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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1City of Hope Comprehensive Cancer CenterDuarteCaliforniaUnited States91010
    2Stanford Cancer Institute Palo AltoPalo AltoCaliforniaUnited States94304
    3University of ColoradoDenverColoradoUnited States80217-3364
    4Dana-Farber Cancer InstituteBostonMassachusettsUnited States02215
    5Mount Sinai HospitalNew YorkNew YorkUnited States10029
    6Duke University Medical CenterDurhamNorth CarolinaUnited States27710
    7Cleveland Clinic FoundationClevelandOhioUnited States44195
    8Fred Hutch/University of Washington Cancer ConsortiumSeattleWashingtonUnited States98109

    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

    Study Results

    Participant Flow

    Recruitment DetailsThe 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 TitleArm I (Standard of Care)Arm II (Experimental)
    Arm/Group DescriptionCONDITIONING 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 transplantCONDITIONING 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
    STARTED7882
    Modified Intent to Treat (mITT)7880
    COMPLETED2735
    NOT COMPLETED5147

    Baseline Characteristics

    Arm/Group TitleArm I (Standard of Care)Arm II (Experimental)Total
    Arm/Group DescriptionCONDITIONING 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 transplantCONDITIONING 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 transplantTotal of all reporting groups
    Overall Participants7882160
    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
    TitleTime to Neutrophil Engraftment
    DescriptionFirst of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.
    Time FrameUp 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 TitleArm I (Standard of Care)Arm II (Experimental)
    Arm/Group DescriptionCONDITIONING 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 transplantCONDITIONING 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 Participants7275
    Median (95% Confidence Interval) [days]
    20.0
    22.0
    2. Secondary Outcome
    TitleTime to Platelet Engraftment (20k)
    DescriptionFirst 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 FrameUp 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 TitleArm I (Standard of Care)Arm II (Experimental)
    Arm/Group DescriptionCONDITIONING 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 transplantCONDITIONING 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 Participants6566
    Median (95% Confidence Interval) [days]
    40.0
    38.0
    3. Secondary Outcome
    TitleOverall Survival
    Description
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm I (Standard of Care)Arm II (Experimental)
    Arm/Group DescriptionCONDITIONING 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 transplantCONDITIONING 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 Participants7880
    Count of Participants [Participants]
    52
    66.7%
    57
    69.5%
    4. Secondary Outcome
    TitleNon-relapse Mortality
    Description
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm I (Standard of Care)Arm II (Experimental)
    Arm/Group DescriptionCONDITIONING 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 transplantCONDITIONING 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 Participants7880
    Count of Participants [Participants]
    16
    20.5%
    16
    19.5%
    5. Secondary Outcome
    TitleProportion of Patients With Severe Acute Graft Versus Host Disease
    Description
    Time FrameUp to 100 days post-transplant

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm I (Standard of Care)Arm II (Experimental)
    Arm/Group DescriptionCONDITIONING 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 transplantCONDITIONING 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 Participants7880
    Number (95% Confidence Interval) [proportion of participants]
    0.14
    0.2%
    0.16
    0.2%
    6. Secondary Outcome
    TitleProportion of Participants With Chronic Graft Versus Host Disease
    Description
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleArm I (Standard of Care)Arm II (Experimental)
    Arm/Group DescriptionCONDITIONING 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 transplantCONDITIONING 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 Participants7880
    Count of Participants [Participants]
    27
    34.6%
    23
    28%

    Adverse Events

    Time Frame84 days
    Adverse Event Reporting Description
    Arm/Group TitleArm I (Standard of Care)Arm II (Experimental)
    Arm/Group DescriptionCONDITIONING 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 transplantCONDITIONING 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 (%)# EventsAffected / at Risk (%)# Events
    Total25/78 (32.1%) 21/82 (25.6%)
    Serious Adverse Events
    Arm I (Standard of Care)Arm II (Experimental)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total48/78 (61.5%) 55/82 (67.1%)
    Blood and lymphatic system disorders
    Disseminated intravascular coagulation0/78 (0%) 1/82 (1.2%)
    Lymphatic disorder0/78 (0%) 1/82 (1.2%)
    Febrile neutropenia1/78 (1.3%) 1/82 (1.2%)
    Cardiac disorders
    Atrial flutter0/78 (0%) 1/82 (1.2%)
    Cardiac arrest0/78 (0%) 1/82 (1.2%)
    Cardiac failure0/78 (0%) 1/82 (1.2%)
    Pericardial effusion0/78 (0%) 1/82 (1.2%)
    Sinus bradycardia0/78 (0%) 1/82 (1.2%)
    Tachycardia1/78 (1.3%) 0/82 (0%)
    Gastrointestinal disorders
    Abdominal pain2/78 (2.6%) 1/82 (1.2%)
    Jejunal perforation0/78 (0%) 1/82 (1.2%)
    Lower gastrointestinal haemorrhage1/78 (1.3%) 0/82 (0%)
    Pancreatitis0/78 (0%) 1/82 (1.2%)
    Pneumatosis intestinalis0/78 (0%) 1/82 (1.2%)
    Diarrhoea1/78 (1.3%) 6/82 (7.3%)
    Colitis1/78 (1.3%) 1/82 (1.2%)
    Nausea3/78 (3.8%) 2/82 (2.4%)
    Vomiting2/78 (2.6%) 3/82 (3.7%)
    General disorders
    Pyrexia14/78 (17.9%) 17/82 (20.7%)
    Multiple organ dysfunction syndrome1/78 (1.3%) 2/82 (2.4%)
    Chest pain1/78 (1.3%) 0/82 (0%)
    Chills0/78 (0%) 1/82 (1.2%)
    Complication associated with device1/78 (1.3%) 0/82 (0%)
    Death0/78 (0%) 1/82 (1.2%)
    Non-cardiac chest pain1/78 (1.3%) 0/82 (0%)
    Hepatobiliary disorders
    Hepatic failure1/78 (1.3%) 0/82 (0%)
    Immune system disorders
    Acute graft versus host disease in intestine1/78 (1.3%) 2/82 (2.4%)
    Graft versus host disease in gastrointestinal tract2/78 (2.6%) 1/82 (1.2%)
    Hypersensitivity1/78 (1.3%) 0/82 (0%)
    Acute graft versus host disease in liver1/78 (1.3%) 1/82 (1.2%)
    Graft versus host disease5/78 (6.4%) 7/82 (8.5%)
    Infections and infestations
    Clostridium difficile infection0/78 (0%) 1/82 (1.2%)
    Cytomegalovirus gastritis0/78 (0%) 1/82 (1.2%)
    Cytomegalovirus infection1/78 (1.3%) 0/82 (0%)
    Eye infection0/78 (0%) 1/82 (1.2%)
    Herpes virus infection0/78 (0%) 1/82 (1.2%)
    Klebsiella infection0/78 (0%) 1/82 (1.2%)
    Oral infection0/78 (0%) 1/82 (1.2%)
    Pneumonia klebsiella1/78 (1.3%) 0/82 (0%)
    Pseudomonas infection1/78 (1.3%) 0/82 (0%)
    Rhinovirus infection1/78 (1.3%) 0/82 (0%)
    Sinusitis1/78 (1.3%) 0/82 (0%)
    Skin infection0/78 (0%) 1/82 (1.2%)
    Systemic candida0/78 (0%) 1/82 (1.2%)
    Urinary tract infection0/78 (0%) 1/82 (1.2%)
    Urinary tract infection enterococcal1/78 (1.3%) 0/82 (0%)
    Sepsis2/78 (2.6%) 5/82 (6.1%)
    Staphylococcal infection2/78 (2.6%) 2/82 (2.4%)
    BK virus infection1/78 (1.3%) 1/82 (1.2%)
    Cytomegalovirus viraemia0/78 (0%) 2/82 (2.4%)
    Lung infection2/78 (2.6%) 0/82 (0%)
    Pneumonia fungal1/78 (1.3%) 1/82 (1.2%)
    Staphylococcal bacteraemia0/78 (0%) 2/82 (2.4%)
    Injury, poisoning and procedural complications
    Infusion related reaction0/78 (0%) 3/82 (3.7%)
    Transplant failure1/78 (1.3%) 2/82 (2.4%)
    Subdural haematoma0/78 (0%) 1/82 (1.2%)
    Investigations
    Alanine aminotransferase increased0/78 (0%) 1/82 (1.2%)
    Aspartate aminotransferase increased0/78 (0%) 1/82 (1.2%)
    Blood bilirubin increased0/78 (0%) 1/82 (1.2%)
    Platelet count decreased0/78 (0%) 1/82 (1.2%)
    Metabolism and nutrition disorders
    Hyperuricaemia1/78 (1.3%) 0/82 (0%)
    Hypokalemia1/78 (1.3%) 0/82 (0%)
    Hypophosphataemia1/78 (1.3%) 0/82 (0%)
    Nervous system disorders
    Encephalopathy0/78 (0%) 1/82 (1.2%)
    Haemorrhage intracranial1/78 (1.3%) 0/82 (0%)
    Headache0/78 (0%) 1/82 (1.2%)
    Neuropathy peripheral1/78 (1.3%) 0/82 (0%)
    Posterior reversible encephalopathy syndrome1/78 (1.3%) 0/82 (0%)
    Seizure2/78 (2.6%) 0/82 (0%)
    Psychiatric disorders
    Delirium1/78 (1.3%) 0/82 (0%)
    Renal and urinary disorders
    Haematuria1/78 (1.3%) 0/82 (0%)
    Acute kidney injury4/78 (5.1%) 4/82 (4.9%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism1/78 (1.3%) 2/82 (2.4%)
    Acute respiratory distress syndrome0/78 (0%) 1/82 (1.2%)
    Cough1/78 (1.3%) 0/82 (0%)
    Dyspnoea1/78 (1.3%) 0/82 (0%)
    Organising pneumonia1/78 (1.3%) 0/82 (0%)
    Pleural effusion1/78 (1.3%) 0/82 (0%)
    Pulmonary alveolar haemorrhage1/78 (1.3%) 0/82 (0%)
    Pulmonary infarction0/78 (0%) 1/82 (1.2%)
    Pulmonary mass0/78 (0%) 1/82 (1.2%)
    Pulmonary oedema0/78 (0%) 1/82 (1.2%)
    Hypoxia4/78 (5.1%) 3/82 (3.7%)
    Respiratory failure4/78 (5.1%) 7/82 (8.5%)
    Skin and subcutaneous tissue disorders
    Skin ulcer0/78 (0%) 1/82 (1.2%)
    Vascular disorders
    Hypertension0/78 (0%) 1/82 (1.2%)
    Hypotension4/78 (5.1%) 3/82 (3.7%)
    Other (Not Including Serious) Adverse Events
    Arm I (Standard of Care)Arm II (Experimental)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total71/78 (91%) 73/82 (89%)
    Blood and lymphatic system disorders
    Haemolytic uraemic syndrome3/78 (3.8%) 3/82 (3.7%)
    Febrile neutropenia1/78 (1.3%) 1/82 (1.2%)
    Thrombotic microangiopathy1/78 (1.3%) 0/82 (0%)
    Thrombotic thrombocytopenic purpura0/78 (0%) 1/82 (1.2%)
    Haemolysis2/78 (2.6%) 1/82 (1.2%)
    Anaemia5/78 (6.4%) 2/82 (2.4%)
    Cardiac disorders
    Pericardial effusion2/78 (2.6%) 2/82 (2.4%)
    Cardiac failure1/78 (1.3%) 1/82 (1.2%)
    Bradycardia1/78 (1.3%) 0/82 (0%)
    Myocardial infarction0/78 (0%) 1/82 (1.2%)
    Tachycardia1/78 (1.3%) 0/82 (0%)
    Endocrine disorders
    Adrenal insufficiency1/78 (1.3%) 1/82 (1.2%)
    Gastrointestinal disorders
    Colitis7/78 (9%) 9/82 (11%)
    Enterocolitis2/78 (2.6%) 0/82 (0%)
    Gastritis1/78 (1.3%) 1/82 (1.2%)
    Gastrointestinal pain1/78 (1.3%) 1/82 (1.2%)
    Ileus2/78 (2.6%) 0/82 (0%)
    Large intestinal haemorrhage1/78 (1.3%) 1/82 (1.2%)
    Gastrointestinal haemorrhage1/78 (1.3%) 0/82 (0%)
    Impaired gastric emptying0/78 (0%) 1/82 (1.2%)
    Lower gastrointestinal haemorrhage1/78 (1.3%) 0/82 (0%)
    Oesophagitis1/78 (1.3%) 0/82 (0%)
    Periodontal disease1/78 (1.3%) 0/82 (0%)
    Proctitis0/78 (0%) 1/82 (1.2%)
    Stomatitis30/78 (38.5%) 36/82 (43.9%)
    Nausea15/78 (19.2%) 25/82 (30.5%)
    Diarrhoea11/78 (14.1%) 11/82 (13.4%)
    Vomiting5/78 (6.4%) 9/82 (11%)
    Abdominal pain8/78 (10.3%) 4/82 (4.9%)
    Pain8/78 (10.3%) 3/82 (3.7%)
    Pyrexia1/78 (1.3%) 2/82 (2.4%)
    General disorders
    Fatigue3/78 (3.8%) 1/82 (1.2%)
    Oedema peripheral0/78 (0%) 2/82 (2.4%)
    Chills0/78 (0%) 1/82 (1.2%)
    Mucosal inflammation0/78 (0%) 1/82 (1.2%)
    Multiple organ dysfunction syndrome1/78 (1.3%) 0/82 (0%)
    Pneumatosis1/78 (1.3%) 0/82 (0%)
    Immune system disorders
    Anaphylactic reaction1/78 (1.3%) 0/82 (0%)
    Graft versus host disease0/78 (0%) 1/82 (1.2%)
    Infections and infestations
    Enterococcal infection5/78 (6.4%) 3/82 (3.7%)
    Adenovirus infection4/78 (5.1%) 2/82 (2.4%)
    Alpha haemolytic streptococcal infection5/78 (6.4%) 1/82 (1.2%)
    Cystitis4/78 (5.1%) 2/82 (2.4%)
    Urinary tract infection3/78 (3.8%) 3/82 (3.7%)
    BK virus infection1/78 (1.3%) 3/82 (3.7%)
    Device related infection2/78 (2.6%) 2/82 (2.4%)
    Sinusitis2/78 (2.6%) 2/82 (2.4%)
    Skin infection1/78 (1.3%) 3/82 (3.7%)
    Candida infection2/78 (2.6%) 0/82 (0%)
    Encephalitis0/78 (0%) 2/82 (2.4%)
    Escherichia infection1/78 (1.3%) 1/82 (1.2%)
    Human polyomavirus infection2/78 (2.6%) 0/82 (0%)
    Pseudomonas infection1/78 (1.3%) 1/82 (1.2%)
    Sepsis1/78 (1.3%) 1/82 (1.2%)
    Stomatococcal infection1/78 (1.3%) 1/82 (1.2%)
    Upper respiratory tract infection2/78 (2.6%) 0/82 (0%)
    Actinomycotic sepsis1/78 (1.3%) 0/82 (0%)
    Administration site cellulitis1/78 (1.3%) 0/82 (0%)
    Bacillus infection1/78 (1.3%) 0/82 (0%)
    Bacteraemia1/78 (1.3%) 0/82 (0%)
    Coronavirus infection1/78 (1.3%) 0/82 (0%)
    Corynebacterium infection1/78 (1.3%) 0/82 (0%)
    Cytomegalovirus colitis1/78 (1.3%) 0/82 (0%)
    Enterobacter infection1/78 (1.3%) 0/82 (0%)
    Enterocolitis infection1/78 (1.3%) 0/82 (0%)
    Escherichia bacteraemia0/78 (0%) 1/82 (1.2%)
    Fusobacterium infection0/78 (0%) 1/82 (1.2%)
    Gastric infection1/78 (1.3%) 0/82 (0%)
    Influenza1/78 (1.3%) 0/82 (0%)
    Leuconostoc infection0/78 (0%) 1/82 (1.2%)
    Lip infection0/78 (0%) 1/82 (1.2%)
    Osteomyelitis1/78 (1.3%) 0/82 (0%)
    Wound infection1/78 (1.3%) 0/82 (0%)
    Staphylococcal infection7/78 (9%) 5/82 (6.1%)
    Lung infection7/78 (9%) 6/82 (7.3%)
    Human herpesvirus 6 infection6/78 (7.7%) 5/82 (6.1%)
    Cytomegalovirus infection2/78 (2.6%) 7/82 (8.5%)
    Streptococcal infection7/78 (9%) 2/82 (2.4%)
    Bacterial infection4/78 (5.1%) 1/82 (1.2%)
    Clostridium difficile infection3/78 (3.8%) 0/82 (0%)
    Injury, poisoning and procedural complications
    Infusion related reaction0/78 (0%) 1/82 (1.2%)
    Post procedural haemorrhage1/78 (1.3%) 0/82 (0%)
    Radiation skin injury1/78 (1.3%) 0/82 (0%)
    Tracheal haemorrhage1/78 (1.3%) 0/82 (0%)
    Investigations
    Blood bilirubin increased11/78 (14.1%) 8/82 (9.8%)
    Alanine aminotransferase increased3/78 (3.8%) 3/82 (3.7%)
    Aspartate aminotransferase increased2/78 (2.6%) 2/82 (2.4%)
    Blood aluminium increased1/78 (1.3%) 3/82 (3.7%)
    Blood alkaline phosphatase increased1/78 (1.3%) 1/82 (1.2%)
    Weight decreased2/78 (2.6%) 0/82 (0%)
    White blood cell count increased0/78 (0%) 2/82 (2.4%)
    Electrocardiogram QT prolonged1/78 (1.3%) 0/82 (0%)
    Urine output decreased0/78 (0%) 1/82 (1.2%)
    Weight increased1/78 (1.3%) 0/82 (0%)
    Platelet count decreased13/78 (16.7%) 9/82 (11%)
    Neutrophil count decreased8/78 (10.3%) 3/82 (3.7%)
    White blood cell count decreased4/78 (5.1%) 1/82 (1.2%)
    Blood creatinine increased1/78 (1.3%) 6/82 (7.3%)
    Metabolism and nutrition disorders
    Decreased appetite39/78 (50%) 38/82 (46.3%)
    Hypokalemia14/78 (17.9%) 14/82 (17.1%)
    Hyperglycaemia8/78 (10.3%) 12/82 (14.6%)
    Hyponatraemia9/78 (11.5%) 10/82 (12.2%)
    Hypophosphataemia6/78 (7.7%) 10/82 (12.2%)
    Hypertriglyceridaemia3/78 (3.8%) 5/82 (6.1%)
    Hyperkalaemia3/78 (3.8%) 3/82 (3.7%)
    Hypocalcaemia2/78 (2.6%) 2/82 (2.4%)
    Acidosis1/78 (1.3%) 1/82 (1.2%)
    Hypermagnesaemia1/78 (1.3%) 1/82 (1.2%)
    Hypernatraemia1/78 (1.3%) 1/82 (1.2%)
    Iron overload1/78 (1.3%) 1/82 (1.2%)
    Dehydration1/78 (1.3%) 0/82 (0%)
    Hyperuricaemia0/78 (0%) 1/82 (1.2%)
    Hypoalbuminaemia0/78 (0%) 1/82 (1.2%)
    Hypomagnesaemia1/78 (1.3%) 0/82 (0%)
    Musculoskeletal and connective tissue disorders
    Bone pain1/78 (1.3%) 1/82 (1.2%)
    Back pain1/78 (1.3%) 0/82 (0%)
    Muscular weakness1/78 (1.3%) 0/82 (0%)
    Myalgia1/78 (1.3%) 0/82 (0%)
    Pain in extremity3/78 (3.8%) 0/82 (0%)
    Nervous system disorders
    Seizure1/78 (1.3%) 1/82 (1.2%)
    Tremor0/78 (0%) 2/82 (2.4%)
    Cognitive disorder0/78 (0%) 1/82 (1.2%)
    Dysaesthesia0/78 (0%) 1/82 (1.2%)
    Myoclonus1/78 (1.3%) 0/82 (0%)
    Somnolence1/78 (1.3%) 0/82 (0%)
    Headache9/78 (11.5%) 5/82 (6.1%)
    Peripheral motor neuropathy1/78 (1.3%) 2/82 (2.4%)
    Syncope1/78 (1.3%) 2/82 (2.4%)
    Psychiatric disorders
    Depression3/78 (3.8%) 1/82 (1.2%)
    Insomnia1/78 (1.3%) 3/82 (3.7%)
    Anxiety1/78 (1.3%) 1/82 (1.2%)
    Confusional state1/78 (1.3%) 0/82 (0%)
    Delirium1/78 (1.3%) 0/82 (0%)
    Renal and urinary disorders
    Acute kidney injury1/78 (1.3%) 3/82 (3.7%)
    Chronic kidney disease0/78 (0%) 1/82 (1.2%)
    Urinary tract pain1/78 (1.3%) 0/82 (0%)
    Haematuria5/78 (6.4%) 4/82 (4.9%)
    Reproductive system and breast disorders
    Menorrhagia0/78 (0%) 2/82 (2.4%)
    Vulvovaginal inflammation1/78 (1.3%) 0/82 (0%)
    Vaginal haemorrhage1/78 (1.3%) 2/82 (2.4%)
    Respiratory, thoracic and mediastinal disorders
    Pharyngeal inflammation2/78 (2.6%) 0/82 (0%)
    Pneumonitis1/78 (1.3%) 1/82 (1.2%)
    Acute respiratory distress syndrome1/78 (1.3%) 0/82 (0%)
    Cough1/78 (1.3%) 0/82 (0%)
    Organising pneumonia1/78 (1.3%) 0/82 (0%)
    Pleural effusion1/78 (1.3%) 0/82 (0%)
    Pneumothorax0/78 (0%) 1/82 (1.2%)
    Pulmonary oedema1/78 (1.3%) 0/82 (0%)
    Stridor0/78 (0%) 1/82 (1.2%)
    Epistaxis6/78 (7.7%) 6/82 (7.3%)
    Dyspnoea1/78 (1.3%) 2/82 (2.4%)
    Hypoxia8/78 (10.3%) 9/82 (11%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular37/78 (47.4%) 40/82 (48.8%)
    Rash3/78 (3.8%) 3/82 (3.7%)
    Pruritis2/78 (2.6%) 2/82 (2.4%)
    Rash macular0/78 (0%) 1/82 (1.2%)
    Rash pruritic0/78 (0%) 1/82 (1.2%)
    Skin ulcer1/78 (1.3%) 0/82 (0%)
    Vascular disorders
    Embolism0/78 (0%) 2/82 (2.4%)
    Hypertension43/78 (55.1%) 42/82 (51.2%)
    Hypotension7/78 (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/TitleChief Scientific Officer
    OrganizationDeverra Therapeutics
    Phone206-519-5304
    Emailcdelaney@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