplant Consortium (PBMTC) Phase II Myeloablative Haploidentical BMT With Post-transplantation Cyclophosphamide for Pediatric Patients With Hematologic Malignancies

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.

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

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

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

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

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

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

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.

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.

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

Time to neutrophil and platelet recovery in median days

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

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Adverse events reported at each visit during time at transplant center and up to 180 days post-transplantation.

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

Haploidentical BMT With PTCy for Acute Leukemias and MDS

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Region of Enrollment

Heather Symons, MD

Cumulative Incidence of Non-relapse Mortality

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

Number of Participants With Donor Cell Engraftment

Grades 2-4

Grades 3-4

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

Cumulative Incidence of Chronic GVHD

Primary

Secondary

Primary and Secondary Graft Failure

Steroid immunosuppressants

Non-steroid immunosuppressants

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

Steroid and Non-steroid Immunosuppressants

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.

Steroid and Non-steroid Immunosuppressants Use Duration

overall survival (OS)

progression-free survival (PFS)

disease-free survival (DFS)

event-free survival

Relapse-free GVHD-free survival (GRFS)

Survival

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

Spots Global Cancer Trial Database for unmanipulated bone marrow