ClinicalTrials.gov record NCT04883437
Acalabrutinib and Obinutuzumab for the Treatment of Previously Untreated Follicular Lymphoma or Other Indolent Non-Hodgkin Lymphomas
An Open-Label Phase 2 Trial of Acalabrutinib Plus Obinutuzumab in Patients With Untreated, Low Tumor Burden Follicular Lymphoma and Other Indolent Non-Hodgkin Lymphomas
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This is an open-label Phase 2 drug trial testing acalabrutinib (oral) combined with obinutuzumab (IV) as initial treatment for certain previously untreated, generally low‑tumor‑burden follicular and other indolent B‑cell lymphomas. Treatment is given in 28‑day cycles for up to 12 cycles; patients in complete response after induction are randomized to stop or continue acalabrutinib. The study measures response rates, side effects, duration of response, survival outcomes, and quality of life.
What it is studying. The study is testing whether the combination of acalabrutinib and obinutuzumab is effective and tolerable as initial (first‑line) treatment for people with previously untreated, low tumor burden follicular lymphoma and several other indolent B‑cell lymphomas. It measures tumor response (including complete response rate), safety (grade 3+ adverse events), duration of response, progression‑free and overall survival, and patient‑reported quality of life. The study also explores what happens if patients in complete response stop acalabrutinib after induction.
What the researchers hope to learn. Determine complete response and overall response rates to acalabrutinib plus obinutuzumab. Assess safety and frequency of grade 3 or higher adverse events. Measure duration of response, progression‑free survival, overall survival, and effects on quality of life. Explore outcomes after stopping acalabrutinib in patients who achieve complete response.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
This phase II trial studies the effect of acalabrutinib and obinutuzumab in treating patients with follicular lymphoma or other indolent non-Hodgkin lymphoma for which the patient has not received treatment in the past (previously untreated). Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib and obinutuzumab may kill more cancer cells.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Acalabrutinib
- Biological
- Obinutuzumab
- Other
- Quality-of-Life Assessment
- Questionnaire Administration
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Men and women >= 18 years of age
- Patients will need to have one of the following clinical scenarios:
- Previously untreated follicular lymphoma grade 1-3a with low tumor burden by Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
- Previously untreated follicular lymphoma grade 1-3a with high tumor burden by GELF criteria but who are unable or unwilling to receive standard front-line treatment approaches
- Previously untreated marginal zone lymphoma, lymphoplasmacytic lymphoma, or any other indolent B-cell lymphoproliferative disorder with low tumor burden by GELF criteria or who are unable/unwilling to receive more intensive front-line treatment
- Previously untreated mantle cell lymphoma who would otherwise be appropriate candidates for watchful waiting OR who have symptomatic disease but are not candidates for or decline standard induction approaches
- Patients with previously untreated low tumor burden FL (criterion above) must have measurable and/or assessable disease defined as at least one involved lymph node or extranodal disease site that measures >= 1.5cm in greatest diameter
- Patients who meet inclusion criteria above are eligible as long as they meet one of the following criteria for measurable/assessable disease:
- At least one involved lymph node or extranodal disease site measuring > 1.5cm in greatest diameter
- Pathologically-confirmed bone marrow or peripheral blood involvement that can be reassessed for response
- Pathologically confirmed splenic or extranodal involvement with at least one known site of disease remaining after diagnostic biopsy that can be reassessed (i.e., patients with splenic marginal zone lymphoma who complete splenectomy and have no other detectable disease would not be eligible)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Woman of childbearing potential (WOCBP) and men enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry for the duration of study participation, and for at least 2 days after the last dose of acalabrutinib or 18 months after the last dose of obinutuzumab, whichever is longer. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Women of childbearing potential must have a negative serum or urine pregnancy test prior to starting therapy
- Willing and able to participate in all required evaluations and procedures in this study protocol
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
Exclusion criteria
- The presence or history of histologically transformed or co-existing high-grade or aggressive non-Hodgkin lymphoma
- Confirmed active or prior central nervous system disease
- Prior receipt of lymphoma-directed therapy or prior antibody-based therapy (except for anti-microbial therapy for infection-associated marginal zone lymphoma such as hepatitis C or H pylori)
- A short course of steroids is permitted for patients aside from those in the low tumor burden FL cohort. This course may be no more than 14 days and steroids must be discontinued (or tapered to =< 10mg prednisone or equivalent) no later than 3 days after initiation of study treatment. Patients in the low tumor burden FL cohort may not receive corticosteroids as an anti-lymphoma therapy at any time before starting treatment
- Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for >= 2 years or which will not limit survival to < 5 years
- Clinically significant cardiovascular disease such as symptomatic ventricular 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. Note: Subjects with controlled, asymptomatic atrial fibrillation can enroll on study if deemed appropriate by the investigator
- Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
- Known history of human immunodeficiency (HIV) or any active significant infection (e.g., bacterial, viral, or fungal) within 14 days of cycle 1. Patients with uncomplicated viral or bacterial infections that are being managed with oral antibiotics and/or supportive care alone are eligible
- Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components
- Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
- Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
- Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening
- Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
- Requires treatment with proton pump inhibitors (e.g, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Note: Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study
- History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug. Patients with a transient ischemic attack which has resolved and for which there are no ongoing symptoms are eligible
- Major surgical procedure within 28 days of first dose of study drug (not including a diagnostic procedure to make the lymphoma diagnosis). Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
- Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative polymerase chain reaction (PCR) and must be willing to undergo deoxyribonucleic acid (DNA) PCR testing during the study to be eligible. Those who are HBsAg positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result to be eligible and have completed appropriate anti-viral treatment. Those who are hepatitis C PCR positive will be excluded. Anti-viral therapy for patients with hepatitis-C associated marginal zone lymphoma will not be considered a prior anti-lymphoma treatment
- Absolute neutrophil count (ANC) < 1,000/mcL
- Platelet count < 50,000/mcL (Unless felt to be related to underlying disease)
- Total bilirubin >= 1.5 x the upper limit of normal (ULN). Isolated bilirubin > 1.5 x ULN is permitted if the direct proportion is < 35%
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 x ULN
- Creatinine clearance =< 40 mL/min/1.73m\^2
- Breastfeeding or pregnant
- Concurrent participation in another therapeutic clinical trial
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
PRIMARY OBJECTIVE: I. To determine if treatment acalabrutinib and obinutuzumab is effective in patients with untreated, low tumor burden follicular lymphoma and other indolent non-Hodgkin lymphomas (NHLs). SECONDARY OBJECTIVES: I. Determine the complete response (CR) rate for single agent acalabrutinib at the end of a single-agent run-in for patients with untreated low tumor burden follicular lymphoma (FL). II. Determine tolerability of acalabrutinib and obinutuzumab via assessment of patient-reported outcomes and conventional assessments. III. Assess duration of response and long-term outcomes including progression-free survival. IV. Assess the impact of early treatment with this regimen on health-related quality of life. TERTIARY/EXPLORATORY OBJECTIVES: I. Evaluate the impact of treatment discontinuation in patients who have achieved a complete response at the end of the induction phase. II. To assess the safety and efficacy of acalabrutinib and obinutuzumab in other subtypes of indolent NHL. OUTLINE: INDUCTION PHASE: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of cycle 3, then on day 1 of cycles 4-8. Treatments repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. FOLLOW-UP PHASE: After cycle 12, patients who are in CR are randomized to either discontinue acalabrutinib or to continue acalabrutinib monotherapy in the absence of disease progression or unacceptable toxicity. Patients with partial response (PR) or stable disease (SD) after cycle 12 continue acalabrutinib monotherapy in the absence of disease progression or unacceptable toxicity. Patients with disease progression after cycle 12 discontinue study treatment. Patients with disease progression at any time prior to the conclusion of cycle 12 may continue study therapy if they are felt to be benefiting by the treating physician, but not past cycle 12. After completion of study treatment, patients are followed up at 30 days, every 12 weeks for 1 year, then every 6 months until disease progression or next anti-lymphoma treatment.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants take oral acalabrutinib twice daily in 28‑day cycles and receive intravenous obinutuzumab infusions on scheduled days during the induction phase (cycles 3–8). Treatment repeats every 28 days for up to 12 cycles unless disease progression or unacceptable toxicity occurs. You will complete quality‑of‑life questionnaires and have regular safety checks (clinic visits, blood tests, and imaging as needed); after cycle 12 people in complete response are randomized to stop or continue acalabrutinib, while those with partial response or stable disease continue acalabrutinib monotherapy. Follow‑up visits occur at 30 days after treatment, then every 12 weeks for one year, then every 6 months until disease progression or next lymphoma treatment.
How the study is structured. Interventional, open‑label Phase 2 study. All participants start induction with oral acalabrutinib twice daily; IV obinutuzumab infusions begin in cycle 3. Treatment is given across 28‑day cycles for up to 12 cycles. After cycle 12, people in complete response are randomized to either stop acalabrutinib or continue acalabrutinib alone; those with partial response or stable disease continue acalabrutinib monotherapy. The study includes regular assessments during treatment and follow‑up visits after treatment completion to track response, side effects, and quality of life.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- Sep 3, 2021
- Primary completion
- Sep 23, 2026 (estimated)
- Study completion
- Jan 15, 2027 (estimated)
- Target enrollment
- 49 participants (estimated)
- Last updated on registry
- Feb 9, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Emory University
- Principal investigator
- Jonathon Cohen, Principal Investigator
Emory University - Collaborators
- AstraZeneca
- National Cancer Institute (NCI)
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Jonathon Cohen, MD, MS 📞 404-778-2419 ✉ jonathon.cohen@emory.edu
Participating sites (1)
- Emory University Hospital/Winship Cancer InstituteRecruiting
Atlanta, Georgia, 30322 · United States
- David Reagan · 404-251-1275 · dreagan@emory.edu
- Jonathon Cohen, MD,MS
Terms used on this page · explanations by MedicalUpdates.ai
- previously untreated
- Has not previously received the treatment, or the type of treatment, that the study is about.
- inclusion criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- ECOG
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- cohort
- A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
- prednisone
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- before screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- Absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- PRIMARY OBJECTIVE
- The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
- complete response
- No sign of the condition can be found with the tests used in the study. It does not always mean the condition is gone permanently, and the definition depends on the condition and the study.
- run-in
- A period at the start of a study, before the study treatment begins, used for example to confirm that participants meet the criteria or to record their usual symptoms.
- progression-free survival
- The length of time during and after treatment that a person lives without the condition getting worse, as defined by the study.
- FOLLOW-UP
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- randomized
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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