Acalabrutinib and rituximab in elderly patients with untreated mantle cell lymphoma (ALTAMIRA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane

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

7 Dec 2021 → ongoing

Decision date (initial)

2024-09-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509864-96-00

EudraCT number

2018-001850-80

ClinicalTrials.gov

NCT05214183

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To evaluate progression-free survival with acalabrutinib-rituximab in patients with untreated mantle cell lymphoma, compared to data from the NLG-MCL4 trial.

Secondary objectives 9

1. Complete response rate
2. Molecular remission rate (MRR) by PCR
3. Overall response rate
4. Progression-free survival
5. Response duration
6. Duration of molecular remission
7. Overall survival
8. Safety
9. CR, MRR and ORR in TP53-mutated MCL

Conditions and MedDRA coding

Mantle Cell Lymphoma (MCL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Age ≥60 years
2. Pathologically confirmed MCL (according to the WHO 2016 classification), with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1
3. Stage II-IV, measurable by imaging and requiring treatment in the opinion of the treating clinician
4. No previous treatment for MCL (other than localised radiotherapy or 7-day pulse of steroids for symptom control)
5. ECOG performance status 0 – 2
6. Absolute neutrophil count (ANC) > 1.0 x 10^9 and platelet count > 100 x 10^9, unless related to lymphoma - in this situation, the threshold for inclusion is ANC >0.5 x 10^9 and platelet count > 50 x 10^9
7. Creatinine clearance >30 ml/min (Cockcroft-Gault)
8. AST and/or ALT <3x ULN and/or P-bilirubin <3x ULN
9. Able to give voluntary written informed consent
10. Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception (see appendix 2) during treatment and for 2 days after the last dose of acalabrutinib or for 12 months after last dose of rituximab, whichever is longer

Exclusion criteria 21

1. Patients considered fit enough to undergo autologous or allogeneic stem cell transplant for MCL
2. Major surgery within two weeks prior to day 1 of cycle 1
3. Patients who are unable to swallow capsules/tablets, or who have disease significantly affecting gastrointestinal function that would limit oral absorption of medication
4. Known serological positivity for HBV, HCV, HIV. Patients who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Patients who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
5. Diagnosed with or treated for any other malignancy than MCL within 2 years prior to day 1 of cycle 1 (except basal cell carcinoma, cutaneous squamous cell carcinoma or any other in situ malignancy)
6. Active infection requiring treatment
7. Serious medical or psychiatric illness likely to interfere with participation in this clinical study
8. Concurrent treatment with another investigational agent outside of this protocol
9. Known history of drug-specific hypersensitivity or anaphylaxis to rituximab or acalabrutinib (including active product or excipient components)
10. Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease)
11. Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
12. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited
13. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
14. Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN.
15. Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study
16. History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
17. Breastfeeding or pregnant women
18. Concurrent participation in another therapeutic clinical trial
19. History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
20. Significant cardiovascular disease such as symptomatic arrhythmias, 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 Classification at Screening. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study
21. Received a live virus vaccination within 28 days of first dose of study drug

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival. This is defined as the interval between date of obtaining informed consent and date of documented progression, first relapse, or death of any cause. Otherwise, patients will be censored at the last date they were known to be alive.

Secondary endpoints 9

1. Complete response rate at 6 months
2. Molecular remission rate (MRR) by PCR
3. Overall response rate
4. Progression-free survival (median)
5. Response duration (median)
6. Duration of molecular remission (median)
7. Overall survival (median)
8. CR, MRR and ORR in TP53-mutated MCL
9. Safety, in terms of all grade 3-5 AE

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Mats Jerkeman

Public contact point

Organisation

Region Skane

Contact name

Mats Jerkeman

Third parties 7

Locations

4 EU/EEA countries · 17 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 19 files

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

Application history

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