Real World Outcomes Using Novel Agents for AML in the UK

Real World Outcomes Using Novel Agents for Acute Myeloid Leukaemia in the United Kingdom

This project will collect data on patients with acute myeloid leukemia in the United Kingdom who were treated with two new targeted therapies during the coronavirus pandemic

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Venetoclax; Drug: Gilteritinib

Detailed Description

Acute myeloid leukaemia (AML) is a blood cancer which in fit young adults is typically treated with intensive chemotherapy. While this is potentially curative, it is associated with significant side effects and the requirement for long hospital admissions. Infection is a major issue during AML treatment, as both the disease and the chemotherapy impair the immune system.

Early data suggested that COVID-19 is associated with a very high rate of death in AML patients undergoing intensive chemotherapy. Because of this, and the need for significant hospital resources to deliver intensive chemotherapy, the NHS made available two new, less intensive, targeted therapies for the treatment of AML during the COVID-19 pandemic - venetoclax and gilteritinib. The aim was to reduce mortality and healthcare resource use.

Many hundreds of patients across the UK have been treated with these two medications on the temporary access scheme. The research aims to collect de-identified data from treating patients to describe the outcomes of patients treated with these approaches, both in terms of the safety and effectiveness.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Richard Dillon; Phone Number: 020 7188 257; Email: richard.dillon@kcl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's and St Thomas' NHS Foundation Trust
    • Contact: Richard Dillon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The NHS criteria for access to venetoclax was that a patient was fit for IC and was:

• Aged >16y with NPM1 mutation without FLT3 internal tandem duplication (ITD)
• Aged >50y with NPM1, IDH1 or IDH2 mutations (regardless of FLT3 status)
• Patients aged >60y without favourable-risk cytogenetics

Gilteritinib was made available to all patients aged >16y with relapse or refractory FLT3 mutated AML. Other FLT3 inhibitors are available to patients through various access schemes

Description

Venetoclax cohort Inclusion criteria

1. Newly diagnosed acute myeloid leukaemia
2. No prior therapies for AML, apart from hydroxyurea (or similar) for cytoreduction. Previous treatments for MDS or other conditions are allowed
3. Treated with venetoclax in combination with either azacitidine or LDAC No exclusion criteria

Gilteritinib/FLT3 cohort Inclusion criteria

1. Relapsed acute myeloid leukaemia, including molecular relapse
2. Treated with FLT3 inhibitor No exclusion criteria

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Venetoclax; Venetoclax in newly diagnosed AML	Drug: Venetoclax; Observational study of venetoclax in AML; Other Names: Venclyxto
FLT3 inhibitors; FLT3 inhibitors including gilteritinib in relapsed AML	Drug: Gilteritinib; Observational study of gilteritinib in AML; Other Names: Xospata

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival measured from time of treatment initiation	1 year
Early death rate	Early death rate measured at day 60 after treatment initiation	Day 60 after starting treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Response rate as defined by ELN 2017	After 2 cycles of therapy (each cycle is 28 days although may be extended if recovery is delayed)
Incidence of relapse in patients achieving remission	Relapse incidence measured from the time of achieving remission	1 year
Relapse-free survival	RFS as defined by ELN	1 year
Treatment toxicity 1	Number of days in hospital and number of days of intensive care	During the first cycle of therapy (each cycle is 28 days although may be extended if recovery is delayed)
Treatment toxicity 2	Duration of neutropenia and thrombocytopenia	During the first cycle of therapy (each cycle is 28 days although may be extended if recovery is delayed)
Treatment toxicity 3	Number of blood and platelet transfusions	During the first cycle of therapy (each cycle is 28 days although may be extended if recovery is delayed)
Comparison of survival between patient sub-groups	Overall survival compared between disease groups	1 year

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: King's College London
• Investigators: Principal Investigator: Richard Dillon, King's College London

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: March 9, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: 305432 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No