FILOCLL14 - STAIR : "Open-label, phase 2 study investigating the STop and restart Acalabrutinib In fRrail patients with previously untreated CLL (STAIR)"

Overview

Sponsor-declared trial summary

Key facts

Sponsor

French Innovative Leukemia Organization

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

12 Nov 2021 → ongoing

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513936-80-00

EudraCT number

2020-006081-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Others, Efficacy

To determine whether discontinuating ACA after 18 months in treatment-naïve CLL patients affects progression-free survival (PFS) at one year after treatment interruption.

Secondary objectives 4

1. Investigate the impact of ACA withdrawal on time to next treatment (TTNT) and overall survival (OS)
2. Investigate the Quality of life
3. Investigate the tolerance profile
4. Investigate the overall response rate to re-treatment with ACA after discontinuation in the experimental arm

Conditions and MedDRA coding

elderly patients (> 70 years) with CLL or SLL

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Age > 70 years or older
2. ECOG performance status ≤ 2
3. Previously untreated CLL or SLL
4. CLL or SLL requiring treatment according to the iwCLL 2018 criteria
5. Total CIRS score > 6 and / or 30 < CrCl < 69 mL/min
6. Both patients with or without TP53 disruption 17p deletion and/or TP53 mutations) can be included
7. Patients can be included whatever their IGHV mutational status
8. Patients with therapy-controlled cardiovascular comorbidities and/or anticoagulation (novel oral anticoagulant alone, aspirin alone, heparin alone) can be included (patients treated by vitamin K antagonist or dual anti-platelet therapy cannot be included)
9. Life expectancy > 6 months
10. Adequate hematology values: absolute neutrophil count ≥ 0.75 x 109/L, platelet count ≥ 50 x 109/L (accordance to the coordinator if linked to the disease)
11. Adequate liver function as indicated by a total bilirubin < 1.5, aspartate transaminase and alanine transaminase ≤ 3 the institutional upper limits of normal values, unless directly attributable to CLL, unless directly attributable to Gilbert’s syndrome
12. Signed (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including specify biology analysis, and are willing to participate in the study.

Exclusion criteria 13

1. Hypersensitivity to the active substance
2. Patients who are not vaccinated against COVID (2nd dose 15 days before inclusion)
3. Known HIV seropositivity
4. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: 1). Uncontrolled and/or active systemic infection (viral, bacterial or fungal). 2). Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus or hepatitis C virus infection, any uncontrolled active systemic infection along with subjects who are on ongoing anti-infective treatment and subjects who have received vaccination with a live attenuated vaccine within 4 weeks before the first dose of study treatment 2a). Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antibody (anti-HBs) negative will need to have a negative hepatitis B virus PCR result before enrollment. Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B virus PCR positive will be excluded. 2b). Subjects who are hepatitis C virus antibody positive will need to have a negative hepatitis C virus PCR result before enrollment. Those who are hepatitis C virus PCR positive will be excluded. 3). Active and uncontrolled autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) (isolated positive DAT is not an exclusion criteria) and idiopathic thrombocytopenic purpura (ITP). 4). Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.
5. Patients treated by vitamin K antagonist or dual anti-platelet therapy
6. History of bleeding diathesis (e.g. hemophilia or von Willebrand disease)
7. History of confirmed progressive multifocal leukoencephalopathy (PML).
8. Concurrent severe diseases which exclude the administration of therapy: 1). Heart insufficiency NYHA grade III/IV, LEVF < 50% and or RF < 30%, myocardial infarction within the past 6 months prior to study. 2). Significant cardiovascular disease such as symptomatic arrhythmias (including atrial fibrillation), congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional (Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study). 3). Severe chronic obstructive lung disease with hypoxemia. 4). History of stroke or intra-cranial hemorrhage within the last 6 months. 5). Severe diabetes mellitus. 6).Uncontrolled hypertension 7). Impaired renal function with creatinine clearance < 30 ml/min according the formula of Cockroft and Gault. 8). Patient who requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole) unless of separate dosing of acalabrutinib capsules with antacids by at least 2 hours. Acalabrutinib capsules should be taken 2 hours before an H2-receptor antagonist. Avoid co-administration of acalabrutinib capsules with proton pump inhibitors. 9). Disease significantly affecting gastrointestinal function (malabsorption syndrome, stomach or small bowel resection). 10). Evidence for Richter syndrome. 11). Treatment with any of the following within 7 days prior to the first dose of study drug : steroid therapy for anti-neoplastic intent. 12). A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect the patient’s participation in this study or interpretation of study outcomes. 13). Major surgery within 30 days prior to the first dose of study treatment. 14). History of prior other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following: - curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study; - other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which patient is disease-free for ≥ 5 years without further treatment
9. Adult under law-control
10. Fertile male patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study
11. No affiliation to social security
12. Patient under psychiatric care
13. Patient unable to express consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS at 1 year post-ACA discontinuation is defined as the time from randomization to progression (needing therapy or not) or death from any cause. Patients alive and progression-free will be censored at the last disease assessment or at initiation of next treatment. Progression will be evaluated using iwCLL 2018 criteria

Secondary endpoints 5

1. OS is defined as the time from randomization to death from any cause. Patients alive will be censored at last follow-up news.
2. TTNT is defined as the time from randomization to initiation of next treatment required for symptomatic CLL. Patients without initiation of next treatment will be censored at last follow-up date. This need for restarting therapy will be centrally validated by an independent board review and based on iwCLL 2018 criteria for symptomatic CLL.
3. QoL will be evaluated using the EORTC QLQ-C30 questionnaire
4. Secondary end point (English)
5. Overall Response Rate (ORR) to re-treatment is defined as the proportion of re-treated patients who achieved best response of complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) per iwCLL 2018 criteria.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

French Innovative Leukemia Organization

Sponsor organisation

French Innovative Leukemia Organization

Address

2 Boulevard Tonnelle

City

Tours

Postcode

37000

Country

France

Scientific contact point

Organisation

French Innovative Leukemia Organization

Contact name

Pr YSEBAERT Loïc

Public contact point

Organisation

French Innovative Leukemia Organization

Contact name

Secrétariat FILO

Third parties 8

Locations

1 EU/EEA country · 29 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 9 files

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

Application history

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