Study aimed at evaluating the efficacy of a combination treatment (decitabine and venetoclax) in patients with Acute Myeliode Leukemia who are ineligible or unresponsive to intensive chemotherapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Gimema Franco Mandelli Onlus

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

3 Dec 2021 → ongoing

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Srl · Fondazione GIMEMA Franco Mandelli onlus

External identifiers

EU CT number

2023-510241-16-00

EudraCT number

2020-006114-20

ClinicalTrials.gov

NCT04763928

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary objective of the trial is the efficacy of VEN-DEC regimen measured as event-free survival (EFS) in patients with AML secondary to MPN unfit for intensive chemotherapy.

Secondary objectives 2

1. Feasibility and safety of VEN-DEC regimen, as assessed by: 1-adverse events rate according to CTCAE criteria; 2-rate of death in aplasia; 3-days to neutrophil recovery and 4-days to platelet recovery after first and second cycle
2. Efficacy of VEN-DEC regimen as assessed by: 1- Rate of Acute leukemia responsecomplete (ALR-C) at first time-point (T1) after first cycle (ALR-C-T1); 2-Overall response rate after first cycle [Acute leukemia response-complete (ALR-C-T1) + Acute leukemia response-partial (ALR-P-T1)]; 3- Rate of Acute leukemia response-complete at second time-point (T2) after second cycle (ALR-C-T2); 4- Overall response rate after second cycle [Acute leukemia response complete (ALR-C-T2) + Acute leukemia responsepartial (ALR-P-T2)]; 5-Disease-free survival (DFS); 6-Overall survival (OS); 7- Cumulative incidence of relapse (CIR); 8- Treatment-related mortality (TRM); 9- Transfusion need (RBC and platelet) at 3 and 6 months of treatment

Conditions and MedDRA coding

Acute Myeloid Leukemia secondary to myeloproliferative neoplasms

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patients with AML secondary to myeloproliferative neoplasms (sAML), untreated, newly diagnosed, according to WHO 2016 criteria based on conventional cytological, cytogenetic and immunophenotypic disease characterization
2. Patients = 60 years or adult patients unfit for intensive treatment modalities at the discretion of the investigator.
3. ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care.
4. Signed written informed consent according to ICH/EU/GCP and national local laws.
5. Males enrolled in the study with partners who are women of childbearing potential, must be willing to use an acceptable barrier contraceptive method during the trial. Males should use contraception for 3 months after the last dose of decitabine. Females should use contraception for 1 month after the last dose of venetoclax or 6 months after the last dose of decitabine, whichever comes later.

Exclusion criteria 6

1. Diagnosis of de novo AML
2. Pre-existing, uncontrolled pathology such as heart failure (congestive/ischaemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), sever liver disease with total bilirubin >2,5 x ULN and/or ALT>3 ULN (unless attributable to AML), acute or chronic pancreatitis, kidney function impairment with Creatinine Clearance (CrCl) level <30ml/min (calculated by Cockcroft Gault formula)(unless attributable to AML) and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent or to cope with the intended treatment plan. For altered liver, pancreas and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
3. Pre-existing HIV positive serology (i.e. already known before enrolment). The participation to the study will require serology testing for HIV positivity at baseline: in case of HIV positivity or refusal to perform HIV testing, the patient will be considered not eligible.
4. Uncontrolled bacterial or fungal infections
5. QTc >470 msec on screening ECG (Fridericia's formula)
6. A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 6 months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is to evaluate the event free survival (EFS) at 1 year of an experimental VEN-DEC combination arm in patients with AML secondary to MPN and unfit for intensive therapeutic strategy. EFS is defined as the time between the date of treatment start and the date of either primary refractory disease (no achievement of at least ALR-C after 2 courses of treatment), first relapse (in patients who reached ALR-C) or death (whatever the cause), whichever occurs first.

Secondary endpoints 4

1. Feasibility and safety of VEN-DEC regimen, as assessed by: 1. Adverse events rate as per v5.0 CTCAE criteria 2. Rate of deaths in aplasia as per ELN 2017 definition 3. Days to neutrophils recovery after first and second cycle in responding patients 4. Days to platelets recovery after first and second cycle in responding patients
2. Efficacy of VEN-DEC regimen, as assessed by: 1. Response rate categorized as at least Acute leukemia response-complete at first time-point after first cycle (ALR-C-T1) 2. Overall response rate at first time-point after first cycle categorized as ALR-C-T1 + ALR-P-T1 as per post-MPN AML consortium definition 3. Response rate categorized as at least ALR-C at secondo time-point after second cycle (ALR-C-T2)
3. Efficacy of VEN-DEC regimen, as assessed by: 4. Overall response rate after second cycle categorized as ALR-C-T2 + ALR-P-T2 as per post-MPN AML consortium definition 5. Disease-free survival (DFS) as per ELN 2017 definition 6. Overall survival (OS) as per ELN 2017 definition 7. Cumulative incidence of relapse (CIR)
4. Efficacy of VEN-DEC regimen, as assessed by: 8. Treatment-related mortality (TRM) 9. Transfusion need as defined as number of RBC and platelet units transfused over a period of 3 and 6 months of treatment as per institutional thresholds for transfusion support in hematological neoplasms.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Gimema Franco Mandelli Onlus

Sponsor organisation

Fondazione Gimema Franco Mandelli Onlus

Address

Via Casilina 5

City

Rome

Postcode

00182

Country

Italy

Scientific contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

Centro Dati GIMEMA

Public contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

Centro Dati GIMEMA

Third parties 1

Locations

1 EU/EEA country · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications