Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies
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|ClinicalTrials.gov Identifier: NCT02120157|
Recruitment Status : Completed
First Posted : April 22, 2014
Results First Posted : April 18, 2019
Last Update Posted : November 26, 2021
|Condition or disease||Intervention/treatment||Phase|
|Myeloablative Conditioning HLA-mismatched Bone Marrow Transplantation Graft Survival Transplantation, Bone Marrow||Drug: Cyclophosphamide Radiation: TBI Drug: Busulfan Other: Unmanipulated Bone Marrow Drug: Tacrolimus Drug: Mycophenolate mofetil||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pediatric Blood & Marrow Transplant Consortium (PBMTC) Phase II Myeloablative Haploidentical BMT With Post-transplantation Cyclophosphamide for Pediatric Patients With Hematologic Malignancies|
|Actual Study Start Date :||July 2, 2015|
|Actual Primary Completion Date :||June 15, 2018|
|Actual Study Completion Date :||October 1, 2020|
Experimental: 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
Other Name: Cy
Other Name: Bu
Other: Unmanipulated Bone Marrow
Bone Marrow Transplant
Immunosuppressive Drug Administered
Other Name: tacro
Drug: Mycophenolate mofetil
Immunosuppressive Drug Administered
Other Name: MMF
- Cumulative Incidence of Non-relapse Mortality [ Time Frame: 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.
- Number of Participants With Donor Cell Engraftment [ Time Frame: Day 60 ]Number of Participants with Donor Cell Engraftment at Day 60 following myeloablative, HLA-mismatched BMT.
- Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4 [ Time Frame: 100 days ]Cumulative incidence (measured as a percentage) of acute GVHD grades 2-4 (overall) and grades 3-4 (severe).
- Cumulative Incidence of Chronic GVHD [ Time Frame: 2 years ]Cumulative incidence (measured as a percentage) of chronic graft versus host disease (GVHD).
- Primary and Secondary Graft Failure [ Time Frame: 2 years ]Incidence (measured as a percentage) of primary and secondary graft failure.
- Steroid and Non-steroid Immunosuppressants [ Time Frame: Two Years ]Number of participants who used steroid and non-steroid immunosuppressants to treat GVHD.
- Steroid and Non-steroid Immunosuppressants Use Duration [ Time Frame: Two Years ]Duration of use of steroid and non-steroid immunosuppressants (in months) to treat GVHD.
- Survival [ Time Frame: 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.
- Survival [ Time Frame: 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.
- Immune Reconstitution [ Time Frame: Two Years ]Characterize immune reconstitution post myeloablative haploidentical BMT with Post transplantation cyclophosphamide (PT/Cy).
- Time to Neutrophil and Platelet Recovery [ Time Frame: 100 days ]Time to neutrophil and platelet recovery in median days
- Incidence of Donor Cell Engraftment [ Time Frame: 60 days ]Incidence of donor cell engraftment measured as the percentage of donor cell engraftment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02120157
|United States, Colorado|
|Children's Hospital of Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Delaware|
|Nemours Alfred I. DuPont Hospital for Children|
|Wilmington, Delaware, United States, 19803|
|United States, Florida|
|All Children's Hospital Johns Hopkins Medicine|
|Saint Petersburg, Florida, United States, 33701|
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|United States, Missouri|
|Washington University in St. Louis|
|Saint Louis, Missouri, United States, 63110|
|United States, North Carolina|
|Levine Cancer Center|
|Charlotte, North Carolina, United States, 28203|
|United States, South Carolina|
|Medical University of South Carolina|
|Charleston, South Carolina, United States, 29423|
|Canada, British Columbia|
|British Columbia Children's Hospital|
|Vancouver, British Columbia, Canada, V6H 3V4|
|Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Principal Investigator:||Heather Symons, MD, MHS||SKCCC Johns Hopkins Hospital|