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Combining Acalabrutinib with R-miniCHOP for older adults with untreated diffuse large B-cell lymphoma

A Randomized, Open-label, Phase 3 Study of Acalabrutinib in Combination With Rituximab and Reduced Dose CHOP (R-miniCHOP) in OldEr Adults With Untreated Diffuse Large B-Cell Lymphoma

Phase 3 Interventional Universität des Saarlandes · NCT05820841

This study tests if adding Acalabrutinib to the usual treatment for older adults with untreated diffuse large B-cell lymphoma can help them live longer without their cancer getting worse.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment330 (estimated)
Ages61 Years and up
SexAll
SponsorUniversität des Saarlandes Academic / other
Drugs / interventionsrituximab, acalabrutinib, chemotherapy, radiation
Locations17 sites (Homburg, Saarland and 16 other locations)
Trial IDNCT05820841 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of adding Acalabrutinib to the standard treatment regimen of R-miniCHOP in older adults diagnosed with untreated diffuse large B-cell lymphoma (DLBCL). Participants will be randomly assigned to receive either R-miniCHOP alone or the combination treatment. The primary objective is to determine if the addition of Acalabrutinib can prolong progression-free survival in this patient population. The study focuses on older adults, particularly those who may not tolerate full-dose chemotherapy.

Who should consider this trial

Good fit: Ideal candidates are older adults aged 60 and above who are ineligible for full-dose R-CHOP due to health conditions.

Not a fit: Patients who are younger than 60 or those who can tolerate full-dose R-CHOP may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could improve survival outcomes for older patients with DLBCL.

How similar studies have performed: Other studies have shown promising results with similar treatment combinations in older adults with aggressive lymphomas, suggesting potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

Informed consent

1. Ability to understand the purpose and risks of the study and capable of giving signed informed consent which includes:

   1. Compliance with the requirements and restrictions listed in the informed consent form (ICF).
   2. Authorization to use protected health information/data \[in accordance with the General Data Protection Regulation (GDPR)\].
2. Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses
3. Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.

   Age/Sex
4. Men and women \>80 years of age or \>60 up to 80 years of age and ineligible for full dose R-CHOP according to investigator assessment\*.

   We recommend classifying patients aged 61-80 as full-dose R-CHOP ineligible if they fulfill one of the following criteria: ADL \<5, IADL \<6, CIRS-G ≥1 score = 3, or \> 8 score = 2.
5. Male patients who are sexually active with women of childbearing potential (definitions see section 17.8) must agree to use highly effective forms of contraception with the addition of a barrier method (condom) during the study (see section 17.8.1) as well as to the restrictions mentioned in section 9.13.
6. Female patients of childbearing potential (definitions see 17.8) who are sexually active must agree to use highly effective forms of contraception while on the study as well as to the restrictions mentioned in section 9.13.

   Disease characteristics
7. Histologically proven, previously untreated CD20+ diffuse large B-cell lymphoma (DLBCL) according to the 2017 WHO classification including:

   1. diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
   2. primary cutaneous DLBCL leg type
   3. intravascular large B-cell lymphoma
   4. EBV+ DLBCL, NOS
   5. HHV8+DLBCL, NOS
   6. primary mediastinal (thymic) large B-cell lymphoma
   7. B-cell lymphoma, with intermediate features between DLBCL and classical Hodgkin lymphoma
   8. follicular lymphoma grade 3B
   9. high-grade B-cell lymphoma, NOS
   10. high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
   11. T-cell/histiocyte-rich large B-cell lymphoma
   12. DLBCL associated with chronic inflammation
   13. ALK+ large B-cell lymphoma
   14. large B-cell lymphoma with IRF4 rearrangement Please note: patients in whom indolent lymphoma is diagnosed concurrently with the one of the above listed diagnoses can also be included.
8. Disease Stage I with bulk ≥7.5cm, II, III or IV according to Ann Arbor Classification Type of patient and clinical characteristics
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. An ECOG Score of 3 is acceptable only if this is directly attributable to lymphoma.
10. Meet the following laboratory parameters:

    1. Absolute neutrophil count (ANC) ≥ 1500 cells/µl or platelet count ≥ 100.000/µl unless directly attributable to lymphoma.
    2. Serum AST and ALT ≤3 x upper limit of normal (ULN) unless directly attributable to lymphoma.
    3. Total bilirubin ≤1.5 x ULN, unless directly attributable to Gilbert's syndrome or lymphoma.
    4. Estimated creatinine clearance of ≥30 mL/min, calculated by Cockcroft-Gault (using actual body weight) (if male, \[140-Age\] x Mass \[kg\] / \[72 x creatinine mg/dL\]; multiply by 0.85 if female), or serum creatinine ≤2.5 x ULN.

Exclusion Criteria:

Medical conditions

1. Evidence of disease (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension and renal transplant) that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol \[e.g. a single score of 4 on one single category on the CIRS-G-Score (but not a cumulative score of 4)\].
2. Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of randomization or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or LVEF \< 40%. Patients with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
3. Severe pulmonary dysfunction (CTCAE grade 3 or 4) unless associated with lymphoma.
4. Severe psychiatric or neurologic disease that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol.
5. Persistent neuropathy CTCAE grade 3 or 4.
6. Refractory nausea and vomiting, inability to swallow acalabrutinib, or malabsorption syndrome; chronic severe gastrointestinal disease, gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment.
7. History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:

   1. Curatively treated localised basal cell carcinoma or localised squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ / low risk carcinoma of the prostate requiring only observation, as well as untreated low grade lymphoma except chronic lymphocytic leukemia.
   2. Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which patient is disease-free for ≥2 years (≥5 years for those treated with chemotherapy) without further treatment or which are not expected to limit survival to \< 2 years.
8. Received a live virus vaccination within 28 days of randomization.
9. Known history of infection with HIV.
10. Any active significant infection (e.g., bacterial, viral or fungal) as assessed by the investigator.
11. History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
12. Serologic status reflecting active hepatitis B or C infection.

    1. Patients who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before randomization and must be willing to undergo DNA PCR testing during the study. Those who are HBsAg-positive or hepatitis B PCR positive will be excluded.
    2. Patients who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis C PCR positive will be excluded.
13. History of stroke or intracranial hemorrhage within 6 months before randomization.
14. History of clinically relevant bleeding diathesis (e.g., hemophilia, von Willebrand disease).
15. Major surgical procedure within 30 days before randomization. Note: If a patient had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
16. Breastfeeding or pregnant women.
17. Current life-threatening illness, medical condition, organ system dysfunction, social, geographical or economic condition which, in the Investigator's opinion, could compromise the patient's safety or put the study at risk.
18. Diagnosis of primary central nervous system lymphoma or secondary central nervous system or meningeal involvement by lymphoma
19. Diagnosis of Richter's Transformation/transformed CLL Prior/Concomitant therapy
20. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists. Patients using therapeutic low molecule weight heparin, direct oral anticoagulants or low dose aspirin will be eligible. Switching from vitamin K antagonists to one of the allowed anticoagulants above prior to trial entry is permitted.
21. Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor or inducer. 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. See details in section 9.12.1.
22. Prior exposure to a BTK inhibitor.
23. Prior anthracycline use ≥300 mg/m2.
24. Already initiated lymphoma therapy except for steroid (max. total dose of 1000mg), vincristine (max. 1 mg once) or rituximab (max. 375mg/m2) prephase.
25. Concurrent participation in another therapeutic clinical trial.
26. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrolment into this study.
27. Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.

Where this trial is running

Homburg, Saarland and 16 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Large B-cell LymphomaDiffuse Large B Cell LymphomaDiffuse large B cell lymphomaOlder adultsGeriatricLarge B cell lymphomaAggressive B cell lymphomaAcalabrutinib
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.