Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03263637
Other study ID # D8230C00001
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date October 24, 2017
Est. completion date September 30, 2021

Study information

Verified date October 2021
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Completed
Enrollment 44
Est. completion date September 30, 2021
Est. primary completion date September 30, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 130 Years
Eligibility Main Inclusion Criteria (cohorts 1, 2, 3): • Patients with histologically confirmed, relapsed or refractory haematological malignancies. Patients will include but are not limited to the following: Arm A : B-cell Non-Hodgkin lymphoma , T-cell Non-Hodgkin lymphoma , Small lymphocytic lymphoma (SLL) , Multiple myeloma (MM) Arm B: CLL (chronic lymphocytic leukaemia), Richter's syndrome , AML/secondary AML, ALL , High-risk myelodysplastic syndrome (MDS), CMML (chronic myelomonocytic leukemia) - Eastern Cooperative Oncology Group (ECOG) performance status of =2. - Must have received at least 2 prior lines of therapy - Documented active disease requiring treatment per respective NCCN/ESMO guideline that is relapsed or refractory defined as: Recurrence of disease after response to prior line(s) of therapy Or progressive disease after completion of the treatment regimen preceding entry into the study - Adequate hematologic, hepatic and renal function - Women should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test before start of dosing if of child-bearing potential or must have evidence of nonchildbearing potential - Men should be willing to use barrier contraception (ie, condoms) and refrain from sperm donation during and after the conduct of the trial. Main Exclusion Criteria (cohorts 1,2, 3): - Treatment with any of the following: any other chemotherapy, immunotherapy or anticancer agents within 2 weeks, any hematopoietic growth factors (e.g., filgrastim; [G-CSF] or sargramostin [GM-CSF]) within 7 days of the first dose of investigational product or pegylated G-CSF (pegfilgrastim) or darbepoetin within 14 days, any full-dose level anti-coagulation treatment sufficiently prior to treatment that INR is <1.5 (DVT/PE prophylaxis dose is allowed) or Major surgery (excluding placement of vascular access) within 4 weeks (with regard to the first dose of study treatment on this protocol). - With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment. - Presence of, or history of, CNS lymphoma, leptomeningeal disease or spinal cord compression. - History of prior nonhematologic malignancy with exceptions mentioned in protocol - Undergone any procedures or experienced any of the conditions listed in protocol exclusion criteria currently or in the preceding 6 months - Patients with any of the following: evidence of severe or uncontrolled systemic disease, asecretory myeloma, a known history of infection with human immunodeficiency virus (HIV), serological evidence of active Hepatitis B infection, cardiac abnormalities as mentioned in the protocol, previous allogeneic bone marrow transplant, adrenal gland insufficiency or pancreatitis. - History of severe allergic or anaphylactic reactions to BH3 mimetics or history of hypersensitivity to active or inactive excipients of AZD4573.

Study Design


Related Conditions & MeSH terms

  • Acute Lymphocytic Leukemia
  • Acute Myeloid Leukemia
  • B-cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
  • Chronic Myelomonocytic Leukemia
  • Hematologic Neoplasms
  • High Risk Myelodysplastic Syndrome
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, Myeloid, Acute
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Myelomonocytic, Juvenile
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Non-Hodgkin
  • Lymphoma, T-Cell
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Neoplasms
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Preleukemia
  • Relapsed or Refractory Haematological Malignancies Including
  • Richter's Syndrome
  • Small Lymphocytic Lymphoma
  • Syndrome
  • T-cell Non-Hodgkin Lymphoma

Intervention

Drug:
AZD4573
AZD4573 will be administered as a intravenous (IV) infusion.

Locations

Country Name City State
Germany Research Site Aachen
Germany Research Site Bonn
Germany Research Site Göttingen
Germany Research Site Heidelberg
Germany Research Site Ulm
Netherlands Research Site Amsterdam
Netherlands Research Site Nieuwegein
United Kingdom Research Site Cardiff
United Kingdom Research Site Manchester
United Kingdom Research Site Plymouth
United Kingdom Research Site Southampton
United Kingdom Research Site Sutton

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Countries where clinical trial is conducted

Germany,  Netherlands,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of adverse events Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters 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
Primary Dose limiting toxicities 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). 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
Primary Maximum tolerated dose After completion of dose limiting toxicity (DLT) period (8/4 weeks) for the maximum dose cohort
Secondary Maximum observed plasma concentration of AZD4573 The concentration of AZD4573 and its metabolites in blood will be determined (Cmax will be derived). 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)
Secondary Area under the concentration-time curve for plasma concentrations of AZD4573 The Area under the curve of AZD4573 and its metabolites in blood will be determined 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).
Secondary Volume of distribution (Vd). 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). 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).
Secondary Clearance (CL). 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. 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).
Secondary Antitumor activity of AZD4573 in patients by assessing overall response rate (ORR). 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 From time of first dose until discontinuation of AZD4573 expected to be for up to 12 months
Secondary Duration of response (DOR) 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 From time of first dose until disease progression expected to be for up to 12 months
Secondary Antitumor activity of AZD4573 in patients by assessing overall survival (OS). Proportion of patients alive at 12 months post treatment start or other defined timepoints From time of first dose until death or study end whatever is earlier expected to be for up to 12 months
Secondary Minimal Residual Disease (MRD) For applicable histologies/disease indications (e.g., CLL) using IWG criteria for response assessment every 4-12 weeks from start of treatment. From time of first dose until discontinuation of AZD4573 expected to be for up to 12 months
Secondary Progression free survival (PFS) 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 From time of first dose until first observation of progression expected to be for up to 12 months
See also
  Status Clinical Trial Phase
Recruiting NCT05027594 - Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02412878 - Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma Phase 3
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Recruiting NCT05971056 - Providing Cancer Care Closer to Home for Patients With Multiple Myeloma N/A
Recruiting NCT05243797 - Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation Phase 3
Active, not recruiting NCT04555551 - MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma Phase 1
Recruiting NCT05618041 - The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies N/A
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Recruiting NCT03570983 - A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT03665155 - First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody Phase 1/Phase 2
Completed NCT02812706 - Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients Phase 1/Phase 2
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Active, not recruiting NCT03989414 - A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM) Phase 1/Phase 2
Active, not recruiting NCT03792763 - Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients Phase 2
Withdrawn NCT03608501 - A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation Phase 2
Recruiting NCT04537442 - Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02546167 - CART-BCMA Cells for Multiple Myeloma Phase 1