Study to Assess Safety, Tolerability, Pharmacokinetics and Antitumor Activity of AZD4573 in Relapsed/Refractory Haematological Malignancies

Phase 1

Completed

• Conditions: High Risk Myelodysplastic Syndrome; T-cell Non-Hodgkin Lymphoma; Relapsed or Refractory Haematological Malignancies Including; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Chronic Myelomonocytic Leukemia; Richter's Syndrome; B-cell Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia
• Interventions: Drug: AZD4573

• Registration Number: NCT03263637
• Lead Sponsor: AstraZeneca

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-08-11
• Study First Submitted QC: 2017-08-24
• Study First Posted: 2017-08-28
• Study Start: 2017-10-24
• Primary Completion: 2021-09-30
• Study Completion: 2021-09-30
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-21
• Last Update Posted: 2021-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: (Cohort 1-3)	AZD4573	dose level 1-3 in subjects with relapsed or refractory haematological malignancies excluding AML/ALL/high-risk MDS/CMML/CLL.
Arm B: (Cohort 1-3)	AZD4573	dose level 1-3 in subjects with relapsed or refractory AML, ALL, high-risk MDS, CMML, CLL and Richter's syndrome.

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events	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	Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
Dose limiting toxicities	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	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).
Maximum tolerated dose	After completion of dose limiting toxicity (DLT) period (8/4 weeks) for the maximum dose cohort

Secondary Outcome Measures

Name	Time	Method
Maximum observed plasma concentration of AZD4573	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)	The concentration of AZD4573 and its metabolites in blood will be determined (Cmax will be derived).
Area under the concentration-time curve for plasma concentrations of AZD4573	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).	The Area under the curve of AZD4573 and its metabolites in blood will be determined
Volume of distribution (Vd).	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).	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).
Clearance (CL).	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).	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.
Antitumor activity of AZD4573 in patients by assessing overall response rate (ORR).	From time of first dose until discontinuation of AZD4573 expected to be for up to 12 months	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
Duration of response (DOR)	From time of first dose until disease progression expected to be for up to 12 months	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
Antitumor activity of AZD4573 in patients by assessing overall survival (OS).	From time of first dose until death or study end whatever is earlier expected to be for up to 12 months	Proportion of patients alive at 12 months post treatment start or other defined timepoints
Minimal Residual Disease (MRD)	From time of first dose until discontinuation of AZD4573 expected to be for up to 12 months	For applicable histologies/disease indications (e.g., CLL) using IWG criteria for response assessment every 4-12 weeks from start of treatment.
Progression free survival (PFS)	From time of first dose until first observation of progression expected to be for up to 12 months	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

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sutton, United Kingdom