MCLPhase 2ALTAMIRANCT05214183
Acalabrutinib and Rituximab in Elderly Patients With Untreated Mantle Cell Lymphoma
A Phase 2 study testing Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma in people with MCL and Mantle Cell Lymphoma, run by Nordic Lymphoma Group at 20 sites in 5 countries.
Trial summary
This is a phase II trial, with the aim of developing a chemotherapy-free regimen for untreated patients with mantle cell lymphoma (MCL). Acalabrutinib (ACP-196) is a next generation bruton tyrosine kinase (BTK) inhibitor, more selective than ibrutinib, and without in vitro antagonism of anti-CD20 directed… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- MCL, Mantle Cell Lymphoma
- What is being tested?
- Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 20 sitesin 5 countries
- Study dates
- 15 Dec 2021to Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥60 years
- Pathologically confirmed MCL (according to the 2016 WHO classification), with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1
- Stage II-IV, measurable by imaging and requiring treatment in the opinion of the treating clinician
- No previous treatment for MCL (other than localised radiotherapy or 7-day pulse of steroids for symptom control)
- ECOG performance status 0 - 2
- Absolute neutrophil count (ANC) > 1.0 x 109 and platelet count >100 x 109, unless related to lymphoma - in this situation, the threshold for inclusion is ANC > 0.5 x 109 and platelet count > 50 x 109
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- Creatinine clearance > 30 ml/min (Cockcroft-Gault)
- AST and/or ALT <3xULN and/or total bilirubin <3xULN
- Able to give voluntary written informed consent
- Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib or for 12 months after last dose of rituximab, whichever is longer
Who cannot join
- Patients considered fit enough to undergo autologous or allogeneic stem cell transplant for MCL
- Major surgery within two weeks prior to day 1 of cycle 1
- Patients who are unable to swallow capsules, or who have disease significantly affecting gastrointestinal function that would limit oral absorption of medication
- 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
- 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)
- Active infection requiring treatment
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- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Concurrent treatment with another investigational agent outside of this protocol
- Known history of drug-specific hypersensitivity or anaphylaxis to rituximab or acalabrutinib (including active product or excipient components).
- Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease)
- Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
- 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
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug
- Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN
- 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
- History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
- Breastfeeding or pregnant women
- Concurrent participation in another therapeutic clinical trial
- History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
- 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
- Received a live virus vaccination within 28 days of first dose of study drug
Trial locations and contacts
20 sites in 5 countries.
20 sites in 5 countries
Sweden11 sites
Hematological Department, Falu Hospital, Falun
Falun
Department of Hematology and Coagulation, Sahlgrenska University Hospital
Gothenburg
Department of Medicine, Halmstad Country Hospital
Halmstad
Department of Internal Medicine, Kalmar County Hospital
Kalmar
Hematologiska Kliniken, Universitetssjukhuset
Linköping
Department of Medicine, Sunderbyn Hospital
Luleå
Mats Jerkeman
Lund
Center of Hematology, Karolinska University Hospital
Stockholm
Uddevalla Hospital
Uddevalla
Cancercentrum, Norrlands Universitetsjukhus
Umeå
Department of Oncology, Uppsala Academic Hospital
Uppsala
Norway4 sites
Department of Oncology, Haukeland University Hospital
Bergen
Avd. for Kreftbehandling, Oslo Universitetssykehus
Oslo
Avdeling for Blod- og Kreftsykdommer, Stavanger Universitetssykehus
Stavanger
Kreftklinikken, St Olavs Hospital
Trondheim
Denmark2 sites
Department of Hematology X, Odense University Hospital
Odense
Department of Hematology, Zeeland University Hospital Roskilde
Roskilde
Finland2 sites
Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center
Helsinki
Oulu University Hospital
Oulu
South Korea1 site
Division of Hematology-Oncology Samsung Medical Center Seoul
Seoul
About this study
This is a phase II trial, with the aim of developing a chemotherapy-free regimen for untreated patients with mantle cell lymphoma (MCL).
Acalabrutinib (ACP-196) is a next generation bruton tyrosine kinase (BTK) inhibitor, more selective than ibrutinib, and without in vitro antagonism of anti-CD20 directed immunotherapies, indicating that its combination with rituximab may be more active than the combination of ibrutinib and rituximab.
Read more
In this trial proposal, we will also assess the activity of this combination in comparison to a historical control of ibrutinib + rituximab, consisting of the experimental arm of ibrutinib + rituximab in the randomized ENRICH trial (EudraCT number 2015-000832-13), and data from our previous trial with R-bendamustine-lenalidomide (NLG-MCL4).
The duration of treatment will be a minimum of 12 months. Patients in molecular remission in blood and bone marrow and in complete remission according to CT, will then stop acalabrutinib, but continue on rituximab for a maximum of 36 months. Patients that are minimal residual disease positive (MRD+) will be evaluated again every 6 months and continue on acalabrutinib for a maximum of 36 months.
Patients without a molecular marker, that cannot be followed with MRD, will stop treatment if in CR with PET at 12 months, and be followed by PET-CT every 6 months for a maximum of 36 months.
Patients who convert back to MRD positive after stopping acalabrutinib are reinstalled on acalabrutinib until progression.
Patients with TP53 aberrations and/or blastoid histology, will monitor MRD but continue with treatment until progression regardless of MRD results.
A planned interim analysis will be performed when 40 patients have undergone response assessment after 6 months, for futility and efficacy.
If less than 16 of 40 patients obtain a CR, the trial will be stopped due to futility.
- Conditions
- MCL, Mantle Cell Lymphoma
- Being tested
- Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma
- Medical subject headings
- Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acalabrutinib-rituximab in patients with untreated mantle cell lymphomaDrug
Acalabrutinib, or ACP-196, is a next generation BTK inhibitor, more selective than ibrutinib, and without in vitro antagonism of anti-CD20 directed immunotherapies, indicating that its combination with rituximab may be more active than the combination of ibrutinib and rituximab
| Study group | Role | What they receive |
|---|---|---|
| Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma | Experimental | Not described Receives: Drug: Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
The primary efficacy endpoint is progression-free survival, compared to the MCL4 data by log rank test
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2022
- Study start15 Dec 2021
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MCLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nordic Lymphoma Group
- Sponsor type
- Research network
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Mats Jerkeman, Principal investigator, Department of Oncology, Skåne University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05214183
- Sponsor's protocol ID
- NLG-MCL8 ALTAMIRA
- Acronym
- ALTAMIRA
- Status last verified
- Feb 2024
- First submitted
- 20 Oct 2021
- Last updated
- 12 Feb 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acalabrutinib and Rituximab in Elderly Patients With Untreated Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT05214183
- Acronym / sponsor ID
- ALTAMIRA / NLG-MCL8 ALTAMIRA
- Conditions
- MCL, Mantle Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Nordic Lymphoma GroupResearch network
- Collaborators
- AstraZeneca
- Study start
- 15 Dec 2021 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 28 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II trial, with the aim of developing a chemotherapy-free regimen for untreated patients with mantle cell lymphoma (MCL).
Acalabrutinib (ACP-196) is a next generation bruton tyrosine kinase (BTK) inhibitor, more selective than ibrutinib, and without in vitro antagonism of anti-CD20 directed immunotherapies, indicating that its combination with rituximab may be more active than the combination of ibrutinib and rituximab.
In this trial proposal, we will also assess the activity of this combination in comparison to a historical control of ibrutinib + rituximab, consisting of the experimental arm of ibrutinib + rituximab in the randomized ENRICH trial (EudraCT number 2015-000832-13), and data from our previous trial with R-bendamustine-lenalidomide (NLG-MCL4).
The duration of treatment will be a minimum of 12 months. Patients in molecular remission in blood and bone marrow and in complete remission according to CT, will then stop acalabrutinib, but continue on rituximab for a maximum of 36 months. Patients that are minimal residual disease positive (MRD+) will be evaluated again every 6 months and continue on acalabrutinib for a maximum of 36 months.
Patients without a molecular marker, that cannot be followed with MRD, will stop treatment if in CR with PET at 12 months, and be followed by PET-CT every 6 months for a maximum of 36 months.
Patients who convert back to MRD positive after stopping acalabrutinib are reinstalled on acalabrutinib until progression.
Patients with TP53 aberrations and/or blastoid histology, will monitor MRD but continue with treatment until progression regardless of MRD results.
A planned interim analysis will be performed when 40 patients have undergone response assessment after 6 months, for futility and efficacy.
If less than 16 of 40 patients obtain a CR, the trial will be stopped due to futility.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma | Experimental | Drug: Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥60 years
- Pathologically confirmed MCL (according to the 2016 WHO classification), with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1
- Stage II-IV, measurable by imaging and requiring treatment in the opinion of the treating clinician
- No previous treatment for MCL (other than localised radiotherapy or 7-day pulse of steroids for symptom control)
- ECOG performance status 0 - 2
Key exclusion criteria (21 listed)
- Patients considered fit enough to undergo autologous or allogeneic stem cell transplant for MCL
- Major surgery within two weeks prior to day 1 of cycle 1
- Patients who are unable to swallow capsules, or who have disease significantly affecting gastrointestinal function that would limit oral absorption of medication
- 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
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acalabrutinib-rituximab in patients with untreated mantle cell lymphomaAcalabrutinib, or ACP-196, is a next generation BTK inhibitor, more selective than ibrutinib, and without in vitro antagonism of anti-CD20 directed immunotherapies, indicating that its combination with rituximab may be more active than the combination of ibrutinib and rituximab | Drug | Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma |
Primary outcome
Progression-free survival
Time frame: 5 years
The primary efficacy endpoint is progression-free survival, compared to the MCL4 data by log rank test
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2024.
Related trials for MCL
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Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
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RecruitingPhase 3
A Trial to Learn How Well Linvoseltamab Works Compared to the Combination of Elotuzumab, Pomalidomide and Dexamethasone for Adult Participants With Relapsed/Refractory Multiple Myeloma
Relapsed Refractory Multiple Myeloma (RRMM)
RecruitingPhase 3
A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
Lymphoma
Active, not recruitingPhase 1/2
First-in-Human (FIH) Trial in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
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RecruitingObservational study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mats Jerkeman principal investigator
Department of Oncology, Skåne University Hospital
20 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma in people with MCL and Mantle Cell Lymphoma, run by Nordic Lymphoma Group at 20 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Sweden, Norway, Denmark, Finland, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2024.