<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03263637</url>
  </required_header>
  <id_info>
    <org_study_id>D8230C00001</org_study_id>
    <nct_id>NCT03263637</nct_id>
  </id_info>
  <brief_title>Study to Assess Safety, Tolerability, Pharmacokinetics and Antitumor Activity of AZD4573 in Relapsed/Refractory Haematological Malignancies</brief_title>
  <official_title>A Phase 1, Open-Label, Multicentre, Non-Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of AZD4573, a Potent and Selective CDK9 Inhibitor, in Subjects With Relapsed or Refractory Haematological Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK),&#xD;
      pharmacodynamics (PD) and preliminary antitumor activity of AZD4573 in subjects with relapsed&#xD;
      or refractory haematological malignancies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 24, 2017</start_date>
  <completion_date type="Actual">September 30, 2021</completion_date>
  <primary_completion_date type="Actual">September 30, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This study is a multicentre, open-label, first in human, non-randomized, dose-escalation study including an intra-subject ramp-up. The study will consist of two, parallel dose escalation arms</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>At every treatment and follow up visit from the time of informed consent up to 8 months initially or if clinical benefit continues, until disease progression. Expected to be for 12 months</time_frame>
    <description>Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose limiting toxicities</measure>
    <time_frame>From day 1 of first cycle for a period of 8 weeks for cohorts 1 and 2, and for a period of 4 weeks for cohort 3 and for any other subsequent cohort that may be opened</time_frame>
    <description>DLTs will be determined from monitoring adverse events (AEs), and abnormal laboratory tests (clinical chemistry, hematology, and urinalysis), physical examinations, vital signs (blood pressure and pulse), and electrocardiogram (ECG).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerated dose</measure>
    <time_frame>After completion of dose limiting toxicity (DLT) period (8/4 weeks) for the maximum dose cohort</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma concentration of AZD4573</measure>
    <time_frame>For Cohorts 1 and 2: Over 8 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1). For Cohort 3: Over 4 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1)</time_frame>
    <description>The concentration of AZD4573 and its metabolites in blood will be determined (Cmax will be derived).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve for plasma concentrations of AZD4573</measure>
    <time_frame>For Cohorts 1 and 2: Over 8 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1). For Cohort 3: Over 4 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1).</time_frame>
    <description>The Area under the curve of AZD4573 and its metabolites in blood will be determined</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution (Vd).</measure>
    <time_frame>For Cohorts 1 and 2: Over 8 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1). For Cohort 3: Over 4 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1).</time_frame>
    <description>The concentration of AZD4573 and its metabolites in blood will be determined. Volume of distribution (Vd) is the apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration to drug amount in the body).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL).</measure>
    <time_frame>For Cohorts 1 and 2: Over 8 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1). For Cohort 3: Over 4 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1).</time_frame>
    <description>The concentration of AZD4573 and its co-former in blood will be determined. Clearance (CL) is the volume of plasma cleared of the drug per unit time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antitumor activity of AZD4573 in patients by assessing overall response rate (ORR).</measure>
    <time_frame>From time of first dose until discontinuation of AZD4573 expected to be for up to 12 months</time_frame>
    <description>To assess proportion of patients with anti tumor response to AZD4573. response assessment by Cheson (2014) criteria for for NHL, SLL, T-cell lymphoma and Richter syndrome, IWG criteria for CLL (Hallek 2008) and myeloma (Palumbo 2014), AML response criteria for AML (Doner 2010), SWOG (2016) criteria for ALL and MDS and CMML by IWG (Savona 2015) .Response will be evaluated every 4-12 weeks (based on disease type) until progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>From time of first dose until disease progression expected to be for up to 12 months</time_frame>
    <description>To assess the duration of anti tumor activity of AZD4573. To assess the progression free survival of AZD4573. response assessment by Cheson (2014) criteria for for NHL, SLL, T-cell lymphoma and Richter syndrome, IWG criteria for CLL (Hallek 2008) and myeloma (Palumbo 2014), AML response criteria for AML (Doner 2010), SWOG (2016) criteria for ALL and MDS and CMML by IWG (Savona 2015) . Response will be evaluated every 4-12 weeks (based on disease type) until progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antitumor activity of AZD4573 in patients by assessing overall survival (OS).</measure>
    <time_frame>From time of first dose until death or study end whatever is earlier expected to be for up to 12 months</time_frame>
    <description>Proportion of patients alive at 12 months post treatment start or other defined timepoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal Residual Disease (MRD)</measure>
    <time_frame>From time of first dose until discontinuation of AZD4573 expected to be for up to 12 months</time_frame>
    <description>For applicable histologies/disease indications (e.g., CLL) using IWG criteria for response assessment every 4-12 weeks from start of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>From time of first dose until first observation of progression expected to be for up to 12 months</time_frame>
    <description>To assess the progression free survival of AZD4573. response assessment by Cheson (2014) criteria for for NHL, SLL, T-cell lymphoma and Richter syndrome, IWG criteria for CLL (Hallek 2008) and myeloma (Palumbo 2014), AML response criteria for AML (Doner 2010), SWOG (2016) criteria for ALL and MDS and CMML by IWG (Savona 2015) . Response will be evaluated every 4-12 weeks (based on disease type) until progression</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Relapsed or Refractory Haematological Malignancies Including</condition>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Acute Lymphocytic Leukemia</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>High Risk Myelodysplastic Syndrome</condition>
  <condition>Chronic Myelomonocytic Leukemia</condition>
  <condition>Richter's Syndrome</condition>
  <condition>B-cell Non-Hodgkin Lymphoma</condition>
  <condition>T-cell Non-Hodgkin Lymphoma</condition>
  <condition>Small Lymphocytic Lymphoma</condition>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Arm A: (Cohort 1-3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dose level 1-3 in subjects with relapsed or refractory haematological malignancies excluding AML/ALL/high-risk MDS/CMML/CLL.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: (Cohort 1-3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>dose level 1-3 in subjects with relapsed or refractory AML, ALL, high-risk MDS, CMML, CLL and Richter's syndrome.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AZD4573</intervention_name>
    <description>AZD4573 will be administered as a intravenous (IV) infusion.</description>
    <arm_group_label>Arm A: (Cohort 1-3)</arm_group_label>
    <arm_group_label>Arm B: (Cohort 1-3)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria (cohorts 1, 2, 3):&#xD;
&#xD;
        • Patients with histologically confirmed, relapsed or refractory haematological&#xD;
        malignancies. Patients will include but are not limited to the following: Arm A : B-cell&#xD;
        Non-Hodgkin lymphoma , T-cell Non-Hodgkin lymphoma , Small lymphocytic lymphoma (SLL) ,&#xD;
        Multiple myeloma (MM) Arm B: CLL (chronic lymphocytic leukaemia), Richter's syndrome ,&#xD;
        AML/secondary AML, ALL , High-risk myelodysplastic syndrome (MDS), CMML (chronic&#xD;
        myelomonocytic leukemia)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.&#xD;
&#xD;
          -  Must have received at least 2 prior lines of therapy&#xD;
&#xD;
          -  Documented active disease requiring treatment per respective NCCN/ESMO guideline that&#xD;
             is relapsed or refractory defined as: Recurrence of disease after response to prior&#xD;
             line(s) of therapy Or progressive disease after completion of the treatment regimen&#xD;
             preceding entry into the study&#xD;
&#xD;
          -  Adequate hematologic, hepatic and renal function&#xD;
&#xD;
          -  Women should be using adequate contraceptive measures, should not be breast feeding&#xD;
             and must have a negative pregnancy test before start of dosing if of child-bearing&#xD;
             potential or must have evidence of nonchildbearing potential&#xD;
&#xD;
          -  Men should be willing to use barrier contraception (ie, condoms) and refrain from&#xD;
             sperm donation during and after the conduct of the trial.&#xD;
&#xD;
        Main Exclusion Criteria (cohorts 1,2, 3):&#xD;
&#xD;
          -  Treatment with any of the following: any other chemotherapy, immunotherapy or&#xD;
             anticancer agents within 2 weeks, any hematopoietic growth factors (e.g., filgrastim;&#xD;
             [G-CSF] or sargramostin [GM-CSF]) within 7 days of the first dose of investigational&#xD;
             product or pegylated G-CSF (pegfilgrastim) or darbepoetin within 14 days, any&#xD;
             full-dose level anti-coagulation treatment sufficiently prior to treatment that INR is&#xD;
             &lt;1.5 (DVT/PE prophylaxis dose is allowed) or Major surgery (excluding placement of&#xD;
             vascular access) within 4 weeks (with regard to the first dose of study treatment on&#xD;
             this protocol).&#xD;
&#xD;
          -  With the exception of alopecia, any unresolved toxicities from prior therapy greater&#xD;
             than CTCAE Grade 1 at the time of starting study treatment.&#xD;
&#xD;
          -  Presence of, or history of, CNS lymphoma, leptomeningeal disease or spinal cord&#xD;
             compression.&#xD;
&#xD;
          -  History of prior nonhematologic malignancy with exceptions mentioned in protocol&#xD;
&#xD;
          -  Undergone any procedures or experienced any of the conditions listed in protocol&#xD;
             exclusion criteria currently or in the preceding 6 months&#xD;
&#xD;
          -  Patients with any of the following: evidence of severe or uncontrolled systemic&#xD;
             disease, asecretory myeloma, a known history of infection with human immunodeficiency&#xD;
             virus (HIV), serological evidence of active Hepatitis B infection, cardiac&#xD;
             abnormalities as mentioned in the protocol, previous allogeneic bone marrow&#xD;
             transplant, adrenal gland insufficiency or pancreatitis.&#xD;
&#xD;
          -  History of severe allergic or anaphylactic reactions to BH3 mimetics or history of&#xD;
             hypersensitivity to active or inactive excipients of AZD4573.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>130 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Aachen</city>
        <zip>52074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bonn</city>
        <zip>53127</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Göttingen</city>
        <zip>37075</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105 AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nieuwegein</city>
        <zip>3435 CM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Cardiff</city>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Plymouth</city>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Southampton</city>
        <zip>S016 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sutton</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Netherlands</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Poland</country>
  </removed_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>October 21, 2021</last_update_submitted>
  <last_update_submitted_qc>October 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Relapsed or refractory haematological malignancies</keyword>
  <keyword>AZD4573</keyword>
  <keyword>CDK9i</keyword>
  <keyword>Acute Myeloid Leukemia (AML)</keyword>
  <keyword>Acute Lymphocytic Leukemia (ALL)</keyword>
  <keyword>Chronic lymphocytic Leukemia (CLL)</keyword>
  <keyword>High risk Myelodysplastic syndrome (MDS)</keyword>
  <keyword>Chronic Myelomonocytic Leukemia (CML)</keyword>
  <keyword>Richter's syndrome</keyword>
  <keyword>B-cell Non-Hodgkin Lymphoma (B-cell NHL)</keyword>
  <keyword>T-cell Non-Hodgkin Lymphoma (T-cell NHL)</keyword>
  <keyword>Small lymphocytic Lymphoma (SLL)</keyword>
  <keyword>Multiple Myeloma (MM)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Preleukemia</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Chronic</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Leukemia, Myelomonocytic, Juvenile</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_description>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
    <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03263637
org study id: D8230C00001
nct id: NCT03263637
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK),
      pharmacodynamics (PD) and preliminary antitumor activity of AZD4573 in subjects with relapsed
      or refractory haematological malignancies.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: This study is a multicentre, open-label, first in human, non-randomized, dose-escalation study including an intra-subject ramp-up. The study will consist of two, parallel dose escalation arms
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of adverse events
time frame: At every treatment and follow up visit from the time of informed consent up to 8 months initially or if clinical benefit continues, until disease progression. Expected to be for 12 months
description: Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
measure: Dose limiting toxicities
time frame: From day 1 of first cycle for a period of 8 weeks for cohorts 1 and 2, and for a period of 4 weeks for cohort 3 and for any other subsequent cohort that may be opened
description: DLTs will be determined from monitoring adverse events (AEs), and abnormal laboratory tests (clinical chemistry, hematology, and urinalysis), physical examinations, vital signs (blood pressure and pulse), and electrocardiogram (ECG).
measure: Maximum tolerated dose
time frame: After completion of dose limiting toxicity (DLT) period (8/4 weeks) for the maximum dose cohort
measure: Maximum observed plasma concentration of AZD4573
time frame: For Cohorts 1 and 2: Over 8 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1). For Cohort 3: Over 4 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1)
description: The concentration of AZD4573 and its metabolites in blood will be determined (Cmax will be derived).
measure: Area under the concentration-time curve for plasma concentrations of AZD4573
time frame: For Cohorts 1 and 2: Over 8 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1). For Cohort 3: Over 4 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1).
description: The Area under the curve of AZD4573 and its metabolites in blood will be determined
measure: Volume of distribution (Vd).
time frame: For Cohorts 1 and 2: Over 8 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1). For Cohort 3: Over 4 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1).
description: The concentration of AZD4573 and its metabolites in blood will be determined. Volume of distribution (Vd) is the apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration to drug amount in the body).
measure: Clearance (CL).
time frame: For Cohorts 1 and 2: Over 8 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1). For Cohort 3: Over 4 weeks (from dosing Day 1 of ramp-up Cycle A until Day 1 of the target dose Cycle 1).
description: The concentration of AZD4573 and its co-former in blood will be determined. Clearance (CL) is the volume of plasma cleared of the drug per unit time.
measure: Antitumor activity of AZD4573 in patients by assessing overall response rate (ORR).
time frame: From time of first dose until discontinuation of AZD4573 expected to be for up to 12 months
description: To assess proportion of patients with anti tumor response to AZD4573. response assessment by Cheson (2014) criteria for for NHL, SLL, T-cell lymphoma and Richter syndrome, IWG criteria for CLL (Hallek 2008) and myeloma (Palumbo 2014), AML response criteria for AML (Doner 2010), SWOG (2016) criteria for ALL and MDS and CMML by IWG (Savona 2015) .Response will be evaluated every 4-12 weeks (based on disease type) until progression
measure: Duration of response (DOR)
time frame: From time of first dose until disease progression expected to be for up to 12 months
description: To assess the duration of anti tumor activity of AZD4573. To assess the progression free survival of AZD4573. response assessment by Cheson (2014) criteria for for NHL, SLL, T-cell lymphoma and Richter syndrome, IWG criteria for CLL (Hallek 2008) and myeloma (Palumbo 2014), AML response criteria for AML (Doner 2010), SWOG (2016) criteria for ALL and MDS and CMML by IWG (Savona 2015) . Response will be evaluated every 4-12 weeks (based on disease type) until progression
measure: Antitumor activity of AZD4573 in patients by assessing overall survival (OS).
time frame: From time of first dose until death or study end whatever is earlier expected to be for up to 12 months
description: Proportion of patients alive at 12 months post treatment start or other defined timepoints
measure: Minimal Residual Disease (MRD)
time frame: From time of first dose until discontinuation of AZD4573 expected to be for up to 12 months
description: For applicable histologies/disease indications (e.g., CLL) using IWG criteria for response assessment every 4-12 weeks from start of treatment.
measure: Progression free survival (PFS)
time frame: From time of first dose until first observation of progression expected to be for up to 12 months
description: To assess the progression free survival of AZD4573. response assessment by Cheson (2014) criteria for for NHL, SLL, T-cell lymphoma and Richter syndrome, IWG criteria for CLL (Hallek 2008) and myeloma (Palumbo 2014), AML response criteria for AML (Doner 2010), SWOG (2016) criteria for ALL and MDS and CMML by IWG (Savona 2015) . Response will be evaluated every 4-12 weeks (based on disease type) until progression
arm group label: Arm A: (Cohort 1-3)
arm group type: Experimental
description: dose level 1-3 in subjects with relapsed or refractory haematological malignancies excluding AML/ALL/high-risk MDS/CMML/CLL.
arm group label: Arm B: (Cohort 1-3)
arm group type: Experimental
description: dose level 1-3 in subjects with relapsed or refractory AML, ALL, high-risk MDS, CMML, CLL and Richter's syndrome.
intervention type: Drug
intervention name: AZD4573
description: AZD4573 will be administered as a intravenous (IV) infusion.
arm group label: Arm A: (Cohort 1-3)
arm group label: Arm B: (Cohort 1-3)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 130 Years
healthy volunteers: No
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country: Germany
country: Netherlands
country: United Kingdom
country: Poland
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Multiple Myeloma
mesh term: Neoplasms
mesh term: Lymphoma, Non-Hodgkin
mesh term: Preleukemia
mesh term: Leukemia, Lymphoid
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Leukemia, Myelomonocytic, Chronic
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, T-Cell
mesh term: Leukemia, Myelomonocytic, Juvenile
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Hematologic Neoplasms
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd access criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home