VPA Expanded UCB Transplantation for Treatment of Patients With Hematological Malignancies

NCT03885947 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: GCO 14-0451
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Number of Infusion Reaction

  Safety as measured by the incidence of infusion related reactions.

  42 days

• Number of Graft Failure

  Safety as measured by the incidence of graft failures.

  42 days

Secondary Outcomes (10)

• Time to neutrophil engraftment

  1 year

• Time to platelets engraftment

  1 year

• Number of transplant-related mortality (TRM)

  1 year

• Number of disease free survivals

  1 year

• Number of overall survivals

  1 year

Study Arms (1)

VPA expanded cord blood stem cells

EXPERIMENTAL

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; Drug: Valproic Acid; Drug: Fludarabine; Drug: cytoxan; Drug: Thiotepa; Biological: TBI

Interventions

Cord blood stem cells BIOLOGICAL

CD34 selected VPA expanded umbilical cord blood cells used in combination with or without unmanipulated umbilical cord blood .

VPA expanded cord blood stem cells

Valproic Acid DRUG

Valproic Acid (VPA) expanded cord blood stem cells

Also known as: VPA

VPA expanded cord blood stem cells

Fludarabine DRUG

Fludarabine 150 mg/m2

VPA expanded cord blood stem cells

cytoxan DRUG

Cytoxan 50 mg/m2

VPA expanded cord blood stem cells

Thiotepa DRUG

Thiotepa 10 mg/m2

VPA expanded cord blood stem cells

TBI BIOLOGICAL

TBI 400cGy

VPA expanded cord blood stem cells

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alla Keyzner: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia; Lymphoma

Interventions

Valproic Acid; fludarabine; Cyclophosphamide; Thiotepa

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Alla Keyzner, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Open label single arm

Study Record Dates

• First Submitted: March 20, 2019
• First Posted: March 22, 2019
• Study Start: February 21, 2019
• Primary Completion: March 10, 2021
• Study Completion: March 10, 2021
• Last Updated: May 24, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)