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Ann Arbor Stage III Grade 1 Follicular LymphomaPhase 2NCT04404088

Acalabrutinib, Lenalidomide, and Rituximab for the Treatment of CD20 Positive Stage III-IV, Grade 1-3a Follicular Lymphoma

A Phase 2 study testing Acalabrutinib, Lenalidomide and Rituximab in people with Ann Arbor Stage III Grade 1 Follicular Lymphoma and Ann Arbor Stage III Grade 2 Follicular Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase II trial studies how well acalabrutinib, lenalidomide, and rituximab work in treating patients with CD20 positive stage III-IV, grade 1-3a follicular lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Acalabrutinib, Lenalidomide and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteUnited States
Study dates
16 Jul 2020to 1 Mar 2028
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed CD20 positive (+) follicular lymphoma, grade 1, 2, or 3a
  • Have had no prior systemic treatment for lymphoma
  • Bi-dimensionally measurable disease, with at least one mass lesion >= 2 cm in longest diameter by computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI)
  • Meeting Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria for initiation of treatment
  • Stage III or IV disease
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
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  • Absolute neutrophil count (ANC) >= 1,000/mm^3, independent of growth factor support (within 28 days prior to signing informed consent)
  • Platelet counts >= 100,000/mm^3 or >= 50,000/mm^3 if bone marrow involvement with lymphoma, independent of transfusion support in either situation (within 28 days prior to signing informed consent)
  • Hemoglobin > 8 g/dL, independent of transfusion support (within 28 days prior to signing informed consent)
  • Serum aspartate transaminase (AST) or alanine transaminase (ALT) < 2 x upper limit of normal (ULN) (within 28 days prior to signing informed consent)
  • Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula (within 28 days prior to signing informed consent)
  • Bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL (within 28 days prior to signing informed consent)
  • Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN (within 28 days prior to signing informed consent)
  • Must be able to adhere to the study visit schedule and other protocol requirements
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study (females of childbearing potential: must either completely abstain from heterosexual sexual conduct or must use 2 methods of reliable contraception, 1 highly effective [intrauterine device, birth control pills, hormonal patches, injections, vaginal rings, or implants] and at least 1 additional method [condom, diaphragm, cervical cap] of birth control). Reliable contraceptive methods must be started at least 4 weeks before lenalidomide, and continued for at least 4 weeks after last dose of lenalidomide. Males who are sexually active must be practicing complete abstinence or agree to a condom during sexual contact with a pregnant female or female of child bearing potential. Men must agree to not donate sperm during and after the study. For females, these restrictions apply at least 4 weeks before study treatment, during the period of therapy and for 1 month after the last dose of study drug. For males, these restrictions apply during the period of therapy and for 3 months after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategies (REMS) program
  • Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
  • All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the REMS program

Who cannot join

  • Known active central nervous system lymphoma or leptomeningeal disease, except subjects with a history of central nervous system lymphoma treated and in remission > 6 months
  • Evidence of diffuse large B-cell transformation
  • Grade 3b FL
  • Any prior history of other malignancy besides FL or marginal zone lymphoma, unless the patient has been free of disease for >= 5 years and felt to be at low risk for recurrence by the treating physician, except:
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated cervical carcinoma in situ without evidence of disease
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  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib or lenalidomide capsules, or put the study outcomes at undue risk
  • Known history of human immunodeficiency virus (HIV), or active hepatitis C Virus, or active hepatitis B Virus infection, or any uncontrolled active significant infection, including suspected or confirmed John Cunningham (JC) virus infection
  • Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated. Hepatitis B or C serologic status: subjects 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). Those who are hepatitis B surface antigen (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. Those who are hepatitis C PCR positive will be excluded. Subjects with a history of Hepatitis C who received antiviral treatment are eligible as long as PCR is negative
  • Concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of > 10 mg/day of prednisone) within 28 days of the first dose of study drug
  • Known anaphylaxis or immunoglobulin (Ig) E-mediated hypersensitivity to murine proteins or to any component of acalabrutinib, lenalidomide and/or rituximab
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon). If patients have been on warfarin or equivalent vitamin K antagonists in the past, they will not be eligible if administered within 30 days of the first dose of study drug
  • Requires chronic treatment with strong CYP3A inhibitors, for a list of strong CYP3A inhibitors. If patients have been on a strong CYP3A inhibitor in the past, they will not be eligible if the CYP3A inhibitor was administered within 7 days of the first dose of study drug
  • Requires chronic treatment with strong CYP3A inducers, for a list of strong CYP3A inducers. If patients have been on a strong CYP3A inducer in the past, they will not be eligible if the CYP3A inducer was administered within 7 days of the first dose of study drug
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association functional classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study
  • Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block
  • Active bleeding or known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia
  • History of stroke or intracranial hemorrhage within 6 months prior to study entry
  • Vaccinated with live, attenuated vaccines within 4 weeks of study entry
  • Lactating or pregnant subjects
  • Administration of any investigational agent within 28 days of first dose of study drug
  • Patients who have undergone major surgery within 28 days or minor surgery within 3 days of first dose of study drug
  • Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisone (over these 4 weeks)
  • Life expectancy < 6 months
  • Neuropathy > grade 1
  • Prior exposure to lenalidomide or to a BCR inhibitor, independently from indication
  • Patient who require treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole), and are unable to switch to H2-receptor antagonists
  • Patients who have difficulty with or are unable to swallow oral medication, or have disease significantly affecting gastrointestinal function that would limit absorption of oral medication
  • Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)
  • Known history of deep vein thrombosis or pulmonary embolism
  • Known history of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) or drug rash with eosinophilia and systemic symptoms (DRESS)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Paolo Strati contact

713-745-1776

pstrati@mdanderson.org

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Paolo Strati, 713-792-0084, pstrati@mdanderson.org

    Paolo Strati

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Study of Acalabrutinib, Lenalidomide, and Rituximab (aR2) in Patients With Previously Untreated Follicular Lymphoma

This phase II trial studies how well acalabrutinib, lenalidomide, and rituximab work in treating patients with CD20 positive stage III-IV, grade 1-3a follicular lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib, lenalidomide, and rituximab may help to control the disease.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the efficacy of acalabrutinib combined with rituximab and lenalidomide in patients with previously untreated follicular lymphoma (FL) (determined by complete remission [CR] rate by the end of treatment).

SECONDARY OBJECTIVES:

  1. To evaluate the efficacy of acalabrutinib combined with rituximab and lenalidomide in subjects with FL as assessed by objective response rate (ORR) at the end of treatment, duration of response (DOR), progression rate within 24 months from treatment initiation (progression-free survival [PFS] 24), PFS and overall survival (OS).

II. To evaluate the safety and tolerability of acalabrutinib combined with rituximab and lenalidomide in previously untreated subjects with FL.

EXPLORATORY OBJECTIVE:

  1. To determine the pharmacodynamic effects and investigate biomarkers of response and resistance of the 3-drug combination.

OUTLINE:

Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Beginning cycle 2, patients receive lenalidomide PO once daily (QD) on days 1-21 and rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycle 2 and day 1 of subsequent cycles. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.

Being tested
Acalabrutinib, Lenalidomide, Rituximab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AcalabrutinibDrug

    Also called ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence

    Given PO

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT04404088
Study groupRoleWhat they receive
Treatment (acalabrutinib, lenalidomide, rituximab)ExperimentalPatients receive acalabrutinib PO BID on days 1-28. Beginning cycle 2, patients receive lenalidomide PO QD on days 1-21 and rituximab IV on days 1, 8, 15, and 22 of cycle 2 and day 1 of subsequent cycles. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Acalabrutinib; Drug: Lenalidomide; Biological: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete remission rate

    Will be based on Cheson, Lugano classification 2014. The number and percentage of subjects with a complete remission at the end of treatment will be tabulated.

    Measured: (Up to end of treatment; 1 year)

Secondary outcomes (7)

  1. Overall response rate (complete response + partial response)

    Will be based on Cheson, Lugano classification 2014. The number and percentage of subjects with an overall response rate will be tabulated. The best overall response rate will be recorded.

    Measured: (At the end of treatment ; 1 year )

  2. Duration of response

    Will be based on Cheson, Lugano classification 2014. Cox proportional hazards models will be used to assess the effects of patient prognostic factors on duration of response. Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval.

    Measured: From the time by which measurement criteria for complete response or partial response, whichever is recorded first, is met until death or the first date by which progressive disease is documented, assessed up to 3 years

  3. Progression-free survival within 24 months from treatment initiation

    Will be estimated by the Kaplan-Meier method. Corresponding 95% confidence intervals will be summarized. Cox proportional hazards models will be used to assess the effects of patient prognostic factors on progression-free survival.

    Measured: From the treatment start date (cycle 1, day 1) until the firstdate of objectively documented progressive disease or date of death from any cause, assessed up to 24 months

  4. Progression-free survival

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Cox proportional hazards models will be used to assess the effects of patient prognostic factors on progression-free survival.

    Measured: From the date of cycle 1, day 1 to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death, assessed up to 3 years

  5. Overall survival

    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Cox proportional hazards models will be used to assess the effects of patient prognostic factors on overall survival.

    Measured: From the date of cycle 1, day 1 to the date of death regardless of cause, assessed up to 3 years

  6. Frequency, severity, and relatedness of treatment-emergent adverse events (AEs)

    Adverse experiences will be graded and recorded throughout the study and during the follow-up period according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5. Safety summaries will include tabulations in the form of tables and listings. The frequency (number and percentage) of treatment-emergent AEs will be reported. Additional AE summaries will include AE frequency by AE severity and by relationship to study drug. Clinically significant abnormal laboratory values will be summarized.

    Measured: Up to 3 years

  7. Frequency of treatment-emergent AEs requiring study drug discontinuation or dose reduction

    Adverse experiences will be graded and recorded throughout the study and during the follow-up period according to NCI CTCAE version 5. Safety summaries will include tabulations in the form of tables and listings. The frequency (number and percentage) of treatment-emergent AEs will be reported. Additional AE summaries will include AE frequency by AE severity and by relationship to study drug. Clinically significant abnormal laboratory values will be summarized.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2020
  2. Study start16 Jul 2020
  3. Primary completion1 Mar 2028 (estimated)
  4. Study completion1 Mar 2028 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04404088
Sponsor's protocol ID
2020-0034
Other IDs
NCI-2020-01922, 2020-0034
Status last verified
Oct 2026
First submitted
12 May 2020
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Acalabrutinib, Lenalidomide and Rituximab in people with Ann Arbor Stage III Grade 1 Follicular Lymphoma and Ann Arbor Stage III Grade 2 Follicular Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

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 19 inclusion and 31 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: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Contact Paolo Strati (713-745-1776, pstrati@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete remission rate (time frame: (Up to end of treatment; 1 year)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04404088.

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 2 Nov 2026.

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