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Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

Sponsor
Nohla Therapeutics, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01690520
Collaborator
National Cancer Institute (NCI) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
163
Enrollment
8
Locations
2
Arms
89.6
Actual Duration (Months)
20.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well donor umbilical cord blood transplant with or without ex-vivo expanded cord blood progenitor cells works in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy stem cells and ex-vivo expanded cord blood progenitor cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether giving donor umbilical cord blood transplant plus ex-vivo expanded cord blood progenitor cells is more effective than giving a donor umbilical cord blood transplant alone.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. Compare the time to neutrophil engraftment (absolute neutrophil count [ANC] >= 500) in patients receiving a standard of care myeloablative cord blood transplant (CBT) augmented with an off-the-shelf pre-expanded and cryopreserved cord blood product to those who do not receive the product.
SECONDARY OBJECTIVES:

  1. Provide initial data on clinical and economic benefit, such as time to platelet engraftment, duration of initial hospitalization, transplant-related mortality (TRM), death without engraftment, and incidence of severe infections in the first 100 days post-transplant.

  2. The kinetics of immune system recovery will also be evaluated in both arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Standard of Care Arm:

CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose total-body irradiation (TBI) twice daily (BID) on days -4 to -1 OR, patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI once daily (QD) on days -2 to -1.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated umbilical cord blood (UCB) transplant on day 0.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or thrice daily (TID) (children) or orally (PO) on days -3 to 100 with taper beginning on day 101. Patients also receive mycophenolate mofetil (MMF) IV TID on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin taper if there is no evidence of GVHD and are well-engrafted from one donor unit.

Experimental Arm:

CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also receive an infusion of ex vivo-expanded cord blood progenitors at least 4 hours after completion of UCB transplant.

GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.

After completion of study treatment, patients are followed up periodically for 2 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
163 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Multi-Center, Open-Label Randomized Study of Single or Double Myeloablative Cord Blood Transplantation With or Without Infusion of Off-The-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells in Patients With Hematologic Malignancies
Actual Study Start Date :
Dec 11, 2012
Actual Primary Completion Date :
Sep 18, 2018
Actual Study Completion Date :
May 29, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm I (standard of care)

CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.

Drug: Cyclophosphamide
Given IV

Drug: Cyclosporine
Given IV or PO

Drug: Fludarabine Phosphate
Given IV

Drug: Mycophenolate Mofetil
Given IV or PO

Drug: Thiotepa
Given IV

Radiation: Total-Body Irradiation
Undergo high dose or middle intensity TBI

Procedure: Umbilical Cord Blood Transplantation
Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation

    		•
    Experimental: Arm II (experimental)

    CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.

    Drug: Cyclophosphamide
    Given IV

    Drug: Cyclosporine
    Given IV or PO

    Biological: Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion
    Given IV
    Other Names:
  • NLA101
  • Dilanubicel

    • Drug: Fludarabine Phosphate
    Given IV

    Drug: Mycophenolate Mofetil
    Given IV or PO

    Drug: Thiotepa
    Given IV

    Radiation: Total-Body Irradiation
    Undergo high dose or middle intensity TBI

    Procedure: Umbilical Cord Blood Transplantation
    Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
    Other Names:
  • Cord Blood Transplantation
  • UCB transplantation

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Time to Neutrophil Engraftment [Up to 55 days post-transplant]

      First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.

    Secondary Outcome Measures

    1. Time to Platelet Engraftment (20k) [Up to 100 days post-transplant]

      First day of seven consecutive days with platelet count equal to or greater than 20,000 cells/microliter without platelet transfusions measured from day of transplant.

    2. Overall Survival [Up to 2 years]

    3. Non-relapse Mortality [Up to 2 years]

    4. Proportion of Patients With Severe Acute Graft Versus Host Disease [Up to 100 days post-transplant]

    5. Proportion of Participants With Chronic Graft Versus Host Disease [Up to 2 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Months to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Age criteria:

    • High dose TBI regimen: 6 months to =< 45 years

    • Middle intensity TBI regimen: 6 months to =< 65 years

    • Conditioning regimen selection should be based on the underlying disease, presence of minimal residual disease (MRD), age, co-morbidities, attending physician, and site preference; conditioning regimen will not require stratification of the randomization due to heterogeneity in the cohort of eligible patients.

    • Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia

    • All patients must have acute myeloid leukemia (AML) that is considered best treated by stem cell transplant by the referring physician and the attending transplant physician

    • All patients must be in complete remission (CR) as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity

    = 15% for age

    • Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator prior to enrollment

    • Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia

    • High risk first complete remission (CR1) (for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia [MLL] rearrangements, hypodiploid); or high risk (HR) as defined by referring institution treatment protocol greater than 1 cycle to obtain CR; second complete remission (CR2) or greater

    • All patients must be in CR as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age

    • Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator prior to enrollment

    • Chronic myelogenous 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

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

    • Karnofsky (>= 16 years old) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1

    • Lansky (< 16 years old) >= 60

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

    • Children (< 18 years old): calculated creatinine clearance must be > 60 mL/min

    • 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 referring institution

    • Diffusing capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal

    • For pediatric patients unable to perform pulmonary function tests, oxygen (O2) saturation > 92% on room air

    • May not be on supplemental oxygen

    • Left ventricular ejection fraction > 45% OR

    • Shortening fraction > 26%

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

    Exclusion Criteria:

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

    • Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval

    • History of human immunodeficiency virus (HIV) infection

    • Pregnant or breastfeeding

    • Prior myeloablative transplant containing full dose TBI (greater than 8 Gy)

    • Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning; diagnostic lumbar puncture is to be performed per protocol

    • Patients >= 45 years: comorbidity score of 5 or higher

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    2 Stanford Cancer Institute Palo Alto Palo Alto California United States 94304
    3 University of Colorado Denver Colorado United States 80217-3364
    4 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    5 Mount Sinai Hospital New York New York United States 10029
    6 Duke University Medical Center Durham North Carolina United States 27710
    7 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    8 Fred Hutch/University of Washington Cancer Consortium Seattle Washington United States 98109

    Sponsors and Collaborators

    • 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)

    More Information

    Publications

    None provided.
    Responsible Party:
    Nohla Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT01690520
    Other Study ID Numbers:
    • 2603.00
    • NCI-2012-01572
    • 2603
    • 2603.00
    • P30CA015704
    • P50HL110787
    First Posted:
    Sep 21, 2012
    Last Update Posted:
    Jul 6, 2021
    Last Verified:
    Jun 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Preleukemia
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Leukemia, Biphenotypic, Acute
    Myelodysplastic Syndromes
    Syndrome
    Cyclosporine
    Mycophenolic Acid
    Cyclophosphamide
    Thiotepa
    Fludarabine
    Fludarabine phosphate
    Cyclosporins

    Study Results

    Participant Flow

    Recruitment Details The Full Analysis Set includes all randomized subjects (78 in Arm I SOC and 82 in Arm II Expanded Arm). The modified intent to treat (mITT) analysis set requires subjects in the FAS to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug and are therefore not included in the mITT analysis set (78 in SOC and 80 in Expanded Arm).
    Pre-assignment Detail
    Arm/Group Title Arm I (Standard of Care) Arm II (Experimental)
    Arm/Group Description CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
    Period Title: Overall Study
    STARTED 78 82
    Modified Intent to Treat (mITT) 78 80
    COMPLETED 27 35
    NOT COMPLETED 51 47

    Baseline Characteristics

    Arm/Group Title Arm I (Standard of Care) Arm II (Experimental) Total
    Arm/Group Description CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant Total of all reporting groups
    Overall Participants 78 82 160
    Age (Count of Participants)
    <=18 years
    27
    34.6%
    24
    29.3%
    51
    31.9%
    Between 18 and 65 years
    51
    65.4%
    58
    70.7%
    109
    68.1%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    26.76
    (14.858)
    27.72
    (14.699)
    27.25
    (14.738)
    Sex: Female, Male (Count of Participants)
    Female
    27
    34.6%
    40
    48.8%
    67
    41.9%
    Male
    51
    65.4%
    42
    51.2%
    93
    58.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    19
    24.4%
    18
    22%
    37
    23.1%
    Not Hispanic or Latino
    59
    75.6%
    57
    69.5%
    116
    72.5%
    Unknown or Not Reported
    0
    0%
    7
    8.5%
    7
    4.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    1.3%
    0
    0%
    1
    0.6%
    Asian
    15
    19.2%
    10
    12.2%
    25
    15.6%
    Native Hawaiian or Other Pacific Islander
    3
    3.8%
    0
    0%
    3
    1.9%
    Black or African American
    6
    7.7%
    4
    4.9%
    10
    6.3%
    White
    34
    43.6%
    52
    63.4%
    86
    53.8%
    More than one race
    7
    9%
    9
    11%
    16
    10%
    Unknown or Not Reported
    12
    15.4%
    7
    8.5%
    19
    11.9%
    Region of Enrollment (participants) [Number]
    United States
    78
    100%
    82
    100%
    160
    100%
    Height (cm) (centimeters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [centimeters]
    160.09
    (23.481)
    159.85
    (24.680)
    159.97
    (24.028)
    Weight (kg) (kilograms) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms]
    67.70
    (26.886)
    69.77
    (27.103)
    68.76
    (26.933)
    Cord Blood Units Received (Count of Participants)
    1 Cord Blood Unit
    22
    28.2%
    17
    20.7%
    39
    24.4%
    2 Cord Blood Units
    56
    71.8%
    65
    79.3%
    121
    75.6%

    Outcome Measures

    1. Primary Outcome
    Title Time to Neutrophil Engraftment
    Description First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.
    Time Frame Up to 55 days post-transplant

    Outcome Measure Data

    Analysis Population Description
    The primary analysis set for the analysis of Neutrophil Enrgraftment and Platelet Engraftment was the modified intent to treat (mITT) analysis set. The difference between the full analysis set (FAS) and the mITT is the requirement to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug, and are therefore not included in the mITT analysis set, nor the primary efficacy analyses.
    Arm/Group Title Arm I (Standard of Care) Arm II (Experimental)
    Arm/Group Description CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
    Measure Participants 72 75
    Median (95% Confidence Interval) [days]
    20.0
    22.0
    2. Secondary Outcome
    Title Time to Platelet Engraftment (20k)
    Description First day of seven consecutive days with platelet count equal to or greater than 20,000 cells/microliter without platelet transfusions measured from day of transplant.
    Time Frame Up to 100 days post-transplant

    Outcome Measure Data

    Analysis Population Description
    The primary analysis set for the analysis of Neutrophil Enrgraftment and Platelet Engraftment was the modified intent to treat (mITT) analysis set. The difference between the full analysis set (FAS) and the mITT is the requirement to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug, and are therefore not included in the mITT analysis set, nor the primary efficacy analyses.
    Arm/Group Title Arm I (Standard of Care) Arm II (Experimental)
    Arm/Group Description CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
    Measure Participants 65 66
    Median (95% Confidence Interval) [days]
    40.0
    38.0
    3. Secondary Outcome
    Title Overall Survival
    Description
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Standard of Care) Arm II (Experimental)
    Arm/Group Description CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
    Measure Participants 78 80
    Count of Participants [Participants]
    52
    66.7%
    57
    69.5%
    4. Secondary Outcome
    Title Non-relapse Mortality
    Description
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Standard of Care) Arm II (Experimental)
    Arm/Group Description CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
    Measure Participants 78 80
    Count of Participants [Participants]
    16
    20.5%
    16
    19.5%
    5. Secondary Outcome
    Title Proportion of Patients With Severe Acute Graft Versus Host Disease
    Description
    Time Frame Up to 100 days post-transplant

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Standard of Care) Arm II (Experimental)
    Arm/Group Description CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
    Measure Participants 78 80
    Number (95% Confidence Interval) [proportion of participants]
    0.14
    0.2%
    0.16
    0.2%
    6. Secondary Outcome
    Title Proportion of Participants With Chronic Graft Versus Host Disease
    Description
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm I (Standard of Care) Arm II (Experimental)
    Arm/Group Description CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
    Measure Participants 78 80
    Count of Participants [Participants]
    27
    34.6%
    23
    28%

    Adverse Events

    Time Frame 84 days
    Adverse Event Reporting Description
    Arm/Group Title Arm I (Standard of Care) Arm II (Experimental)
    Arm/Group Description CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV Fludarabine Phosphate: Given IV Mycophenolate Mofetil: Given IV or PO Thiotepa: Given IV Total-Body Irradiation: Undergo high dose or middle intensity TBI Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
    All Cause Mortality
    Arm I (Standard of Care) Arm II (Experimental)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/78 (32.1%) 21/82 (25.6%)
    Serious Adverse Events
    Arm I (Standard of Care) Arm II (Experimental)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 48/78 (61.5%) 55/82 (67.1%)
    Blood and lymphatic system disorders
    Disseminated intravascular coagulation 0/78 (0%) 1/82 (1.2%)
    Lymphatic disorder 0/78 (0%) 1/82 (1.2%)
    Febrile neutropenia 1/78 (1.3%) 1/82 (1.2%)
    Cardiac disorders
    Atrial flutter 0/78 (0%) 1/82 (1.2%)
    Cardiac arrest 0/78 (0%) 1/82 (1.2%)
    Cardiac failure 0/78 (0%) 1/82 (1.2%)
    Pericardial effusion 0/78 (0%) 1/82 (1.2%)
    Sinus bradycardia 0/78 (0%) 1/82 (1.2%)
    Tachycardia 1/78 (1.3%) 0/82 (0%)
    Gastrointestinal disorders
    Abdominal pain 2/78 (2.6%) 1/82 (1.2%)
    Jejunal perforation 0/78 (0%) 1/82 (1.2%)
    Lower gastrointestinal haemorrhage 1/78 (1.3%) 0/82 (0%)
    Pancreatitis 0/78 (0%) 1/82 (1.2%)
    Pneumatosis intestinalis 0/78 (0%) 1/82 (1.2%)
    Diarrhoea 1/78 (1.3%) 6/82 (7.3%)
    Colitis 1/78 (1.3%) 1/82 (1.2%)
    Nausea 3/78 (3.8%) 2/82 (2.4%)
    Vomiting 2/78 (2.6%) 3/82 (3.7%)
    General disorders
    Pyrexia 14/78 (17.9%) 17/82 (20.7%)
    Multiple organ dysfunction syndrome 1/78 (1.3%) 2/82 (2.4%)
    Chest pain 1/78 (1.3%) 0/82 (0%)
    Chills 0/78 (0%) 1/82 (1.2%)
    Complication associated with device 1/78 (1.3%) 0/82 (0%)
    Death 0/78 (0%) 1/82 (1.2%)
    Non-cardiac chest pain 1/78 (1.3%) 0/82 (0%)
    Hepatobiliary disorders
    Hepatic failure 1/78 (1.3%) 0/82 (0%)
    Immune system disorders
    Acute graft versus host disease in intestine 1/78 (1.3%) 2/82 (2.4%)
    Graft versus host disease in gastrointestinal tract 2/78 (2.6%) 1/82 (1.2%)
    Hypersensitivity 1/78 (1.3%) 0/82 (0%)
    Acute graft versus host disease in liver 1/78 (1.3%) 1/82 (1.2%)
    Graft versus host disease 5/78 (6.4%) 7/82 (8.5%)
    Infections and infestations
    Clostridium difficile infection 0/78 (0%) 1/82 (1.2%)
    Cytomegalovirus gastritis 0/78 (0%) 1/82 (1.2%)
    Cytomegalovirus infection 1/78 (1.3%) 0/82 (0%)
    Eye infection 0/78 (0%) 1/82 (1.2%)
    Herpes virus infection 0/78 (0%) 1/82 (1.2%)
    Klebsiella infection 0/78 (0%) 1/82 (1.2%)
    Oral infection 0/78 (0%) 1/82 (1.2%)
    Pneumonia klebsiella 1/78 (1.3%) 0/82 (0%)
    Pseudomonas infection 1/78 (1.3%) 0/82 (0%)
    Rhinovirus infection 1/78 (1.3%) 0/82 (0%)
    Sinusitis 1/78 (1.3%) 0/82 (0%)
    Skin infection 0/78 (0%) 1/82 (1.2%)
    Systemic candida 0/78 (0%) 1/82 (1.2%)
    Urinary tract infection 0/78 (0%) 1/82 (1.2%)
    Urinary tract infection enterococcal 1/78 (1.3%) 0/82 (0%)
    Sepsis 2/78 (2.6%) 5/82 (6.1%)
    Staphylococcal infection 2/78 (2.6%) 2/82 (2.4%)
    BK virus infection 1/78 (1.3%) 1/82 (1.2%)
    Cytomegalovirus viraemia 0/78 (0%) 2/82 (2.4%)
    Lung infection 2/78 (2.6%) 0/82 (0%)
    Pneumonia fungal 1/78 (1.3%) 1/82 (1.2%)
    Staphylococcal bacteraemia 0/78 (0%) 2/82 (2.4%)
    Injury, poisoning and procedural complications
    Infusion related reaction 0/78 (0%) 3/82 (3.7%)
    Transplant failure 1/78 (1.3%) 2/82 (2.4%)
    Subdural haematoma 0/78 (0%) 1/82 (1.2%)
    Investigations
    Alanine aminotransferase increased 0/78 (0%) 1/82 (1.2%)
    Aspartate aminotransferase increased 0/78 (0%) 1/82 (1.2%)
    Blood bilirubin increased 0/78 (0%) 1/82 (1.2%)
    Platelet count decreased 0/78 (0%) 1/82 (1.2%)
    Metabolism and nutrition disorders
    Hyperuricaemia 1/78 (1.3%) 0/82 (0%)
    Hypokalemia 1/78 (1.3%) 0/82 (0%)
    Hypophosphataemia 1/78 (1.3%) 0/82 (0%)
    Nervous system disorders
    Encephalopathy 0/78 (0%) 1/82 (1.2%)
    Haemorrhage intracranial 1/78 (1.3%) 0/82 (0%)
    Headache 0/78 (0%) 1/82 (1.2%)
    Neuropathy peripheral 1/78 (1.3%) 0/82 (0%)
    Posterior reversible encephalopathy syndrome 1/78 (1.3%) 0/82 (0%)
    Seizure 2/78 (2.6%) 0/82 (0%)
    Psychiatric disorders
    Delirium 1/78 (1.3%) 0/82 (0%)
    Renal and urinary disorders
    Haematuria 1/78 (1.3%) 0/82 (0%)
    Acute kidney injury 4/78 (5.1%) 4/82 (4.9%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 1/78 (1.3%) 2/82 (2.4%)
    Acute respiratory distress syndrome 0/78 (0%) 1/82 (1.2%)
    Cough 1/78 (1.3%) 0/82 (0%)
    Dyspnoea 1/78 (1.3%) 0/82 (0%)
    Organising pneumonia 1/78 (1.3%) 0/82 (0%)
    Pleural effusion 1/78 (1.3%) 0/82 (0%)
    Pulmonary alveolar haemorrhage 1/78 (1.3%) 0/82 (0%)
    Pulmonary infarction 0/78 (0%) 1/82 (1.2%)
    Pulmonary mass 0/78 (0%) 1/82 (1.2%)
    Pulmonary oedema 0/78 (0%) 1/82 (1.2%)
    Hypoxia 4/78 (5.1%) 3/82 (3.7%)
    Respiratory failure 4/78 (5.1%) 7/82 (8.5%)
    Skin and subcutaneous tissue disorders
    Skin ulcer 0/78 (0%) 1/82 (1.2%)
    Vascular disorders
    Hypertension 0/78 (0%) 1/82 (1.2%)
    Hypotension 4/78 (5.1%) 3/82 (3.7%)
    Other (Not Including Serious) Adverse Events
    Arm I (Standard of Care) Arm II (Experimental)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 71/78 (91%) 73/82 (89%)
    Blood and lymphatic system disorders
    Haemolytic uraemic syndrome 3/78 (3.8%) 3/82 (3.7%)
    Febrile neutropenia 1/78 (1.3%) 1/82 (1.2%)
    Thrombotic microangiopathy 1/78 (1.3%) 0/82 (0%)
    Thrombotic thrombocytopenic purpura 0/78 (0%) 1/82 (1.2%)
    Haemolysis 2/78 (2.6%) 1/82 (1.2%)
    Anaemia 5/78 (6.4%) 2/82 (2.4%)
    Cardiac disorders
    Pericardial effusion 2/78 (2.6%) 2/82 (2.4%)
    Cardiac failure 1/78 (1.3%) 1/82 (1.2%)
    Bradycardia 1/78 (1.3%) 0/82 (0%)
    Myocardial infarction 0/78 (0%) 1/82 (1.2%)
    Tachycardia 1/78 (1.3%) 0/82 (0%)
    Endocrine disorders
    Adrenal insufficiency 1/78 (1.3%) 1/82 (1.2%)
    Gastrointestinal disorders
    Colitis 7/78 (9%) 9/82 (11%)
    Enterocolitis 2/78 (2.6%) 0/82 (0%)
    Gastritis 1/78 (1.3%) 1/82 (1.2%)
    Gastrointestinal pain 1/78 (1.3%) 1/82 (1.2%)
    Ileus 2/78 (2.6%) 0/82 (0%)
    Large intestinal haemorrhage 1/78 (1.3%) 1/82 (1.2%)
    Gastrointestinal haemorrhage 1/78 (1.3%) 0/82 (0%)
    Impaired gastric emptying 0/78 (0%) 1/82 (1.2%)
    Lower gastrointestinal haemorrhage 1/78 (1.3%) 0/82 (0%)
    Oesophagitis 1/78 (1.3%) 0/82 (0%)
    Periodontal disease 1/78 (1.3%) 0/82 (0%)
    Proctitis 0/78 (0%) 1/82 (1.2%)
    Stomatitis 30/78 (38.5%) 36/82 (43.9%)
    Nausea 15/78 (19.2%) 25/82 (30.5%)
    Diarrhoea 11/78 (14.1%) 11/82 (13.4%)
    Vomiting 5/78 (6.4%) 9/82 (11%)
    Abdominal pain 8/78 (10.3%) 4/82 (4.9%)
    Pain 8/78 (10.3%) 3/82 (3.7%)
    Pyrexia 1/78 (1.3%) 2/82 (2.4%)
    General disorders
    Fatigue 3/78 (3.8%) 1/82 (1.2%)
    Oedema peripheral 0/78 (0%) 2/82 (2.4%)
    Chills 0/78 (0%) 1/82 (1.2%)
    Mucosal inflammation 0/78 (0%) 1/82 (1.2%)
    Multiple organ dysfunction syndrome 1/78 (1.3%) 0/82 (0%)
    Pneumatosis 1/78 (1.3%) 0/82 (0%)
    Immune system disorders
    Anaphylactic reaction 1/78 (1.3%) 0/82 (0%)
    Graft versus host disease 0/78 (0%) 1/82 (1.2%)
    Infections and infestations
    Enterococcal infection 5/78 (6.4%) 3/82 (3.7%)
    Adenovirus infection 4/78 (5.1%) 2/82 (2.4%)
    Alpha haemolytic streptococcal infection 5/78 (6.4%) 1/82 (1.2%)
    Cystitis 4/78 (5.1%) 2/82 (2.4%)
    Urinary tract infection 3/78 (3.8%) 3/82 (3.7%)
    BK virus infection 1/78 (1.3%) 3/82 (3.7%)
    Device related infection 2/78 (2.6%) 2/82 (2.4%)
    Sinusitis 2/78 (2.6%) 2/82 (2.4%)
    Skin infection 1/78 (1.3%) 3/82 (3.7%)
    Candida infection 2/78 (2.6%) 0/82 (0%)
    Encephalitis 0/78 (0%) 2/82 (2.4%)
    Escherichia infection 1/78 (1.3%) 1/82 (1.2%)
    Human polyomavirus infection 2/78 (2.6%) 0/82 (0%)
    Pseudomonas infection 1/78 (1.3%) 1/82 (1.2%)
    Sepsis 1/78 (1.3%) 1/82 (1.2%)
    Stomatococcal infection 1/78 (1.3%) 1/82 (1.2%)
    Upper respiratory tract infection 2/78 (2.6%) 0/82 (0%)
    Actinomycotic sepsis 1/78 (1.3%) 0/82 (0%)
    Administration site cellulitis 1/78 (1.3%) 0/82 (0%)
    Bacillus infection 1/78 (1.3%) 0/82 (0%)
    Bacteraemia 1/78 (1.3%) 0/82 (0%)
    Coronavirus infection 1/78 (1.3%) 0/82 (0%)
    Corynebacterium infection 1/78 (1.3%) 0/82 (0%)
    Cytomegalovirus colitis 1/78 (1.3%) 0/82 (0%)
    Enterobacter infection 1/78 (1.3%) 0/82 (0%)
    Enterocolitis infection 1/78 (1.3%) 0/82 (0%)
    Escherichia bacteraemia 0/78 (0%) 1/82 (1.2%)
    Fusobacterium infection 0/78 (0%) 1/82 (1.2%)
    Gastric infection 1/78 (1.3%) 0/82 (0%)
    Influenza 1/78 (1.3%) 0/82 (0%)
    Leuconostoc infection 0/78 (0%) 1/82 (1.2%)
    Lip infection 0/78 (0%) 1/82 (1.2%)
    Osteomyelitis 1/78 (1.3%) 0/82 (0%)
    Wound infection 1/78 (1.3%) 0/82 (0%)
    Staphylococcal infection 7/78 (9%) 5/82 (6.1%)
    Lung infection 7/78 (9%) 6/82 (7.3%)
    Human herpesvirus 6 infection 6/78 (7.7%) 5/82 (6.1%)
    Cytomegalovirus infection 2/78 (2.6%) 7/82 (8.5%)
    Streptococcal infection 7/78 (9%) 2/82 (2.4%)
    Bacterial infection 4/78 (5.1%) 1/82 (1.2%)
    Clostridium difficile infection 3/78 (3.8%) 0/82 (0%)
    Injury, poisoning and procedural complications
    Infusion related reaction 0/78 (0%) 1/82 (1.2%)
    Post procedural haemorrhage 1/78 (1.3%) 0/82 (0%)
    Radiation skin injury 1/78 (1.3%) 0/82 (0%)
    Tracheal haemorrhage 1/78 (1.3%) 0/82 (0%)
    Investigations
    Blood bilirubin increased 11/78 (14.1%) 8/82 (9.8%)
    Alanine aminotransferase increased 3/78 (3.8%) 3/82 (3.7%)
    Aspartate aminotransferase increased 2/78 (2.6%) 2/82 (2.4%)
    Blood aluminium increased 1/78 (1.3%) 3/82 (3.7%)
    Blood alkaline phosphatase increased 1/78 (1.3%) 1/82 (1.2%)
    Weight decreased 2/78 (2.6%) 0/82 (0%)
    White blood cell count increased 0/78 (0%) 2/82 (2.4%)
    Electrocardiogram QT prolonged 1/78 (1.3%) 0/82 (0%)
    Urine output decreased 0/78 (0%) 1/82 (1.2%)
    Weight increased 1/78 (1.3%) 0/82 (0%)
    Platelet count decreased 13/78 (16.7%) 9/82 (11%)
    Neutrophil count decreased 8/78 (10.3%) 3/82 (3.7%)
    White blood cell count decreased 4/78 (5.1%) 1/82 (1.2%)
    Blood creatinine increased 1/78 (1.3%) 6/82 (7.3%)
    Metabolism and nutrition disorders
    Decreased appetite 39/78 (50%) 38/82 (46.3%)
    Hypokalemia 14/78 (17.9%) 14/82 (17.1%)
    Hyperglycaemia 8/78 (10.3%) 12/82 (14.6%)
    Hyponatraemia 9/78 (11.5%) 10/82 (12.2%)
    Hypophosphataemia 6/78 (7.7%) 10/82 (12.2%)
    Hypertriglyceridaemia 3/78 (3.8%) 5/82 (6.1%)
    Hyperkalaemia 3/78 (3.8%) 3/82 (3.7%)
    Hypocalcaemia 2/78 (2.6%) 2/82 (2.4%)
    Acidosis 1/78 (1.3%) 1/82 (1.2%)
    Hypermagnesaemia 1/78 (1.3%) 1/82 (1.2%)
    Hypernatraemia 1/78 (1.3%) 1/82 (1.2%)
    Iron overload 1/78 (1.3%) 1/82 (1.2%)
    Dehydration 1/78 (1.3%) 0/82 (0%)
    Hyperuricaemia 0/78 (0%) 1/82 (1.2%)
    Hypoalbuminaemia 0/78 (0%) 1/82 (1.2%)
    Hypomagnesaemia 1/78 (1.3%) 0/82 (0%)
    Musculoskeletal and connective tissue disorders
    Bone pain 1/78 (1.3%) 1/82 (1.2%)
    Back pain 1/78 (1.3%) 0/82 (0%)
    Muscular weakness 1/78 (1.3%) 0/82 (0%)
    Myalgia 1/78 (1.3%) 0/82 (0%)
    Pain in extremity 3/78 (3.8%) 0/82 (0%)
    Nervous system disorders
    Seizure 1/78 (1.3%) 1/82 (1.2%)
    Tremor 0/78 (0%) 2/82 (2.4%)
    Cognitive disorder 0/78 (0%) 1/82 (1.2%)
    Dysaesthesia 0/78 (0%) 1/82 (1.2%)
    Myoclonus 1/78 (1.3%) 0/82 (0%)
    Somnolence 1/78 (1.3%) 0/82 (0%)
    Headache 9/78 (11.5%) 5/82 (6.1%)
    Peripheral motor neuropathy 1/78 (1.3%) 2/82 (2.4%)
    Syncope 1/78 (1.3%) 2/82 (2.4%)
    Psychiatric disorders
    Depression 3/78 (3.8%) 1/82 (1.2%)
    Insomnia 1/78 (1.3%) 3/82 (3.7%)
    Anxiety 1/78 (1.3%) 1/82 (1.2%)
    Confusional state 1/78 (1.3%) 0/82 (0%)
    Delirium 1/78 (1.3%) 0/82 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/78 (1.3%) 3/82 (3.7%)
    Chronic kidney disease 0/78 (0%) 1/82 (1.2%)
    Urinary tract pain 1/78 (1.3%) 0/82 (0%)
    Haematuria 5/78 (6.4%) 4/82 (4.9%)
    Reproductive system and breast disorders
    Menorrhagia 0/78 (0%) 2/82 (2.4%)
    Vulvovaginal inflammation 1/78 (1.3%) 0/82 (0%)
    Vaginal haemorrhage 1/78 (1.3%) 2/82 (2.4%)
    Respiratory, thoracic and mediastinal disorders
    Pharyngeal inflammation 2/78 (2.6%) 0/82 (0%)
    Pneumonitis 1/78 (1.3%) 1/82 (1.2%)
    Acute respiratory distress syndrome 1/78 (1.3%) 0/82 (0%)
    Cough 1/78 (1.3%) 0/82 (0%)
    Organising pneumonia 1/78 (1.3%) 0/82 (0%)
    Pleural effusion 1/78 (1.3%) 0/82 (0%)
    Pneumothorax 0/78 (0%) 1/82 (1.2%)
    Pulmonary oedema 1/78 (1.3%) 0/82 (0%)
    Stridor 0/78 (0%) 1/82 (1.2%)
    Epistaxis 6/78 (7.7%) 6/82 (7.3%)
    Dyspnoea 1/78 (1.3%) 2/82 (2.4%)
    Hypoxia 8/78 (10.3%) 9/82 (11%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 37/78 (47.4%) 40/82 (48.8%)
    Rash 3/78 (3.8%) 3/82 (3.7%)
    Pruritis 2/78 (2.6%) 2/82 (2.4%)
    Rash macular 0/78 (0%) 1/82 (1.2%)
    Rash pruritic 0/78 (0%) 1/82 (1.2%)
    Skin ulcer 1/78 (1.3%) 0/82 (0%)
    Vascular disorders
    Embolism 0/78 (0%) 2/82 (2.4%)
    Hypertension 43/78 (55.1%) 42/82 (51.2%)
    Hypotension 7/78 (9%) 6/82 (7.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Chief Scientific Officer
    Organization Deverra Therapeutics
    Phone 206-519-5304
    Email cdelaney@deverratx.com
    Responsible Party:
    Nohla Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT01690520
    Other Study ID Numbers:
    • 2603.00
    • NCI-2012-01572
    • 2603
    • 2603.00
    • P30CA015704
    • P50HL110787
    First Posted:
    Sep 21, 2012
    Last Update Posted:
    Jul 6, 2021
    Last Verified:
    Jun 1, 2021