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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 (ARCHED/GLA 2022-1)
EU CTIS ID: 2022-501187-18-00
What this study is testing
To evaluate if the addition of acalabrutinib to R-miniCHOP prolongs progression-free survival (PFS), compared to R-miniCHOP alone in patients >80 years or >60 years and ineligible for full-dose R-CHOP with previously untreated DLBCL, based on investigator-assessed response.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Ability to understand the purpose and risks of the study and capable of giving signed informed consent which includes: a. Compliance with the requirements and restrictions listed in the informed consent form (ICF). b. Authorization to use protected health information/data [in accordance with the General Data Protection Regulation (GDPR)].
- Meet the following laboratory parameters: a. Absolut neutrophil count (ANC) ≥ 1500 cells/µl or platelet count ≥ 100.000/µl unless directly attributable to lymphoma. b. Serum AST and ALT ≤3 x upper limit of normal (ULN) unless directly attributable to lymphoma. c. Total bilirubin ≤1.5 x ULN, unless directly attributable to Gilbert’s syndrome or lymphoma. d. Estimated creatinine clearance of ≥30 mL/min, calculated by Cockcroft-Gault (using actual body weight) (if male, [140-Age] x Mass [kg] / [72 x serum creatinine mg/dL]; multiply by 0.85 if female), or serum creatinine ≤2.5 x ULN.
- Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses
- Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
- 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 after standardized geriatric assessment
- Male patients who are sexually active with women of childbearing potential (definitions see section 17.8 of the protocol) 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 of the protocol) as well as to the restrictions mentioned in section 9.13 of the protocol
You likely can't join if
- 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)].
- Concurrent participation in another therapeutic clinical trial.
- Any active significant infection (e.g., bacterial, viral or fungal) as assessed by the investigator.
- Severe pulmonary dysfunction (CTCAE grade 3 or 4) unless associated with lymphoma.
- 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.
- Persistent neuropathy CTCAE grade 3 or 4
See the full eligibility criteria
Who can join
- Ability to understand the purpose and risks of the study and capable of giving signed informed consent which includes: a. Compliance with the requirements and restrictions listed in the informed consent form (ICF). b. Authorization to use protected health information/data [in accordance with the General Data Protection Regulation (GDPR)].
- Meet the following laboratory parameters: a. Absolut neutrophil count (ANC) ≥ 1500 cells/µl or platelet count ≥ 100.000/µl unless directly attributable to lymphoma. b. Serum AST and ALT ≤3 x upper limit of normal (ULN) unless directly attributable to lymphoma. c. Total bilirubin ≤1.5 x ULN, unless directly attributable to Gilbert’s syndrome or lymphoma. d. Estimated creatinine clearance of ≥30 mL/min, calculated by Cockcroft-Gault (using actual body weight) (if male, [140-Age] x Mass [kg] / [72 x serum creatinine mg/dL]; multiply by 0.85 if female), or serum creatinine ≤2.5 x ULN.
- Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses
- Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
- 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 after standardized geriatric assessment
- Male patients who are sexually active with women of childbearing potential (definitions see section 17.8 of the protocol) 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 of the protocol) as well as to the restrictions mentioned in section 9.13 of the protocol
- Female patients of childbearing potential (definitions see 17.8 in the protocol) 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. of the protocol
- Histologically proven, previously untreated CD20+ diffuse large B-cell lymphoma (DLBCL) according to the 2017 WHO classification including: a. diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) b. primary cutaneous DLBCL leg type c. intravascular large B-cell lymphoma d. EBV+ DLBCL, NOS e. HHV8+DLBCL, NOS f. primary mediastinal (thymic) large B-cell lymphoma g. B-cell lymphoma, with intermediate features between DLBCL and classical Hodgkin lymphoma h. follicular lymphoma grade 3B i. high-grade B-cell lymphoma, NOS j. high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements k. T-cell/histiocyte-rich large B-cell lymphoma l. DLBCL associated with chronic inflammation m. ALK+ large B-cell lymphoma n. 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
- Disease Stage I with bulk ≥7.5cm, II, III or IV according to Ann Arbor Classification
- 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
What rules you out
- 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)].
- Concurrent participation in another therapeutic clinical trial.
- Any active significant infection (e.g., bacterial, viral or fungal) as assessed by the investigator.
- Severe pulmonary dysfunction (CTCAE grade 3 or 4) unless associated with lymphoma.
- 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.
- Persistent neuropathy CTCAE grade 3 or 4
- 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.
- History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following: a. 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. b. 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.
- Received a live virus vaccination within 28 days of randomization.
- Known history of infection with HIV.
- History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
- Diagnosis of primary central nervous system lymphoma or secondary central nervous system or meningeal involvement by lymphoma
- Serologic status reflecting active hepatitis B or C infection. a. 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. b. 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.
- History of stroke or intracranial hemorrhage within 6 months before randomization
- History of clinically relevant bleeding diathesis (e.g., hemophilia, von Willebrand disease).
- 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.
- Breastfeeding or pregnant women
- 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.
- Diagnosis of Richter’s Transformation/transformed CLL
- 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.
- 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.
- 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 of the protocol
- Prior exposure to a BTK inhibitor.
- Prior anthracycline use >300 mg/m2 of doxorubicin equivalent.
- Already initiated lymphoma therapy except for steroid (max. total dose of 1500mg of prednisolone equivalent), vincristine (max. 1 mg once) and/or rituximab (max. total dose of 375mg/m2) prephase.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.