VPA Expanded UCB Transplantation for Treatment of Patients With Hematological Malignancies

Phase 1

Completed

• Conditions: Hematological Malignancy; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia in Remission; Myelodysplastic Syndromes; Hodgkin Lymphoma; Non-Hodgkin Lymphoma
• Interventions: Biological: Cord blood stem cells; Drug: Valproic Acid; Drug: Fludarabine; Drug: cytoxan; Drug: Thiotepa; Biological: TBI

• Registration Number: NCT03885947
• Lead Sponsor: Alla Keyzner

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 engraft...

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....

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2019-02-21
• Study First Submitted: 2019-03-20
• Study First Submitted QC: 2019-03-20
• Study First Posted: 2019-03-22
• Primary Completion: 2021-03-10
• Study Completion: 2021-03-10
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-20
• Last Update Posted: 2021-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
VPA expanded cord blood stem cells	TBI	CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood for patients with hematological malignancies undergoing allogeneic stem cell transplantation. VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation
VPA expanded cord blood stem cells	Cord blood stem cells	CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood for patients with hematological malignancies undergoing allogeneic stem cell transplantation. VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation
VPA expanded cord blood stem cells	Valproic Acid	CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood for patients with hematological malignancies undergoing allogeneic stem cell transplantation. VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation
VPA expanded cord blood stem cells	cytoxan	CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood for patients with hematological malignancies undergoing allogeneic stem cell transplantation. VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation
VPA expanded cord blood stem cells	Fludarabine	CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood for patients with hematological malignancies undergoing allogeneic stem cell transplantation. VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation
VPA expanded cord blood stem cells	Thiotepa	CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood for patients with hematological malignancies undergoing allogeneic stem cell transplantation. VPA expanded cord blood stem cells in patients with hematological malignancies undergoing allogeneic stem cell transplantation

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Number of participants at risk of GVHD	1 year	Transplant Related Outcomes: risk of GVHD
Number of infectious complications	1 year	Transplant Related Outcomes: incidence of infectious complications - which is any documented bacterial, viral, or fungal infections.
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
Time to myeloid engraftment	42 days	Assess the kinetics of engraftment and immune reconstitution by assessing time to myeloid engraftment
Time to neutrophil engraftment	1 year	Transplant related outcomes: time to neutrophil engraftment
Number of transplant-related mortality (TRM)	1 year	Transplant related outcomes: transplant-related mortality (TRM)
Time to platelets engraftment	1 year	Transplant related outcomes: time to platelets 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

Trial Locations

Locations (1)

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States