VPA Expanded UCB Transplantation for Treatment of Patients With Hematological Malignancies

Myelodysplastic Syndromes Clinical Trial

Official title:

Phase I Study of Valproic Acid Expanded Cord Blood Stem Cells as an Allogeneic Donor Source for Adults With Hematological Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03885947
• Other study ID #: GCO 14-0451
• Status: Completed
• Phase: Phase 1
• Start date: February 21, 2019
• Est. completion date: March 10, 2021

Study information

• Verified date: May 2021
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: March 10, 2021
• Est. primary completion date: March 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Leukemia in Remission
• Acute Lymphoblastic Leukemia in Remission
• Hematologic Neoplasms
• Hematological Malignancy
• Hodgkin Lymphoma
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Neoplasms
• Non-Hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Cord blood stem cells
CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood .

Drug:
• Valproic Acid
Valproic Acid (VPA) expanded cord blood stem cells
• Fludarabine
Fludarabine 150 mg/m2
• cytoxan
Cytoxan 50 mg/m2
• Thiotepa
Thiotepa 10 mg/m2

Biological:
• TBI
TBI 400cGy

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Alla Keyzner

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Infusion Reaction	Safety as measured by the incidence of infusion related reactions.	42 days
Primary	Number of Graft Failure	Safety as measured by the incidence of graft failures.	42 days
Secondary	Time to neutrophil engraftment	Transplant related outcomes: time to neutrophil engraftment	1 year
Secondary	Time to platelets engraftment	Transplant related outcomes: time to platelets engraftment	1 year
Secondary	Number of transplant-related mortality (TRM)	Transplant related outcomes: transplant-related mortality (TRM)	1 year
Secondary	Number of disease free survivals	Transplant related outcomes: Number of disease free survivals	1 year
Secondary	Number of overall survivals	Transplant related outcomes: Number of overall survivals	1 year
Secondary	Number of participants at risk of GVHD	Transplant Related Outcomes: risk of GVHD	1 year
Secondary	Number of infectious complications	Transplant Related Outcomes: incidence of infectious complications - which is any documented bacterial, viral, or fungal infections.	1 year
Secondary	Time to myeloid engraftment	Assess the kinetics of engraftment and immune reconstitution by assessing time to myeloid engraftment	42 days
Secondary	Time to lymphoid engraftment	Assess the kinetics of engraftment and immune reconstitution by assessing time to lymphoid engraftment	42 days
Secondary	Change in T cell count	Assess the kinetics of engraftment and immune reconstitution by assessing the T cell count at 42 days as compared to baseline	Baseline and 42 days