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Infusion of Expanded Cord Blood Cells in Addition to Single Cord Blood Transplant in Treating Patients With Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT03399773
Recruitment Status : Withdrawn (Development halted in HSCT.)
First Posted : January 16, 2018
Last Update Posted : March 13, 2019
Sponsor:
Collaborators:
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Nohla Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE December 15, 2017
First Posted Date  ICMJE January 16, 2018
Last Update Posted Date March 13, 2019
Actual Study Start Date  ICMJE August 15, 2018
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
Incidence of graft failure [ Time Frame: Up to 45 days post-transplant ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Graft failure [ Time Frame: 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 BM)
  • Incidence and severity of acute graft versus host disease [ Time Frame: 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)
  • Incidence and severity of chronic graft versus host disease (GVHD) [ Time Frame: 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)
Change History Complete list of historical versions of study NCT03399773 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • Incidence of CTCAE Grade >=3 Adverse Events within the first 24 hours after infusion [ Time Frame: Up to 100 days post-transplant ]
  • Time to neutrophil engraftment [ Time Frame: Up to 45 days post-transplant ]
  • Time to platelet engraftment [ Time Frame: Up to 100 days post-transplant ]
  • Incidence of severe acute graft-versus-host disease (GVHD) [ Time Frame: Up to 100 days post-transplant ]
  • Incidence of chronic graft-versus-host disease (GVHD) [ Time Frame: Up to 2-years post-transplant ]
  • Incidence of non-relapse mortality [ Time Frame: Up to 1-year post-transplant ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Neutrophil engraftment [ Time Frame: 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-CBT nadir.
  • Platelet engraftment measured by the number of participants with a platelet count > 20,000/μl without subsequent transfusions for 7 days. [ Time Frame: Up to day 100 post-transplant ]
  • Adverse events [ Time Frame: Up to day 100 post-transplant ]
    Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
  • Non-relapse mortality [ Time Frame: At day 100 post-transplant ]
  • Non-relapse mortality [ Time Frame: At one year post-transplant ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Infusion of Expanded Cord Blood Cells in Addition to Single Cord Blood Transplant in Treating Patients With Hematologic Malignancies
Official Title  ICMJE Infusion of Off the Shelf Ex Vivo Expanded Cryopreserved Progenitor Cells (NLA101) in the Setting of Single Cord Blood Transplantation for Patients With Hematologic Malignancies
Brief Summary This phase II trial studies the effect of ex vivo expanded cord blood progenitor cells (NLA101) on outcomes from single cord blood transplant for hematologic malignancies. 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. NLA101 is intended to support neutrophil engraftment and reduce GVHD following transplant.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Biphenotypic Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Myelogenous Leukemia
  • Myelodysplastic Syndromes
Intervention  ICMJE
  • Biological: Ex-Vivo Expanded Cord Blood Progenitor Cell Infusion
    Given IV
    Other Names:
    • NLA101
    • Dilanubicel
  • Drug: Cyclophosphamide
    Given IV
  • Drug: Fludarabine
    Given IV
  • Drug: Thiotepa
    Given IV
  • Radiation: Total-Body Irradiation
    Undergo TBI
  • Procedure: Umbilical Cord Blood Transplantation
    Given IV
Study Arms  ICMJE Experimental: Treatment (chemotherapy, TBI, NLA101)

Patients receive either regimen A (High Dose TBI) or regimen B (Intermediate Dose).

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 NLA101 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, thiotepa IV over 4 hours on days -5 and -4, and TBI on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by NLA101 IV within the next 24 hours on day 0.

Interventions:
  • Biological: Ex-Vivo Expanded Cord Blood Progenitor Cell Infusion
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
  • Drug: Thiotepa
  • Radiation: Total-Body Irradiation
  • Procedure: Umbilical Cord Blood Transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: March 11, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2018)
15
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Criteria:

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)
    • Myelodysplasia (MDS)
    • Chronic Myeloid Leukemia (CML)
  • High dose TBI regimen: 18 to =< 45 years
  • Intermediate intensity regimen: 18 to =< 65 years
  • Karnofsky >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1 (and non-age adjusted CI <=5 if >45 years)
  • Adequate renal, hepatic, pulmonary, and cardiac function
  • Ability to understand and the willingness to sign a written informed consent form

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) consultant
  • History of human immunodeficiency virus (HIV) infection
  • Pregnant or breastfeeding
  • Prior allogeneic transplant
  • Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03399773
Other Study ID Numbers  ICMJE 9910
NCI-2017-02205 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9910 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
P50HL110787 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nohla Therapeutics, Inc.
Study Sponsor  ICMJE Nohla Therapeutics, Inc.
Collaborators  ICMJE
  • Fred Hutchinson Cancer Research Center
  • National Cancer Institute (NCI)
  • National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE
Principal Investigator: Filippo Milano Fred Hutch/University of Washington Cancer Consortium
PRS Account Nohla Therapeutics, Inc.
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP