Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen
- Conditions
- Hematological Malignancies
- Interventions
- Biological: G-CSFRadiation: Total lymphoid irradiationBiological: Lymphocyte infusionsDevice: CliniMACS
- Registration Number
- NCT02199041
- Lead Sponsor
- St. Jude Children's Research Hospital
- Brief Summary
In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA)-matched related/sibling donor (MSD), matched unrelated donor (MURD) or killer-immunoglobulin receptors (KIR) ligand mismatched haploidentical donor identified, will receive a combined T cell depleted (TCD) haploidentical peripheral blood stem cell (PBSC) and unrelated umbilical cord blood transplantation (UCBT) using a total lymphoid irradiation (TLI) based preparative regimen.
Primary objective:
* To estimate the incidence of donor derived neutrophil engraftment by day +42 post-transplant for participants with high-risk hematologic malignancies undergoing a total lymphoid irradiation (TLI)-based hematopoietic cell transplantation (HCT) using a T cell depleted (TCI) haploidentical donor peripheral blood stem cell (PBSC) donor combined with an unrelated umbilical cord blood (UCB) donor.
Secondary objectives:
* Estimate the incidence of malignant relapse, event-free survival (EFS), and overall survival (OS) at one-year post-transplantation.
* Estimate the incidence and severity of acute and chronic graft versus host disease (GVHD) in the first 100 days after transplantation.
* Estimate the incidence of secondary graft failure transplant related mortality (TRM) and transplant related morbidity in the first 100 days after HCT.
- Detailed Description
Prior to stem cell infusion, participants will receive a preparative regimen of total lymphoid irradiation (TLI), fludarabine, cyclophosphamide, melphalan, and thiotepa to prepare their bone marrow. Thereafter, they will receive a hematopoietic cell graft from a haploidentical donor and an unrelated umbilical cord blood donor. Post-transplantation immunosuppressive treatment will include tacrolimus and mycophenolate mofetil.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Thiotepa Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment Fludarabine Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment Cyclophosphamide Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment G-CSF Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment Total lymphoid irradiation Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment Lymphocyte infusions Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment CliniMACS Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment Melphalan Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment Mesna Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment Mycophenolate mofetil Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment Tacrolimus Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System. Treatment Methylprednisolone Interventions: cyclophosphamide, thiotepa, fludarabine, melphalan, mesna, granulocyte colony-stimulating factor (G-CSF), mycophenolate mofetil, tacrolimus, methylprednisolone, total lymphoid irradiation, and lymphocyte infusions. Cells for infusion are prepared using the CliniMACS System.
- Primary Outcome Measures
Name Time Method Number of Participants With Neutrophil Engraftment Until day 42 post-transplant Neutrophil engraftment is defined as absolute neutrophil count (ANC) recovery of ≥ 0.5 x 10\^9/L (500/mm\^3) for three consecutive laboratory values obtained on different days (derived from either donor). Date of engraftment is the date of the first of the three consecutive laboratory values. The number of patients engrafted by day +42 post-transplant is provided.
- Secondary Outcome Measures
Name Time Method Number of Participants With Overall Survival (OS) One year after transplantation The Kaplan-Meier estimate of OS with relapse, death due to any cause and graft failure as events along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\\kme) available in the Department of Biostatistics at St. Jude, where OS = min (date of last follow-up, date of death) - date of hematopoietic cell transplantation (HCT) and all participants surviving after 1 year post-transplant will be considered as censored.
Due to the early close of the study, a small number of patients were enrolled. Subsequently, the number of patients who did not die at 1 year post-transplant is provided.Number of Participants With Transplant-related Mortality (TRM) 100 days after transplantation TRM is any death in remission and related to protocol therapy. The cumulative incidence of TRM was estimated using the Kalbfleisch-Prentice method. Deaths before day 100 because of other reasons are the completing events.
Due to the early close of the study, a small number of patients were enrolled. Subsequently, the number of patients who experienced TRM is provided.Number of Participants With Malignant Relapse One year after transplantation Relapse was evaluated using standard World Health Organization (WHO) criteria for each disease. The estimate of cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Relapse defined as the recurrence of original disease. Death is the competing risk event. The analysis will be implemented using Statistical Analysis System (SAS) macro (bmacro252-Excel2007\\cin).
Due to the early close of the study, a small number of patients were enrolled. Subsequently, the number of patients who experienced malignant relapse is providedNumber of Participants With Transplant-related Morbidity 100 days after transplantation Any patient who had adverse events listed either as probable or definite in the first 100 days post-transplant are counted as transplant-related morbidity. The cumulative incidence of transplant-related morbidity will be estimated using the Kalbfleisch-Prentice method. Deaths before day 100 are the competing risk events.
Due to the early close of the study, a small number of patients were enrolled. Subsequently, the number of patients who experienced at least one-transplant-related morbidity is provided.Number of Participants With Event-free Survival (EFS) One year after transplantation The Kaplan-Meier estimate of EFS with relapse, death due to any cause and graft failure as events along with their standard errors will be calculated using the SAS macro (bmacro251-Excel2007\\kme) available in the Department of Biostatistics at St. Jude, where EFS = min (date of last follow-up, date of relapse, date of graft failure, date of death due to any cause) - date of transplant, and all participants surviving at the time of analysis without events will be censored. The number of participants who did not experience any of these events through one year post-transplant is given.
Due to the early close of the study, a small number of patients were enrolled. Subsequently, the number of patients who did not experience any events defined above is provided.Number of Participants With Secondary Graft Failure 100 days after transplantation The cumulative incidence of secondary graft failure will be estimated using the Kalbfleisch-Prentice method. Deaths due to toxicity and relapse before day 100 are the competing events.
Secondary graft failure or graft rejection will be defined as no evidence of donor chimerism by umbilical cord blood (UCB) and/or haploidentical donor (\<10%), or too few cells to perform adequate chimerism analysis, in research participants with prior neutrophil engraftment.
Due to the early close of the study, a small number of patients were enrolled. Subsequently, the number of patients who experienced secondary graft failure is provided.Number of Participants by Severity With Acute Graft Versus Host Disease (GVHD) in the First 100 Days After HCT 100 days after transplantation Cumulative incidence of acute GVHD was estimated using Kalbfleisch-Prentice method. Death is the competing risk event. SAS macro (bmacro252-Excel2007\\cin) available at St. Jude was used for analysis. Severity of GVHD and stage were determined using the Clinical Oncology Group (COG) Stem Cell Committee Consensus Guidelines for establishing organ stage and overall grade of acute GVHD. Participants are graded on a scale from I to IV, with I being mild and IV being severe.
Overall Clinical Grade (based on the highest stage obtained):
Grade 0: No stage 1-4 of any organ. Grade I: Stage 1-2 skin and no liver or gut involvement. Grade II: Stage 3 skin, or Stage I liver involvement, or Stage 1 gastrointestinal (GI).
Grade III: Stage 0-3 skin, with Stage 2-3 liver, or Stage 2-3 GI. Grade IV: Stage 4 skin, liver or GI involvement.
Due to early close of study, a small number of patients were enrolled. The number of patients who experienced acute GVHD is provided.Number of Participants by Severity With Chronic Graft Versus Host Disease (GVHD) in the First 100 Days After HCT 100 days after transplantation Cumulative incidence of acute and chronic GVHD was estimated using Kalbfleisch-Prentice method. Death is competing risk event. SAS macro (bmacro252-Excel2007\\cin) available St. Jude was used for such analysis. Severity of chronic GVHD was evaluated using National Institutes of Health (NIH) Consensus Global Severity Scoring. Mild is considered a better outcome with severe being the worst.
Criteria for grading chronic GVHD:
Mild: 1-2 organs/sites, maximum organ score of 1, and lung score of 1. Moderate: 3 or more organs/sites and maximum organ score of 1 and lung score of 1, OR at least 1 organ/site and maximum organ score of 2 and lung score of 1. Severe: At least 1 organ/site and maximum organ score of 3 and lung score of 2-3.
Due to the early close of the study, a small number of patients were enrolled. Subsequently, the number of patients who experienced chronic GVHD is provided.
Trial Locations
- Locations (1)
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States