Acute Leukemia in Remission, Acute Lymphoblastic Leukemia in Remission, Hematological Malignancy, Hodgkin Lymphoma, Myelodysplastic Syndromes, Non-Hodgkin Lymphoma
Conditions
Keywords
Hematological Malignancies, Expanded Umbilical Cord, Allogeneic Stem Cell Transplant, Leukemia, Lymphoma
Brief summary
In this Phase I study, the study team will evaluate the safety of Valproic Acid (VPA) expanded cord blood stem cells defined by the lack of serious infusion reactions or graft failure in patients with hematological malignancies undergoing umbilical cord blood transplantation. Moreover, the study team will also evaluate time to neutrophil and platelet engraftment as well as transplant related outcomes such as graft versus host disease (GVHD), treatment related mortality (TRM), and overall survival (OS).
Detailed description
This is a phase I trial for safety of VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation. The primary endpoint of the study is safety as defined by the incidence of infusion reactions and graft failure, lack of neutrophil engraftment by day +42. The trial will consist of two cohorts. First cohort of 5-7 patients, will undergo double umbilical cord blood (UCB) transplantation. One UCB unit will undergo CD34 selection followed VPA based expansion. CD34 negative portion of that unit will be cryopreserved to be infused later following infusion of the expanded portion. Infusion of the second unmanipulated UCB will follow it. Preparative regimen is Fludarabine 150 mg/m2/Cytoxan 50 mg/m2/Thiotepa 10 mg/m2/TBI 400cGy. Following successful engraftment in the first cohort, second cohort (10 patients) will only receive single manipulated unit. Otherwise, patients will receive standard allogeneic stem cell transplantation care.
Interventions
BIOLOGICALCord blood stem cells
CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood .
DRUGValproic Acid
Valproic Acid (VPA) expanded cord blood stem cells
DRUGFludarabine
Fludarabine 150 mg/m2
DRUGcytoxan
Cytoxan 50 mg/m2
DRUGThiotepa
Thiotepa 10 mg/m2
BIOLOGICALTBI
TBI 400cGy
Sponsors
Alla Keyzner
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label single arm
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Disease criteria: Patients with the following hematological malignancies: * Acute Myeloid Leukemia (AML) in complete remission (CR) * Acute Lymphoblastic Leukemia (ALL) in complete remission (CR) * Myelodysplastic Syndrome (MDS) requiring intensive chemotherapy * Non-Hodgkin lymphoma in complete or partial remission * Hodgkin lymphoma in complete or partial remission Age Criteria: \- 18 years up to 65 years. Organ Function and Performance Status Criteria: \- Performance status score: Karnofsky Score ≥60 Adequate major organ function defined as: * Left ventricular ejection fraction ≥40% * Pulmonary function test demonstrating DLCO ≥50% predicted and corrected for hemoglobin * Serum creatinine ≤ 2 mg/dL * Transaminases ≤ 3x ULN * Bilirubin ≤3x ULN except for in case of Gilbert's syndrome or ongoing hemolysis * Ability to understand and the willingness to sign a written informed consent document Donor availability: -Lack of suitable HLA matched related or unrelated donor available within 30 days or less if BMT is urgent in the opinion of the transplant physician.
Exclusion criteria
* Progressive, persistent disease or active malignancy * Greater than 10% blasts on bone marrow biopsy in patients with MDS * Chemotherapy naïve * History of myelofibrosis * Presence of Bone Marrow Fibrosis grade 2/3 * Presence of donor specific anti-HLA antibodies against available UCB units at A, B, C or DR loci, with a mean fluorescence intensity (MFI)\>1000 * History of prior allogeneic stem cell transplantation * Uncontrolled viral, bacterial or fungal infection * History of HIV infection * Presence of active CNS disease at the time of transplantation * Pregnant or breastfeeding female * Inability or unwillingness to use effective birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Infusion Reaction | 42 days | Safety as measured by the incidence of infusion related reactions. |
| Number of Graft Failure | 42 days | Safety as measured by the incidence of graft failures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of transplant-related mortality (TRM) | 1 year | Transplant related outcomes: transplant-related mortality (TRM) |
| Number of disease free survivals | 1 year | Transplant related outcomes: Number of disease free survivals |
| Number of overall survivals | 1 year | Transplant related outcomes: Number of overall survivals |
| Number of participants at risk of GVHD | 1 year | Transplant Related Outcomes: risk of GVHD |
| Time to neutrophil engraftment | 1 year | Transplant related outcomes: time to neutrophil engraftment |
| Time to myeloid engraftment | 42 days | Assess the kinetics of engraftment and immune reconstitution by assessing time to myeloid engraftment |
| Time to lymphoid engraftment | 42 days | Assess the kinetics of engraftment and immune reconstitution by assessing time to lymphoid engraftment |
| Change in T cell count | Baseline and 42 days | Assess the kinetics of engraftment and immune reconstitution by assessing the T cell count at 42 days as compared to baseline |
| Number of infectious complications | 1 year | Transplant Related Outcomes: incidence of infectious complications - which is any documented bacterial, viral, or fungal infections. |
| Time to platelets engraftment | 1 year | Transplant related outcomes: time to platelets engraftment |
Countries
United States
Outcome results
None listed