Acalabrutinib and Obinutuzumab for the Treatment of Previously Untreated Follicular Lymphoma or Other Indolent Non-Hodgkin Lymphomas

NCT04883437 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00002247NCI-2021-00894WINSHIP5186-20P30CA138292
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Indolent Non-Hodgkin Lymphoma; Lymphoplasmacytic Lymphoma; Lymphoproliferative Disorder; Mantle Cell Lymphoma; Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (2)

• Complete response (CR) rate

  Complete response rate will be calculated, and a 95% confidence interval will be estimated using the Clopper-Pearson method.

  Up to start of cycle 6 (each cycle = 28 days)

• Incidence of grade 3+ adverse events

  Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 30 days post treatment

Secondary Outcomes (8)

• Overall response rate

  Up to 3 years

• CR rate for acalabrutinib monotherapy at end of single-agent run-in

  Up to 3 years

• 2-year progression free survival (PFS)

  From first dose to documented disease progression, or death from any cause, whichever occurs first, assessed at 2 years

• Overall survival (OS)

  From first dose to death from any cause, assessed up to 3 years

• Duration of response (DOR)

  From the first tumor assessment supports the response to the time of confirmed disease progression or death due to any cause, whichever occurs first, assessed up to 3 years

Study Arms (1)

Treatment (acalabrutinib, obinutuzumab)

EXPERIMENTAL

INDUCTION PHASE: Patients receive acalabrutinib PO BID on days 1-28. Patients also receive obinutuzumab 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 PR or 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.

Drug: Acalabrutinib; Biological: Obinutuzumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Acalabrutinib DRUG

Given PO

Also known as: ACP-196, Bruton Tyrosine Kinase Inhibitor ACP-196, Calquence

Treatment (acalabrutinib, obinutuzumab)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Treatment (acalabrutinib, obinutuzumab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (acalabrutinib, obinutuzumab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (acalabrutinib, obinutuzumab)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• AstraZeneca: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoproliferative Disorders; Lymphoma, Mantle-Cell

Interventions

acalabrutinib; obinutuzumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Jonathon B Cohen, MD, MS

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonathon Cohen, MD, MS

CONTACT

404-778-2419; jonathon.cohen@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: May 12, 2021
• Study Start: September 3, 2021
• Primary Completion (Estimated): September 23, 2026
• Study Completion (Estimated): January 15, 2027
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (1)