VPA Expanded UCB Transplantation for Treatment of Patients With Hematological Malignancies

May 20, 2021 updated by: Alla Keyzner

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VPA expanded 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
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
Other Names:
  • VPA
Drug: Fludarabine
Fludarabine 150 mg/m2
Drug: cytoxan
Cytoxan 50 mg/m2
Drug: Thiotepa
Thiotepa 10 mg/m2
Biological: TBI
TBI 400cGy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Infusion Reaction
Time Frame: 42 days
Safety as measured by the incidence of infusion related reactions.
42 days
Number of Graft Failure
Time Frame: 42 days
Safety as measured by the incidence of graft failures.
42 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to neutrophil engraftment
Time Frame: 1 year
Transplant related outcomes: time to neutrophil engraftment
1 year
Time to platelets engraftment
Time Frame: 1 year
Transplant related outcomes: time to platelets engraftment
1 year
Number of transplant-related mortality (TRM)
Time Frame: 1 year
Transplant related outcomes: transplant-related mortality (TRM)
1 year
Number of disease free survivals
Time Frame: 1 year
Transplant related outcomes: Number of disease free survivals
1 year
Number of overall survivals
Time Frame: 1 year
Transplant related outcomes: Number of overall survivals
1 year
Number of participants at risk of GVHD
Time Frame: 1 year
Transplant Related Outcomes: risk of GVHD
1 year
Number of infectious complications
Time Frame: 1 year
Transplant Related Outcomes: incidence of infectious complications - which is any documented bacterial, viral, or fungal infections.
1 year
Time to myeloid engraftment
Time Frame: 42 days
Assess the kinetics of engraftment and immune reconstitution by assessing time to myeloid engraftment
42 days
Time to lymphoid engraftment
Time Frame: 42 days
Assess the kinetics of engraftment and immune reconstitution by assessing time to lymphoid engraftment
42 days
Change in T cell count
Time Frame: 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
Baseline and 42 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alla Keyzner

Investigators

  • Principal Investigator: Alla Keyzner, MD, Icahn School of Medicine at Mount Sinai

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 21, 2019

Primary Completion (Actual)

March 10, 2021

Study Completion (Actual)

March 10, 2021

Study Registration Dates

First Submitted

March 20, 2019

First Submitted That Met QC Criteria

March 20, 2019

First Posted (Actual)

March 22, 2019

Study Record Updates

Last Update Posted (Actual)

May 24, 2021

Last Update Submitted That Met QC Criteria

May 20, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 14-0451

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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