Acalabrutinib and Rituximab in Elderly Patients With Untreated Mantle Cell Lymphoma

NCT05214183 | Active Not Recruiting Phase 2

• 1 other identifier: NLG-MCL8 ALTAMIRA
• Study Type: interventional
• Target: 81
• Locations: 5 countries
• Sites: 20

Brief 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 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.

Conditions

MCL; Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  The primary efficacy endpoint is progression-free survival, compared to the MCL4 data by log rank test

  5 years

Study Arms (1)

Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma

EXPERIMENTAL

Drug: Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma

Interventions

Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma DRUG

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

Acalabrutinib-rituximab in patients with untreated mantle cell lymphoma

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Nordic Lymphoma Group: lead
• AstraZeneca: collaborator

Study Sites (20)

Department of Hematology X, Odense University Hospital

Odense, Denmark

Location

Department of Hematology, Zeeland University Hospital Roskilde

Roskilde, Denmark

Location

Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center

Helsinki, Finland

Location

Oulu University Hospital

Oulu, Finland

Location

Department of Oncology, Haukeland University Hospital

Bergen, Norway

Location

Avd. for Kreftbehandling, Oslo Universitetssykehus

Oslo, Norway

Location

Avdeling for Blod- og Kreftsykdommer, Stavanger Universitetssykehus

Stavanger, Norway

Location

Kreftklinikken, St Olavs Hospital

Trondheim, Norway

Location

Division of Hematology-Oncology Samsung Medical Center Seoul

Seoul, South Korea

Location

Hematological Department, Falu Hospital, Falun

Falun, Sweden

Location

Department of Hematology and Coagulation, Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Department of Medicine, Halmstad Country Hospital

Halmstad, Sweden

Location

Department of Internal Medicine, Kalmar County Hospital

Kalmar, Sweden

Location

Hematologiska Kliniken, Universitetssjukhuset

Linköping, Sweden

Location

Department of Medicine, Sunderbyn Hospital

Luleå, Sweden

Location

Mats Jerkeman

Lund, Sweden

Location

Center of Hematology, Karolinska University Hospital

Stockholm, Sweden

Location

Uddevalla Hospital

Uddevalla, Sweden

Location

Cancercentrum, Norrlands Universitetsjukhus

Umeå, Sweden

Location

Department of Oncology, Uppsala Academic Hospital

Uppsala, Sweden

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Mats Jerkeman

  Department of Oncology, Skåne University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2021
• First Posted: January 28, 2022
• Study Start: December 15, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 12, 2024

Record last verified: 2024-02

Locations

FI (2); SE (11); KR (1); DK (2); NO (4)