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VPA Expanded UCB Transplantation for Treatment of Patients With Hematological Malignancies

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ClinicalTrials.gov Identifier: NCT03885947
Recruitment Status : Completed
First Posted : March 22, 2019
Last Update Posted : May 24, 2021
Sponsor:
Information provided by (Responsible Party):
Alla Keyzner, Icahn School of Medicine at Mount Sinai

Study Description
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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).

Condition or disease Intervention/treatment Phase
Hematological Malignancy Acute Leukemia in Remission Acute Lymphoblastic Leukemia in Remission Myelodysplastic Syndromes Non-Hodgkin Lymphoma Hodgkin Lymphoma Biological: Cord blood stem cells Drug: Valproic Acid Drug: Fludarabine Drug: cytoxan Drug: Thiotepa Biological: TBI Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Open label single arm
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Valproic Acid Expanded Cord Blood Stem Cells as an Allogeneic Donor Source for Adults With Hematological Malignancies
Actual Study Start Date : February 21, 2019
Actual Primary Completion Date : March 10, 2021
Actual Study Completion Date : March 10, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: VPA

Drug: Fludarabine
Fludarabine 150 mg/m2

Drug: cytoxan
Cytoxan 50 mg/m2

Drug: Thiotepa
Thiotepa 10 mg/m2

Biological: TBI
TBI 400cGy


Outcome Measures
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Primary Outcome Measures :
  1. Number of Infusion Reaction [ Time Frame: 42 days ]
    Safety as measured by the incidence of infusion related reactions.

  2. Number of Graft Failure [ Time Frame: 42 days ]
    Safety as measured by the incidence of graft failures.


Secondary Outcome Measures :
  1. Time to neutrophil engraftment [ Time Frame: 1 year ]
    Transplant related outcomes: time to neutrophil engraftment

  2. Time to platelets engraftment [ Time Frame: 1 year ]
    Transplant related outcomes: time to platelets engraftment

  3. Number of transplant-related mortality (TRM) [ Time Frame: 1 year ]
    Transplant related outcomes: transplant-related mortality (TRM)

  4. Number of disease free survivals [ Time Frame: 1 year ]
    Transplant related outcomes: Number of disease free survivals

  5. Number of overall survivals [ Time Frame: 1 year ]
    Transplant related outcomes: Number of overall survivals

  6. Number of participants at risk of GVHD [ Time Frame: 1 year ]
    Transplant Related Outcomes: risk of GVHD

  7. Number of infectious complications [ Time Frame: 1 year ]
    Transplant Related Outcomes: incidence of infectious complications - which is any documented bacterial, viral, or fungal infections.

  8. Time to myeloid engraftment [ Time Frame: 42 days ]
    Assess the kinetics of engraftment and immune reconstitution by assessing time to myeloid engraftment

  9. Time to lymphoid engraftment [ Time Frame: 42 days ]
    Assess the kinetics of engraftment and immune reconstitution by assessing time to lymphoid engraftment

  10. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03885947


Locations
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United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Alla Keyzner
Investigators
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Principal Investigator: Alla Keyzner, MD Icahn School of Medicine at Mount Sinai
More Information
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Responsible Party: Alla Keyzner, Assistant Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT03885947    
Other Study ID Numbers: GCO 14-0451
First Posted: March 22, 2019    Key Record Dates
Last Update Posted: May 24, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alla Keyzner, Icahn School of Medicine at Mount Sinai:
Hematological Malignancies
Expanded Umbilical Cord
Allogeneic Stem Cell Transplant
Leukemia
Lymphoma
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Neoplasms
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Lymphoid
Neoplasms by Site
 Fludarabine
Cyclophosphamide
Thiotepa
Valproic Acid
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Anticonvulsants
Enzyme Inhibitors