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VPA Expanded UCB Transplantation for Treatment of Patients With Hematological Malignancies

Primary Purpose

Hematological Malignancy, Acute Leukemia in Remission, Acute Lymphoblastic Leukemia in Remission

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cord blood stem cells
Valproic Acid
Fludarabine
cytoxan
Thiotepa
TBI
Sponsored by
Alla Keyzner
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematological Malignancy focused on measuring Hematological Malignancies, Expanded Umbilical Cord, Allogeneic Stem Cell Transplant, Leukemia, Lymphoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

VPA expanded cord blood stem cells

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Infusion Reaction
Safety as measured by the incidence of infusion related reactions.
Number of Graft Failure
Safety as measured by the incidence of graft failures.

Secondary Outcome Measures

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

Full Information

First Posted
March 20, 2019
Last Updated
May 20, 2021
Sponsor
Alla Keyzner
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1. Study Identification

Unique Protocol Identification Number
NCT03885947
Brief Title
VPA Expanded UCB Transplantation for Treatment of Patients With Hematological Malignancies
Official Title
Phase I Study of Valproic Acid Expanded Cord Blood Stem Cells as an Allogeneic Donor Source for Adults With Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
February 21, 2019 (Actual)
Primary Completion Date
March 10, 2021 (Actual)
Study Completion Date
March 10, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Alla Keyzner

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematological Malignancy, Acute Leukemia in Remission, Acute Lymphoblastic Leukemia in Remission, Myelodysplastic Syndromes, Non-Hodgkin Lymphoma, Hodgkin Lymphoma
Keywords
Hematological Malignancies, Expanded Umbilical Cord, Allogeneic Stem Cell Transplant, Leukemia, Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Open label single arm
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
VPA expanded cord blood stem cells
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Cord blood stem cells
Intervention Description
CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood .
Intervention Type
Drug
Intervention Name(s)
Valproic Acid
Other Intervention Name(s)
VPA
Intervention Description
Valproic Acid (VPA) expanded cord blood stem cells
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Fludarabine 150 mg/m2
Intervention Type
Drug
Intervention Name(s)
cytoxan
Intervention Description
Cytoxan 50 mg/m2
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Intervention Description
Thiotepa 10 mg/m2
Intervention Type
Biological
Intervention Name(s)
TBI
Intervention Description
TBI 400cGy
Primary Outcome Measure Information:
Title
Number of Infusion Reaction
Description
Safety as measured by the incidence of infusion related reactions.
Time Frame
42 days
Title
Number of Graft Failure
Description
Safety as measured by the incidence of graft failures.
Time Frame
42 days
Secondary Outcome Measure Information:
Title
Time to neutrophil engraftment
Description
Transplant related outcomes: time to neutrophil engraftment
Time Frame
1 year
Title
Time to platelets engraftment
Description
Transplant related outcomes: time to platelets engraftment
Time Frame
1 year
Title
Number of transplant-related mortality (TRM)
Description
Transplant related outcomes: transplant-related mortality (TRM)
Time Frame
1 year
Title
Number of disease free survivals
Description
Transplant related outcomes: Number of disease free survivals
Time Frame
1 year
Title
Number of overall survivals
Description
Transplant related outcomes: Number of overall survivals
Time Frame
1 year
Title
Number of participants at risk of GVHD
Description
Transplant Related Outcomes: risk of GVHD
Time Frame
1 year
Title
Number of infectious complications
Description
Transplant Related Outcomes: incidence of infectious complications - which is any documented bacterial, viral, or fungal infections.
Time Frame
1 year
Title
Time to myeloid engraftment
Description
Assess the kinetics of engraftment and immune reconstitution by assessing time to myeloid engraftment
Time Frame
42 days
Title
Time to lymphoid engraftment
Description
Assess the kinetics of engraftment and immune reconstitution by assessing time to lymphoid engraftment
Time Frame
42 days
Title
Change in T cell count
Description
Assess the kinetics of engraftment and immune reconstitution by assessing the T cell count at 42 days as compared to baseline
Time Frame
Baseline and 42 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alla Keyzner, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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VPA Expanded UCB Transplantation for Treatment of Patients With Hematological Malignancies

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