Valproic Acid Expanded Umbilical Cord Blood Stem Cells in Treating Adult Patients with Hematological Malignancies Undergoing Donor Stem Cell Transplant

Status: Active

Description

This phase I trial studies the effects of valproic acid expanded umbilical cord blood stem cells in treating adult patients with hematological malignancies undergoing donor stem cell transplant. Expanding or growing umbilical cord blood stem cells in a laboratory using valproic acid may lead to faster white blood cell count recovery, lower the risk of infections, and improve transplant results compared to umbilical cord blood stem cells that have not been expanded.

Eligibility Criteria

Inclusion 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
  • Karnofsky score >= 60
  • Left ventricular ejection fraction >= 40%
  • Pulmonary function test demonstrating diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% predicted and corrected for hemoglobin
  • Serum creatinine =< 2 mg/dL
  • Transaminases =< 3 x upper limits of normal (ULN)
  • Bilirubin =< 3 x 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
  • Lack of suitable human leukocyte antigen (HLA) matched related or unrelated donor available within 30 days or less if bone marrow transplant (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 naive
  • History of myelofibrosis
  • Presence of bone marrow fibrosis grade 2/3
  • Presence of donor specific anti-HLA antibodies against available umbilical cord blood (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 human immunodeficiency virus (HIV) infection
  • Presence of active central nervous system (CNS) disease at the time of transplantation
  • Pregnant or breastfeeding female
  • Inability or unwillingness to use effective birth control

Locations & Contacts

New York

New York
Icahn School of Medicine at Mount Sinai
Status: Active
Contact: Alla Keyzner
Phone: 212-241-6021
Email: alla.keyzner@mssm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the safety of the valproic acid-expanded umbilical cord blood-derived CD34-positive cells valproic acid (VPA) expanded cord blood stem cells as determined by the incidence of infusion related reactions and graft failure in patients with hematological malignancies undergoing allogeneic hematopoietic cell transplantation (HCT).

SECONDARY AND EXPLORATORY OBJECTIVES:

I. Evaluate time to neutrophil and platelets engraftment.

II. Evaluate transplant-related mortality (TRM).

III. Evaluate disease free and overall survivals.

IV. Evaluate risk of graft versus host disease (GVHD)

V. Evaluate incidence of infectious complications.

VI. Assess the kinetics of engraftment and immune reconstitution.

OUTLINE:

CONDITIONING REGIMEN: All patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6, fludarabine IV over 30 minutes on days -6 to -2, thiotepa IV over 2 hours on days -5 and -4, and total body irradiation (TBI) on days -2 and -1.

UMBILICAL CORD BLOOD (UCB) INFUSION: There would be 2 consecutive cohorts. First 5-7 patients will be assigned to cohort I. Upon successful enrollment of the first cohort patients will be assigned to cohort II.

COHORT I: Patients receive a unit of valproic acid-expanded UCB-derived CD34-positive cells, a unit of the T-cell containing portion of the expanded UCB, and a unit of UCB that has not been manipulated, all via infusion. All UCB unit infusions occur on day 0 and are separated by at least 2 hours.

COHORT II: Patients receive a unit of valproic acid-expanded UCB-derived CD34-positive cells and a unit of the T-cell containing portion of the expanded UCB as in Cohort I. Both parts of UCB unit infusions occur on day 0 and are separated by at least 2 hours.

GVHD PROPHYLAXIS: All patients receive tacrolimus IV continuously every 24 hours or orally (PO) on days -3 to 120 and mycophenolate mofetil IV or PO three times daily (TID) on days 0-60.

After completion of study treatment, patients are followed up to 1 year.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Icahn School of Medicine at Mount Sinai

Principal Investigator
Alla Keyzner

Trial IDs

Primary ID 18-2534
Secondary IDs NCI-2019-00600
Clinicaltrials.gov ID NCT03885947