Infusion of Expanded Cord Blood Cells in Addition to Single Cord Blood Transplant in Treating Patients With Acute Leukemia, Chronic Myeloid Leukemia, or Myelodysplastic Syndromes

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT03399773
Collaborator
Nohla Therapeutics, Inc. (Industry), National Cancer Institute (NCI) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
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Study Details

Study Description

Brief Summary

This phase II trial studies how well donor umbilical cord blood transplant with ex-vivo expanded cord blood progenitor cells (dilanubicel) works in treating patients with blood cancer. Before the transplant, patients will receive chemotherapy (fludarabine, cyclophosphamide and in some cases thiotepa) and radiation therapy. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

OUTLINE:

Patients receive either regimen A or regimen B.

REGIMEN A: Patients (18 through 45 years old) receive fludarabine intravenously (IV) over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo total body irradiation (TBI) twice daily (BID) on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.

REGIMEN B: Patients (18 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI once daily (QD) on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.

After completion of study treatment, patients are followed up at 180 days, 1 year, and 2 years.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Pilot Study: Infusion of Off-the-Shelf Ex Vivo Expanded Cryopreserved Progenitor Cells (Dilanubicel) in the Setting of Single Cord Blood Transplantation for Patients With Hematologic Malignancies
Actual Study Start Date :
May 10, 2022
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Jun 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (chemotherapy, TBI, NLA101)

Patients receive either regimen A or regimen B. REGIMEN A: Patients (18 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0. REGIMEN B: Patients (18 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0.

Biological: Dilanubicel
Given IV
Other Names:
  • Allogeneic UCB-derived Hematopoietic Stem and Progenitor Cells NLA101
  • NLA101
  • Allogeneic Umbilical Cord Blood-derived HSPCs NLA101
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
  • Carloxan
  • Cicloxal
  • Mitoxan
  • Neosar
  • Revimmune
  • Drug: Fludarabine
    Given IV
    Other Names:
  • fluoroadenine
  • Fluradosa
  • Drug: Thiotepa
    Given IV
    Other Names:
  • Oncotiotepa
  • STEPA
  • Tepadina
  • TESPA
  • Tespamine
  • Thiofosfamide
  • Thiofozil
  • Thiophosphoramide
  • Thiotef
  • Triethylene Thiophosphoramide
  • Radiation: Total-Body Irradiation
    Undergo TBI
    Other Names:
  • SCT_TBI
  • Total Body Irradiation
  • Whole Body Irradiation
  • Whole-Body Irradiation
  • Procedure: Umbilical Cord Blood Transplantation
    Given IV
    Other Names:
  • Cord Blood Transplantation
  • UCB transplantation
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of graft failure [Up to day 45 post-transplant]

      Primary graft failure/rejection as defined by no neutrophil recovery (regardless of donor chimerism) or autologous recovery (neutrophil recovery but < 10% donor chimerism in blood and bone marrow [BM]).

    2. Incidence and severity of acute graft versus host disease (GVHD) [At day 100 post-transplant]

      Assessed using the Acute GVHD Grading Scale (reference: Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825-8).

    3. Incidence and severity of chronic graft versus host disease (GVHD) [Up to approximately 2 years post-transplant]

      Assessed using the Chronic GVHD Grading Scale (reference: Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. I. Diagnosis and Staging Working Group report. Blood Marrow Transplant 2005; 11: 945-56).

    Secondary Outcome Measures

    1. Time to neutrophil engraftment [Up to day 45 post-transplant]

      The day of neutrophil recovery will be the 1st day of 2 consecutive days of absolute neutrophil count at or above 500 after the 1st post-cord blood transplant nadir.

    2. Time to platelet engraftment [Up to day 100 post-transplant]

      Measured by the number of participants with a platelet count > 20,000/ul without subsequent transfusions for 7 days

    3. Incidence of adverse events [Up to day 100 post-transplant]

      Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.

    4. Incidence of non-relapse mortality [At day 100 post-transplant]

    5. Incidence of non-relapse mortality [At 1 year post-transplant]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patient must have hematologic malignancy that meets institutional eligibility requirements for cord blood transplant

    • Malignancies included are:

    • Acute leukemia, including acute myeloid leukemia (AML), biphenotypic acute leukemia or mixed-lineage leukemia, acute lymphoblastic leukemia (ALL); all patients must be in complete response (CR) as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with adequate cellularity to assess remission status

    • Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% in a representative bone marrow aspirate

    • Chronic myeloid leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase inhibitor therapy

    • High dose TBI regimen: 18 to =< 45 years

    • Intermediate intensity regimen: 18 to =< 65 years

    • Patients 18 to =< 45 years: Karnofsky (>= 18 years old) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1

    • Patients > 45 to =< 65 years: Karnofsky >= 70 or ECOG 0-1 and non-age adjusted comorbidity index =< 5

    • Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL

    • Total serum bilirubin must be < 3 mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis

    • Transaminases must be < 3 x the upper limit of normal per reference values of treating institution

    • Carbon monoxide diffusing capability (DLCO) corrected >= 60% normal (may not be on supplemental oxygen)

    • Left ventricular ejection fraction >= 50% OR

    • Shortening fraction > 26%

    • Ability to understand and the willingness to sign a written informed consent form

    • DONOR: Minimum requirement: The cord blood (CB) unit must be matched at a minimum at 4/6 HLA-A, B antigens and DRB1 allele with the recipient; therefore, 0-2 mismatches at the A or B or DRB1 loci based on intermediate resolution at HLA-A, B and high resolution allele level typing at HLA- DRB1 are allowed

    • DONOR: Institutional guidelines for HLA-match may be followed as long as the minimum criteria for HLA-matching as above are met

    • DONOR: The CB unit selected for transplant must have a MINIMUM of 2.5 x 10^7 TNC/kg

    • DONOR: The minimum recommended CD34/kg cell dose is 1.7 x 10^5 CD34/kg

    • DONOR: A domestic backup unit, meeting the same HLA and cell dose requirements, must be identified and reserved prior to the start of the treatment plan for possible infusion in the unlikely event of poor post-thaw viability of the primary CB unit

    Exclusion Criteria:
    • Uncontrolled viral or bacterial infection at the time of study enrollment

    • Active or recent (prior 6 month) invasive fungal infection unless cleared by infectious disease (ID) consult

    • History of human immunodeficiency virus (HIV) infection

    • Pregnant or breastfeeding

    • Prior allogeneic transplant

    • Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy; diagnostic lumbar puncture is to be performed

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fred Hutch/University of Washington Cancer Consortium Seattle Washington United States 98109

    Sponsors and Collaborators

    • Fred Hutchinson Cancer Center
    • Nohla Therapeutics, Inc.
    • National Cancer Institute (NCI)
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Filippo Milano, Fred Hutch/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT03399773
    Other Study ID Numbers:
    • 9910
    • NCI-2017-02205
    • 9910
    • P30CA015704
    • P50HL110787
    • RG9218003
    First Posted:
    Jan 16, 2018
    Last Update Posted:
    May 18, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 18, 2022