VEN-R DASA-IPC 2022-067 Evaluation of DASATINIB monotherapy efficacy in acute myeloid leukemia patients refractory to VENETOCLAX-AZACITIDINE

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Paoli-Calmettes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Apr 2024 → ongoing

Decision date (initial)

2023-12-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French ministry of health, DGOS

External identifiers

EU CT number

2023-505846-24-00

WHO UTN

U1111-1292-4934

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The main objective is to assess the tumor response after 2 cycles of DASATINIB monotherapy treatment for patients with chemotherapy-ineligible acute myeloid leukemia refractory to VEN-AZA therapy.

Secondary objectives 1

1. The secondary objectives are to assess the efficacy and tolerance of DASATINIB monotherapy treatment for patients with acute myeloid leukemia refractory to VENETOCLAX-AZACITIDINE therapy and to identify clinical and biological predictive factors of response to DASATINIB therapy.

Conditions and MedDRA coding

acute myeloid leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Confirmed diagnosis of AML except Philadelphia chromosome-positive AML (Ph+) and acute promyelocytic leukemia (AML M3)
2. Age ≥ 18 years
3. ECOG ≤3
4. VEN-AZA refractory defined as no response after two cycles of VEN-AZA whatever the dose and the treatment duration
5. Signed informed consent form
6. Affiliation to a social security system, or beneficiary of such a system

Exclusion criteria 12

1. Central nervous system involvement
2. Patient under a legal protection measure (adult under guardianship, curatorship or safeguard of justice)
3. Inability to undergo the clinical trial medical follow-up for geographical, social or psychological reasons
4. Heart failure defined as one of the following criteria: a. Stage III or IV heart failure according to the New York Heart Association Classification including pre-existing clinically significant arrhythmia, congestive heart failure or cardiomyopathy. b. Angina pectoris ≤ 3 months before the start of the experimental treatment. c. Acute myocardial infarction ≤ 3 months before the start of the experimental treatment. d. Other clinically significant heart disease (e.g. uncontrolled hypertension, history of labile hypertension or history of poor adherence with an antihypertensive medication). e. Left ventricle ejection fraction < 50 %.
5. Liver failure defined as: a. Liver enzymes: ALT and/or AST ≤ 2.5 of upper limit of normal except if the increased ALT/AST levels are related to AML. b. Total bilirubin ≤ 3 x the upper limit of normal except in case of Gilbert’s syndrome.
6. Kidney failure defined as creatinine clearance ≥45 ml/min (estimated by the diet in the renal disease equation or measured by using a 24-hour urine collection).
7. Contraindication to DASATINIB: a. Patients with a congenital long QT syndrome, patients treated with antiarrhythmic drugs or other medications that may cause long QT syndrome. b. Current therapy using strong inhibitors of CYP3A4 (ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir, telithromycin, grapefruit juice). c. Patients with rare hereditary fructose intolerance, glucose-lactose malabsorption or sucrase-isomaltase deficiency.
8. Positive for HIV, Hepatitis B or C
9. Pregnant or breastfeeding woman
10. No efficient contraception for the women of childbearing age
11. Emergency situation person or not able to express his/her informed consent
12. Patient eligible to a targeted therapy having a market authorization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate after 2 cycles of 28 days DASATINIB defined as the rate of complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) according to ELN 2022 criteria.

Secondary endpoints 7

1. Different response rates (RC, CRi, or partial remission (PR)) according to ELN 2022 criteria.
2. Blast clearance rate (morphologic leukemia free state, MLFS) according to ELN 2022 criteria
3. Time to response (time between the start of the treatment until achievement of the CR, CRi or PR)
4. Duration of relapse-free period (time between the response time and the relapse)
5. Event-free survival (EFS, time between start of treatment and relapse, no reponse or death)
6. Overall survival (duration of survival from the start of the treatment)
7. Occurrence of Adverse Events according to CTCAE v5.0 and Serious Adverse Reaction

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Paoli-Calmettes

Sponsor organisation

Institut Paoli-Calmettes

Address

232 Boulevard De Sainte Marguerite, Bp 156 Bp 156

City

Marseille

Postcode

13009

Country

France

Scientific contact point

Organisation

Institut Paoli-Calmettes

Contact name

GARCIAZ Sylvain

Public contact point

Organisation

Institut Paoli-Calmettes

Contact name

LAROSA Marina

Third parties 2

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Application history

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