Clincosm LogoSign in Get a demo

Alvocidib Biomarker-driven Phase 2 AML Study

Sponsor
Sumitomo Pharma Oncology, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02520011
Collaborator
(none)
104
Enrollment
38
Locations
2
Arms
47
Actual Duration (Months)
2.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this two-stage Phase 2 study is to assess the clinical response (Complete Remission) of ACM (Alvocidib/Cytarabine/Mitoxantrone) compared to CM (Cytarabine/Mitoxantrone) treatment in refractory or relapsed AML patients with demonstrated MCL-1 dependence of ≥ 30% by mitochondrial profiling in bone marrow.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

In Stage 1 of the study, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 30% by mitochondrial profiling in bone marrow will receive treatment with ACM.

In Stage 2, all eligible AML patients with demonstrated MCL-1 dependence of ≥ 30% by mitochondrial profiling in bone marrow will be randomized 1:1 to receive either treatment with ACM or CM.

Study Design

Study Type:
Interventional
Actual Enrollment :
104 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 2, Randomized, Biomarker-driven Clinical Study in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With MCL-1 Dependence ≥30%
Actual Study Start Date :
Mar 14, 2016
Actual Primary Completion Date :
Feb 12, 2020
Actual Study Completion Date :
Feb 12, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: ACM (Stage 1 / Stage 2)

A: alvocidib, 30 mg/m2 as a 30 minute intravenous (IV) bolus followed by 60 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3; C: cytarabine (ara-c), 2 gm/m2 by continuous IV infusion over 72 hours on Days 6-8; M: mitoxantrone (mitoxantrone hydrochloride), 40 mg/m2 by IV infusion over 1-2 hours starting 12 hours after completing cytarabine

Drug: Alvocidib

Drug: Cytarabine
Other Names:
  • ara-c

    • Drug: Mitoxantrone
    Other Names:
  • mitoxantrone hydrochloride

    		•
    Active Comparator: CM (Stage 2)

    C: cytarabine (ara-c), 2 gm/m2 by continuous IV infusion over 72 hours on Days 1-3; M: mitoxantrone (mitoxantrone hydrochloride), 40 mg/m2 by IV infusion over 1-2 hours starting 12 hours after completing cytarabine

    Drug: Cytarabine
    Other Names:
  • ara-c

    • Drug: Mitoxantrone
    Other Names:
  • mitoxantrone hydrochloride

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Complete Response (CR) Rate in Patients With Relapsed or Refractory AML [Best response after at least 1 cycle through study completion approximately 4 years]

      Complete Remission (CR) rate = Percentage of patients achieving CR after Cycle 1 as defined in Stage 1 by the International Working Group (IWG) Criteria and 2010 European LeukemiaNet (EN) criteria in patients with relapsed or refractory AML with MCL-1 dependence >30% and in Stage 2 by the 2017 ELN criteria. The study was terminated in January 2020 due to a steady and marked reduction in enrollment. Thus, the efficacy endpoints could not be analyzed. As sufficient efficacy results were not available to analyze patients based on the percentage of MCL-1 dependency the treatment efficacy was summarized by distributing the safety population into 6 groups based on whether the patients received the ACM vs CM regimen and their disease stages at study entry.

    Other Outcome Measures

    1. Response to Treatment [Best response after at least 1 cycle through study completion approximately 4 years]

      To determine if treatment with ACM can induce CR in patients with relapsed or refractory AML with MCL-1 dependence of >30% who failed to achieve CR following 1 cycle of CM

    Eligibility Criteria

    Criteria

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

    1. Be between the ages of ≥18 and ≤65 years

    2. Have an established, pathologically confirmed diagnoses of AML by World Health Organization (WHO) criteria excluding acute promyelocytic leukemia (APL-M3) with a bone marrow of >5% blasts based on histology or flow cytometry

    3. Be in first relapse (within 24 months of CR) or have failed induction therapy* (no CR or CRi after treatment with an intensive regimen (eg, anthracycline/cytarabine ± etoposide, gemtuzumab ozogamicin, or cladribine).

    *Induction therapy may involve 1 or 2 cycles of the same regimen. Efficacy assessment of induction therapy must be >21 days from the start of the previous induction cycle.

    1. Demonstrate MCL-1 dependence of ≥30% by mitochondrial profiling in bone marrow.

    2. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2

    3. Have a serum creatinine level ≤1.8 mg/dL

    4. Have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN)

    5. Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia)

    6. Have a left ventricular ejection fraction (LVEF) >45% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan

    7. Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate during and for at least 6 months after completion of study therapy.

    8. Be able to comply with the requirements of the entire study.

    9. Provide written informed consent prior to any study related procedure.

    Exclusion Criteria:

    1. Received more than 2 cycles of induction therapy for AML. Investigational agents as part of front-line therapy for AML may by acceptable following discussion with the Medical Monitor. Hydroxyurea is permitted (see #5 below).

    2. Received any previous treatment with alvocidib or any other CDK inhibitor

    3. Received a hematopoietic stem cell transplant within the previous 2 months

    4. Have clinically significant graft versus host disease (GVHD), or GVHD requiring initiation or escalation of treatment within the last 21 days

    5. Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting treatment on either arm.

    6. Received >360 mg/m2 equivalents of daunorubicin

    7. Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #5 above)

    8. Received antileukemic therapy within the last 3 weeks (with the exception of hydroxyurea or if the patient has definite refractory disease). Refractory patients who received therapy within the last 3 weeks may be eligible with prior approval of the Medical Monitor.

    9. Diagnosed with acute promyelocytic leukemia (APL, M3)

    10. Have active central nervous system (CNS) leukemia

    11. Have evidence of uncontrolled disseminated intravascular coagulation

    12. Have an active, uncontrolled infection

    13. Have other life-threatening illness

    14. Have other active malignancies or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia

    15. Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.

    16. Are pregnant and/or nursing

    17. Have received any live vaccine within 14 days prior to first study drug administration.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Honor Health Research Institute Scottsdale Arizona United States 85258
    2 University of California Los Angeles (UCLA) Los Angeles California United States 90095
    3 University of California San Diego UCSD San Diego California United States 92093-2024
    4 Mayo Clinic Florida Jacksonville Florida United States 32224
    5 Northside Hospital Atlanta Georgia United States 30342
    6 Northwestern Memorial Hospital Chicago Illinois United States 60611
    7 University of Iowa Iowa City Iowa United States 52242
    8 University of Kansas Medical Center Westwood Kansas United States 66205
    9 Ochsner Clinic Foundation New Orleans Louisiana United States 70121
    10 Sidney Kimmel Cancer Center at Johns Hopkins Baltimore Maryland United States 21287
    11 University of Michigan Ann Arbor Michigan United States 48109
    12 Mayo Clinic Rochester Rochester Minnesota United States 55905
    13 University of Nebraska Medical Center Omaha Nebraska United States 68198
    14 Morristown Cancer Center Morristown New Jersey United States 07960
    15 Roswell Park Cancer Center Institute Buffalo New York United States 14263
    16 Hudson Valley Cancer Center Hawthorne New York United States 10532
    17 Columbia University Medical Center New York New York United States 10032
    18 University of North Carolina Chapel Hill North Carolina United States 27599
    19 Duke Durham North Carolina United States 27710
    20 East Carolina University Greenville North Carolina United States 27858
    21 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    22 Ohio State University Columbus Ohio United States 43210
    23 West Penn Allegheny Hospital Pittsburgh Pennsylvania United States 15224
    24 Baylor Sammons Cancer Center Dallas Texas United States 75246
    25 MD Anderson Cancer Center Houston Texas United States 77030
    26 Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    27 Princess Margaret Cancer Center Toronto Ontario Canada M5G 2M9
    28 Hospital Regional Universitario de Malaga Málaga Malaga Spain 29010
    29 Complejo Hospitalario Universitario de Albacete Albacete Spain 02006
    30 Institut Catala d'Oncologia Badalona Spain
    31 Hospital Clinic de Barcelona Barcelona Spain 08036
    32 Hospital San Pedro de Alcantara Cáceres Spain
    33 Hospital Universitario Central de Asturias - HUCA Oviedo Spain 33011
    34 Hospital Clinico Universitario de Salamanca Salamanca Spain 37007
    35 Hospital Universitari i Politècnic La Fe Valencia Spain
    36 University Hospitals of Wales Cardiff Wales United Kingdom CF10 3NS
    37 Univ Hospital of Bristol Bristol United Kingdom
    38 Guys Hospital St. Thomas London United Kingdom

    Sponsors and Collaborators

    • Sumitomo Pharma Oncology, Inc.

    Investigators

    • Study Director: Stephen Anthony, DO, Sumitomo Pharma Oncology, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Sumitomo Pharma Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02520011
    Other Study ID Numbers:
    • TPI-ALV-201
    First Posted:
    Aug 11, 2015
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Sumitomo Pharma Oncology, Inc.
    Refractory AML
    Relapsed AML
    AML
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Cytarabine
    Mitoxantrone
    Alvocidib

    Study Results

    Participant Flow

    Recruitment Details Enrolled 104 pts from 14Mar2016 to 12Feb2020 at 22 of 40 sites. Patients were hospitalized until completion of their chemotherapy. The study terminated early in Jan2020 due to a steady and marked reduction in enrollment. The study protocol underwent a few major amendments during the course of the trial. Although the study protocol and the SAP had planned for comprehensive analysis of the efficacy data, only select efficacy analyses could be performed due to early termination of the trial.
    Pre-assignment Detail
    Arm/Group Title CM Relapsed/Refractory ACM Relapsed/Refractory ACM Newly Diagnosed
    Arm/Group Description Patients who were relapsed/refractory AML and were enrolled during Stage 2 and received Cytarabine 2 gm/m2 by continuous infusion over 72 hours on Days 1-3 and Mitoxantrone 40 mg/m2 by IV over 1-2 hours starting 12 hours after completing cytarabine. Patients who had relapsed/refractory AML and were enrolled during Stage 1 and Stage 2 and received Alvocidib 30 mg/m2 as a 30-minute intravenous bolus followed by 60 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3 with Cytarabine 2 gm/m2 by continuous IV infusion on Days 6-8 and Mitoxantrone 40 mg/m2 by IV infusion over 1-2 hours starting 12 hours after completing cytarabine. Patients who were newly diagnosed AML and enrolled during Stage 1 and Stage 2 and received Alvocidib 30 mg/m2 as a 30-minute intravenous bolus followed by 60 mg/m2 over 4 hours as an IV infusion administered daily on Days 1-3 with Cytarabine 2 gm/m2 by continuous IV infusion on Days 6-8 and Mitoxantrone 40 mg/m2 by IV infusion over 1-2 hours starting 12 hours after completing cytarabine.
    Period Title: Overall Study
    STARTED 11 79 14
    Stage 1 0 32 10
    Stage 2 11 47 4
    COMPLETED 6 33 5
    NOT COMPLETED 5 46 9

    Baseline Characteristics

    Arm/Group Title CM Relapsed/Refractory ACM Relapsed/Refractory ACM Newly Diagnosed Total
    Arm/Group Description Stage 2 Relapsed/Refractory AML patients who were randomized to receive CM Relapsed/Refractory AML patients enrolled to Stage 1 and those enrolled to Stage 2 who received ACM. Newly diagnosed AML patients enrolled and received ACM. Total of all reporting groups
    Overall Participants 11 79 14 104
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    11
    100%
    79
    100%
    14
    100%
    104
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    4
    36.4%
    40
    50.6%
    3
    21.4%
    47
    45.2%
    Male
    7
    63.6%
    39
    49.4%
    11
    78.6%
    57
    54.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    2
    2.5%
    0
    0%
    2
    1.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    4
    5.1%
    0
    0%
    4
    3.8%
    White
    11
    100%
    70
    88.6%
    13
    92.9%
    94
    90.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    3
    3.8%
    1
    7.1%
    4
    3.8%
    2017 ELN genetic risk criteria classification (Count of Participants)
    Adverse
    8
    72.7%
    26
    32.9%
    3
    21.4%
    37
    35.6%
    Intermediate
    1
    9.1%
    13
    16.5%
    0
    0%
    14
    13.5%
    Favorable
    2
    18.2%
    6
    7.6%
    1
    7.1%
    9
    8.7%
    Missing
    0
    0%
    34
    43%
    10
    71.4%
    44
    42.3%

    Outcome Measures

    1. Primary Outcome
    Title Complete Response (CR) Rate in Patients With Relapsed or Refractory AML
    Description Complete Remission (CR) rate = Percentage of patients achieving CR after Cycle 1 as defined in Stage 1 by the International Working Group (IWG) Criteria and 2010 European LeukemiaNet (EN) criteria in patients with relapsed or refractory AML with MCL-1 dependence >30% and in Stage 2 by the 2017 ELN criteria. The study was terminated in January 2020 due to a steady and marked reduction in enrollment. Thus, the efficacy endpoints could not be analyzed. As sufficient efficacy results were not available to analyze patients based on the percentage of MCL-1 dependency the treatment efficacy was summarized by distributing the safety population into 6 groups based on whether the patients received the ACM vs CM regimen and their disease stages at study entry.
    Time Frame Best response after at least 1 cycle through study completion approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Stage 2 CM Relapsed/Refractory Stage 2 ACM Relapsed/Refractory Stage 1 ACM Relapsed/Refractory Stages 1 and 2 ACM Relapsed/Refractory Stage 1 Newly Diagnosed ACM All Stages and Cohorts (Including Randomized Stage): ACM Total
    Arm/Group Description Stage 2 Relapsed/Refractory AML patients who were randomized to receive CM Stage 2 Relapsed/Refractory AML patients who were randomized to receive ACM Stage 1 Relapsed/Refractory AML patients received ACM Stages 1 and 2 Relapsed/Refractory AML patients combined who received ACM Stage 1 Newly Diagnosed AML patients who received ACM Total patients who received ACM (Stages 1 and 2 Relapsed/Refractory AML patients and Newly Diagnosed patients combined)"
    Measure Participants 11 11 25 79 14 93
    Complete Remission (CR)
    6
    54.5%
    2
    2.5%
    8
    57.1%
    21
    20.2%
    6
    NaN
    27
    NaN
    CR with Incomplete Neutrophil Recovery (Cri)
    0
    0%
    3
    3.8%
    5
    35.7%
    15
    14.4%
    2
    NaN
    17
    NaN
    Partial Remission (PR)
    0
    0%
    0
    0%
    1
    7.1%
    1
    1%
    1
    NaN
    2
    NaN
    Resistant/Relapsed Disease
    5
    45.5%
    5
    6.3%
    5
    35.7%
    30
    28.8%
    4
    NaN
    34
    NaN
    Not Evaluated
    0
    0%
    1
    1.3%
    6
    42.9%
    12
    11.5%
    1
    NaN
    13
    NaN
    2. Other Pre-specified Outcome
    Title Response to Treatment
    Description To determine if treatment with ACM can induce CR in patients with relapsed or refractory AML with MCL-1 dependence of >30% who failed to achieve CR following 1 cycle of CM
    Time Frame Best response after at least 1 cycle through study completion approximately 4 years

    Outcome Measure Data

    Analysis Population Description
    A total 11 patients were initially randomized to the CM arm. 6 had CR from receiving CM so they did not cross over to receive ACM. Of the remaining 5 patients, only 2 crossed over to receive ACM and were included in the analysis of this outcome.
    Arm/Group Title Stage 2 CM Relapsed/Refractory AML
    Arm/Group Description A total 11 patients were initially randomized to the CM arm. 6 had CR from receiving CM so they did not cross over to receive ACM. Of the remaining 5 patients, only 2 crossed over to receive ACM and were included in the analysis of this outcome.
    Measure Participants 2
    Partial Remission (PR)
    1
    9.1%
    Not Evaluated
    1
    9.1%

    Adverse Events

    Time Frame Beginning at 1st dose of study drug through 30 days of the last administration of study drug, up to 4 years.
    Adverse Event Reporting Description
    Arm/Group Title CM Relapsed/Refractory ACM Relapsed/Refractory ACM Newly Diagnosed ACM Total
    Arm/Group Description CM Relapse/Refractory patients who received at least 1 dose of study drug ACM Relapsed/Refractory patients who received at least 1 dose of study drug ACM Newly Diagnosed patients who received at least 1 dose of study drug ACM Total patients who received at least 1 dose of study drug
    All Cause Mortality
    CM Relapsed/Refractory ACM Relapsed/Refractory ACM Newly Diagnosed ACM Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/11 (9.1%) 11/79 (13.9%) 1/14 (7.1%) 12/93 (12.9%)
    Serious Adverse Events
    CM Relapsed/Refractory ACM Relapsed/Refractory ACM Newly Diagnosed ACM Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/11 (27.3%) 31/79 (39.2%) 4/14 (28.6%) 35/93 (37.6%)
    Blood and lymphatic system disorders
    Bone marrow failure 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Disseminated intravascular coagulation 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Cardiac disorders
    Cardiac failure 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Left ventricular dysfunction 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Mitral valve incompetence 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Pericarditis 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Gastrointestinal disorders
    Colitis 0/11 (0%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Diarrhoea 0/11 (0%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Haematemesis 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Neutropenic colitis 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Upper gastrointestinal haemorrhage 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    General disorders
    Disease progression 0/11 (0%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Hepatobiliary disorders
    Liver injury 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Immune system disorders
    Cytokine release syndrome 0/11 (0%) 3/79 (3.8%) 1/14 (7.1%) 4/93 (4.3%)
    Infections and infestations
    Sepsis 2/11 (18.2%) 11/79 (13.9%) 1/14 (7.1%) 12/93 (12.9%)
    Lung infection 0/11 (0%) 3/79 (3.8%) 1/14 (7.1%) 4/93 (4.3%)
    Bacteraemia 0/11 (0%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Septic shock 0/11 (0%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Abscess neck 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Anorectal infection 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Bacterial sepsis 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Device related infection 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Enterocolitis infectious 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Enterocolitis viral 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Klebsiella sepsis 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Pneumonia 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Pneumonia fungal 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Pneumonia viral 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Staphylococcal bacteraemia 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Injury, poisoning and procedural complications
    Transfusion reaction 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Metabolism and nutrition disorders
    Tumour lysis syndrome 0/11 (0%) 3/79 (3.8%) 0/14 (0%) 3/93 (3.2%)
    Nervous system disorders
    Syncope 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Haemorrhage intracranial 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Psychiatric disorders
    Suicide attempt 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Completed suicide 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/11 (0%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Hypoxia 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Obstructive airways disorder 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Pneumomediastinum 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Pulmonary oedema 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Respiratory distress 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Skin and subcutaneous tissue disorders
    Subcutaneous emphysema 0/11 (0%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Vascular disorders
    Hypotension 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Other (Not Including Serious) Adverse Events
    CM Relapsed/Refractory ACM Relapsed/Refractory ACM Newly Diagnosed ACM Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/11 (100%) 79/79 (100%) 14/14 (100%) 93/93 (100%)
    Blood and lymphatic system disorders
    Febrile neutropenia 4/11 (36.4%) 42/79 (53.2%) 6/14 (42.9%) 48/93 (51.6%)
    Anaemia 2/11 (18.2%) 25/79 (31.6%) 2/14 (14.3%) 27/93 (29%)
    Leukopenia 0/11 (0%) 7/79 (8.9%) 5/14 (35.7%) 12/93 (12.9%)
    Neutropenia 0/11 (0%) 7/79 (8.9%) 1/14 (7.1%) 8/93 (8.6%)
    Thrombocytopenia 0/11 (0%) 6/79 (7.6%) 2/14 (14.3%) 8/93 (8.6%)
    Lymphopenia 0/11 (0%) 1/79 (1.3%) 3/14 (21.4%) 4/93 (4.3%)
    Splenic haematoma 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Cardiac disorders
    Sinus tachycardia 1/11 (9.1%) 9/79 (11.4%) 4/14 (28.6%) 13/93 (14%)
    Tachycardia 0/11 (0%) 7/79 (8.9%) 2/14 (14.3%) 9/93 (9.7%)
    Sinus bradycardia 0/11 (0%) 3/79 (3.8%) 2/14 (14.3%) 5/93 (5.4%)
    Atrial fibrillation 0/11 (0%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Left ventricular dysfunction 0/11 (0%) 0/79 (0%) 2/14 (14.3%) 2/93 (2.2%)
    Ear and labyrinth disorders
    Cerumen impaction 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Eye disorders
    Dry eye 2/11 (18.2%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Mydriasis 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Ocular discomfort 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Gastrointestinal disorders
    Diarrhoea 6/11 (54.5%) 66/79 (83.5%) 11/14 (78.6%) 77/93 (82.8%)
    Nausea 8/11 (72.7%) 44/79 (55.7%) 9/14 (64.3%) 53/93 (57%)
    Vomiting 2/11 (18.2%) 31/79 (39.2%) 7/14 (50%) 38/93 (40.9%)
    Abdominal pain 1/11 (9.1%) 22/79 (27.8%) 6/14 (42.9%) 28/93 (30.1%)
    Constipation 4/11 (36.4%) 16/79 (20.3%) 5/14 (35.7%) 21/93 (22.6%)
    Stomatitis 0/11 (0%) 14/79 (17.7%) 3/14 (21.4%) 17/93 (18.3%)
    Dry mouth 2/11 (18.2%) 10/79 (12.7%) 1/14 (7.1%) 11/93 (11.8%)
    Haemorrhoids 1/11 (9.1%) 5/79 (6.3%) 3/14 (21.4%) 8/93 (8.6%)
    Abdominal distension 1/11 (9.1%) 7/79 (8.9%) 0/14 (0%) 7/93 (7.5%)
    Gastrooesophageal reflux disease 1/11 (9.1%) 6/79 (7.6%) 1/14 (7.1%) 7/93 (7.5%)
    Colitis 1/11 (9.1%) 4/79 (5.1%) 2/14 (14.3%) 6/93 (6.5%)
    Proctalgia 1/11 (9.1%) 5/79 (6.3%) 1/14 (7.1%) 6/93 (6.5%)
    Abdominal pain upper 1/11 (9.1%) 5/79 (6.3%) 0/14 (0%) 5/93 (5.4%)
    Dyspepsia 0/11 (0%) 4/79 (5.1%) 1/14 (7.1%) 5/93 (5.4%)
    Ileus 0/11 (0%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Rectal haemorrhage 0/11 (0%) 2/79 (2.5%) 2/14 (14.3%) 4/93 (4.3%)
    Oral disorder 1/11 (9.1%) 3/79 (3.8%) 0/14 (0%) 3/93 (3.2%)
    Gastrointestinal pain 1/11 (9.1%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Gingival bleeding 1/11 (9.1%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Dysphagia 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Haemorrhoidal haemorrhage 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Large intestinal obstruction 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Salivary gland disorder 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Odynophagia 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    General disorders
    Oedema peripheral 1/11 (9.1%) 29/79 (36.7%) 7/14 (50%) 36/93 (38.7%)
    Pyrexia 1/11 (9.1%) 31/79 (39.2%) 5/14 (35.7%) 36/93 (38.7%)
    Fatigue 1/11 (9.1%) 29/79 (36.7%) 5/14 (35.7%) 34/93 (36.6%)
    Chills 1/11 (9.1%) 10/79 (12.7%) 4/14 (28.6%) 14/93 (15.1%)
    Mucosal inflammation 1/11 (9.1%) 9/79 (11.4%) 0/14 (0%) 9/93 (9.7%)
    Chest pain 0/11 (0%) 5/79 (6.3%) 0/14 (0%) 5/93 (5.4%)
    Malaise 0/11 (0%) 3/79 (3.8%) 1/14 (7.1%) 4/93 (4.3%)
    Non-cardiac chest pain 1/11 (9.1%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Oedema 1/11 (9.1%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Pain 0/11 (0%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Face oedema 0/11 (0%) 2/79 (2.5%) 1/14 (7.1%) 3/93 (3.2%)
    Disease progression 1/11 (9.1%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Generalised oedema 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Drug withdrawal syndrome 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Facial pain 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Asthenia 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/11 (0%) 4/79 (5.1%) 1/14 (7.1%) 5/93 (5.4%)
    Immune system disorders
    Cytokine release syndrome 0/11 (0%) 4/79 (5.1%) 1/14 (7.1%) 5/93 (5.4%)
    Graft versus host disease 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Infections and infestations
    Sepsis 2/11 (18.2%) 13/79 (16.5%) 3/14 (21.4%) 16/93 (17.2%)
    Lung infection 1/11 (9.1%) 6/79 (7.6%) 3/14 (21.4%) 8/93 (8.6%)
    Pneumonia 1/11 (9.1%) 6/79 (7.6%) 2/14 (14.3%) 8/93 (8.6%)
    Device related infection 0/11 (0%) 5/79 (6.3%) 1/14 (7.1%) 6/93 (6.5%)
    Sinusitis 0/11 (0%) 6/79 (7.6%) 0/14 (0%) 6/93 (6.5%)
    Enterococcal infection 0/11 (0%) 5/79 (6.3%) 0/14 (0%) 5/93 (5.4%)
    Respiratory syncytial virus infection 0/11 (0%) 5/79 (6.3%) 0/14 (0%) 5/93 (5.4%)
    Staphylococcal bacteraemia 0/11 (0%) 5/79 (6.3%) 0/14 (0%) 5/93 (5.4%)
    Bacteraemia 0/11 (0%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Clostridium difficile colitis 0/11 (0%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Folliculitis 0/11 (0%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Oral herpes 1/11 (9.1%) 3/79 (3.8%) 1/14 (7.1%) 4/93 (4.3%)
    Anorectal infection 0/11 (0%) 1/79 (1.3%) 2/14 (14.3%) 3/93 (3.2%)
    Urinary tract infection 1/11 (9.1%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Cystitis 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Cytomegalovirus infection 1/11 (9.1%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Enterobacter bacteraemia 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Gastroenteritis Escherichia coli 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Pneumonia legionella 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Bronchiolitis 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Groin abscess 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Herpes virus infection 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Hordeolum 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Pneumonia mycoplasmal 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Injury, poisoning and procedural complications
    Transfusion reaction 0/11 (0%) 8/79 (10.1%) 5/14 (35.7%) 13/93 (14%)
    Contusion 0/11 (0%) 6/79 (7.6%) 1/14 (7.1%) 7/93 (7.5%)
    Infusion related reaction 0/11 (0%) 5/79 (6.3%) 2/14 (14.3%) 7/93 (7.5%)
    Procedural pain 0/11 (0%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Fall 0/11 (0%) 2/79 (2.5%) 1/14 (7.1%) 3/93 (3.2%)
    Incision site erythema 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Toxicity to various agents 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Investigations
    White blood cell count decreased 1/11 (9.1%) 27/79 (34.2%) 4/14 (28.6%) 31/93 (33.3%)
    Alanine aminotransferase increased 1/11 (9.1%) 19/79 (24.1%) 4/14 (28.6%) 23/93 (24.7%)
    Platelet count decreased 1/11 (9.1%) 18/79 (22.8%) 4/14 (28.6%) 22/93 (23.7%)
    Aspartate aminotransferase increased 1/11 (9.1%) 19/79 (24.1%) 2/14 (14.3%) 21/93 (22.6%)
    Lymphocyte count decreased 2/11 (18.2%) 13/79 (16.5%) 4/14 (28.6%) 17/93 (18.3%)
    Neutrophil count decreased 0/11 (0%) 12/79 (15.2%) 1/14 (7.1%) 13/93 (14%)
    Weight decreased 0/11 (0%) 8/79 (10.1%) 3/14 (21.4%) 11/93 (11.8%)
    Blood bilirubin increased 2/11 (18.2%) 6/79 (7.6%) 3/14 (21.4%) 9/93 (9.7%)
    Blood creatinine increased 0/11 (0%) 6/79 (7.6%) 0/14 (0%) 6/93 (6.5%)
    International normalised ratio increased 0/11 (0%) 6/79 (7.6%) 0/14 (0%) 6/93 (6.5%)
    Blood lactate dehydrogenase increased 0/11 (0%) 4/79 (5.1%) 1/14 (7.1%) 5/93 (5.4%)
    Blood phosphorus increased 0/11 (0%) 4/79 (5.1%) 1/14 (7.1%) 5/93 (5.4%)
    Electrocardiogram QT prolonged 0/11 (0%) 4/79 (5.1%) 1/14 (7.1%) 5/93 (5.4%)
    Blood alkaline phosphatase increased 0/11 (0%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Blood phosphorus decreased 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Metabolism and nutrition disorders
    Hypokalaemia 1/11 (9.1%) 40/79 (50.6%) 7/14 (50%) 47/93 (50.5%)
    Hypophosphataemia 2/11 (18.2%) 28/79 (35.4%) 5/14 (35.7%) 33/93 (35.5%)
    Decreased appetite 1/11 (9.1%) 21/79 (26.6%) 3/14 (21.4%) 24/93 (25.8%)
    Hypomagnesaemia 0/11 (0%) 20/79 (25.3%) 4/14 (28.6%) 24/93 (25.8%)
    Hypocalcaemia 1/11 (9.1%) 14/79 (17.7%) 8/14 (57.1%) 22/93 (23.7%)
    Tumour lysis syndrome 0/11 (0%) 18/79 (22.8%) 3/14 (21.4%) 21/93 (22.6%)
    Hypoalbuminaemia 1/11 (9.1%) 13/79 (16.5%) 4/14 (28.6%) 17/93 (18.3%)
    Hyperglycaemia 1/11 (9.1%) 12/79 (15.2%) 3/14 (21.4%) 15/93 (16.1%)
    Hyperphosphataemia 0/11 (0%) 9/79 (11.4%) 0/14 (0%) 9/93 (9.7%)
    Hyponatraemia 0/11 (0%) 7/79 (8.9%) 1/14 (7.1%) 8/93 (8.6%)
    Hyperkalaemia 1/11 (9.1%) 5/79 (6.3%) 2/14 (14.3%) 7/93 (7.5%)
    Fluid overload 1/11 (9.1%) 6/79 (7.6%) 0/14 (0%) 6/93 (6.5%)
    Hypermagnesaemia 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Abnormal loss of weight 1/11 (9.1%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Fluid retention 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/11 (0%) 15/79 (19%) 1/14 (7.1%) 16/93 (17.2%)
    Arthralgia 1/11 (9.1%) 5/79 (6.3%) 1/14 (7.1%) 6/93 (6.5%)
    Muscular weakness 1/11 (9.1%) 5/79 (6.3%) 1/14 (7.1%) 6/93 (6.5%)
    Myalgia 1/11 (9.1%) 3/79 (3.8%) 0/14 (0%) 3/93 (3.2%)
    Pain in extremity 2/11 (18.2%) 3/79 (3.8%) 0/14 (0%) 3/93 (3.2%)
    Muscle spasms 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Coccydynia 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Intervertebral disc protrusion 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Pain in jaw 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Joint range of motion decreased 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Nervous system disorders
    Headache 2/11 (18.2%) 21/79 (26.6%) 2/14 (14.3%) 23/93 (24.7%)
    Dysgeusia 1/11 (9.1%) 8/79 (10.1%) 3/14 (21.4%) 11/93 (11.8%)
    Dizziness 1/11 (9.1%) 8/79 (10.1%) 2/14 (14.3%) 10/93 (10.8%)
    Syncope 1/11 (9.1%) 3/79 (3.8%) 1/14 (7.1%) 4/93 (4.3%)
    Somnolence 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Cerebrovascular accident 1/11 (9.1%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Hypoaesthesia 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Haemorrhage intracranial 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Psychiatric disorders
    Insomnia 1/11 (9.1%) 14/79 (17.7%) 3/14 (21.4%) 17/93 (18.3%)
    Anxiety 0/11 (0%) 6/79 (7.6%) 2/14 (14.3%) 8/93 (8.6%)
    Depression 1/11 (9.1%) 6/79 (7.6%) 0/14 (0%) 6/93 (6.5%)
    Abnormal dreams 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Hallucination 1/11 (9.1%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Completed suicide 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/11 (0%) 11/79 (13.9%) 2/14 (14.3%) 13/93 (14%)
    Haematuria 0/11 (0%) 6/79 (7.6%) 0/14 (0%) 6/93 (6.5%)
    Urinary retention 0/11 (0%) 2/79 (2.5%) 1/14 (7.1%) 3/93 (3.2%)
    Dysuria 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Renal failure 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Reproductive system and breast disorders
    Vaginal haemorrhage 1/11 (9.1%) 2/79 (2.5%) 0/14 (0%) 2/93 (2.2%)
    Acquired phimosis 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Testicular pain 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/11 (0%) 16/79 (20.3%) 2/14 (14.3%) 18/93 (19.4%)
    Dyspnoea 0/11 (0%) 10/79 (12.7%) 3/14 (21.4%) 13/93 (14%)
    Epistaxis 1/11 (9.1%) 10/79 (12.7%) 1/14 (7.1%) 11/93 (11.8%)
    Hypoxia 1/11 (9.1%) 5/79 (6.3%) 2/14 (14.3%) 7/93 (7.5%)
    Rhinorrhoea 0/11 (0%) 6/79 (7.6%) 1/14 (7.1%) 7/93 (7.5%)
    Oropharyngeal pain 0/11 (0%) 4/79 (5.1%) 2/14 (14.3%) 6/93 (6.5%)
    Pulmonary oedema 0/11 (0%) 4/79 (5.1%) 1/14 (7.1%) 5/93 (5.4%)
    Nasal congestion 0/11 (0%) 3/79 (3.8%) 1/14 (7.1%) 4/93 (4.3%)
    Pleuritic pain 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Rhinitis allergic 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Tachypnoea 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Chronic obstructive pulmonary disease 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Dysphonia 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Laryngeal inflammation 1/11 (9.1%) 1/79 (1.3%) 0/14 (0%) 1/93 (1.1%)
    Nasal discomfort 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 1/11 (9.1%) 10/79 (12.7%) 5/14 (35.7%) 15/93 (16.1%)
    Rash 1/11 (9.1%) 13/79 (16.5%) 1/14 (7.1%) 14/93 (15.1%)
    Dry skin 0/11 (0%) 9/79 (11.4%) 2/14 (14.3%) 11/93 (11.8%)
    Petechiae 0/11 (0%) 5/79 (6.3%) 1/14 (7.1%) 6/93 (6.5%)
    Pruritus 1/11 (9.1%) 6/79 (7.6%) 0/14 (0%) 6/93 (6.5%)
    Alopecia 0/11 (0%) 3/79 (3.8%) 1/14 (7.1%) 4/93 (4.3%)
    Erythema 0/11 (0%) 4/79 (5.1%) 0/14 (0%) 4/93 (4.3%)
    Drug eruption 0/11 (0%) 2/79 (2.5%) 1/14 (7.1%) 3/93 (3.2%)
    Night sweats 0/11 (0%) 2/79 (2.5%) 1/14 (7.1%) 3/93 (3.2%)
    Purpura 0/11 (0%) 2/79 (2.5%) 1/14 (7.1%) 3/93 (3.2%)
    Rash pruritic 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Dermatitis contact 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Papule 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Seborrhoeic dermatitis 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)
    Rash papular 1/11 (9.1%) 0/79 (0%) 0/14 (0%) 0/93 (0%)
    Vascular disorders
    Hypotension 2/11 (18.2%) 17/79 (21.5%) 5/14 (35.7%) 22/93 (23.7%)
    Hypertension 0/11 (0%) 9/79 (11.4%) 0/14 (0%) 9/93 (9.7%)
    Orthostatic hypotension 0/11 (0%) 4/79 (5.1%) 1/14 (7.1%) 5/93 (5.4%)
    Hot flush 0/11 (0%) 1/79 (1.3%) 1/14 (7.1%) 2/93 (2.2%)
    Embolism 0/11 (0%) 0/79 (0%) 1/14 (7.1%) 1/93 (1.1%)

    Limitations/Caveats

    The protocol underwent a few major amendments to shorten time to complete and allow for an expeditious analysis and reporting of outcomes. The study was terminated early Jan 2020 due to marked decrease in enrollment and thus could not reach all of its efficacy endpoints. Only select analyses could be performed. Treatment efficacy was summarized by distributing the safety population into 6 groups based on whether the patients received ACM or CM regimen and their disease stages at study entry.

    More Information

    Certain Agreements

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

    There is NOT 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 Susan Smith
    Organization Sumitomo Dainippon Pharma Oncology, Inc.
    Phone +1-210-414-7702
    Email Susan.smith@sdponcology.com
    Responsible Party:
    Sumitomo Pharma Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02520011
    Other Study ID Numbers:
    • TPI-ALV-201
    First Posted:
    Aug 11, 2015
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022