Study of Acalabrutinib Alone or in Combination Therapy in Subjects With B-cell Non-Hodgkin Lymphoma

NCT02180711 | Active Not Recruiting Phase 1 Results

• 3 other identifiers: ACE-LY-0032023-509350-63-002019-000111-84
• Study Type: interventional
• Target: 113
• Locations: 3 countries
• Sites: 32

Brief Summary

Part 1: To characterize the safety profile of acalabrutinib alone or in combination with rituximab in subjects with R/R FL. Part 2: To characterize the activity of acalabrutinib alone or in combination with rituximab in subjects with R/R MZL, as measured by ORR. Part 3: To characterize the safety of acalabrutinib in combination with rituximab and lenalidomide in subjects with R/R FL

Conditions

Non Hodgkin Lymphoma

Keywords

Bruton tyrosine kinase inhibitor; Btk; Follicular Lymphoma; FL; acalabrutinib; ACP-196; MZL; Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (3)

• Part 1: Incidence of Treatment-emergent Adverse Events.

  Treatment-emergent adverse events were used to characterize the safety profile of acalabrutinib alone or in combination with rituximab in participants with relapsed/refractory follicular lymphoma (R/R FL).

  From the first dose of study drug until study discontinuation, 30 days after the last dose of study drug or one day before the first subsequent anticancer therapy, whichever was earlier, up to 80.7 months (the maximum participant's time on this study).

• Part 2: Investigator Assessed Objective Response Rate (ORR) According to the Lugano Classification for Non-Hodgkin Lymphoma (NHL).

  The objective response rate (ORR) is used to characterize the activity of acalabrutinib alone or in combination with rituximab in participants with relapsed/refractory marginal zone lymphoma (R/R MZL).

  Based on all response assessments since the first dose of study drug until study discontinuation or the initiation of subsequent anticancer therapy, whichever was earlier, up to 65.1 months (the maximum participant's time on this study).

• Part 3: Incidence of Treatment-emergent Adverse Events.

  Treatment-emergent adverse events were used to characterize the safety of acalabrutinib in combination with rituximab and lenalidomide in participants with relapsed/refractory follicular lymphoma (R/R FL).

  From the first dose of study drug until study discontinuation, 30 days after the last dose of study drug or one day before the first subsequent anticancer therapy, whichever was earlier, up to 54.3 months (the maximum participant's time on this study).

Study Arms (5)

Part 1: acalabrutinib Regimen 1

EXPERIMENTAL

acalabrutinib Regimen 1 for relapsed, refractory Follicular Lymphoma subjects

Drug: acalabrutinib

Part 1: acalabrutinib Regimen 2

EXPERIMENTAL

acalabrutinib Regimen 2 + rituximab for relapsed, refractory, or treatment naive Follicular Lymphoma subjects

Drug: acalabrutinib; Drug: rituximab (IV)

Part 2: acalabrutinib Regimen 1

EXPERIMENTAL

acalabrutinib Regimen 1 for relapsed, refractory Marginal Zone Lymphoma subjects

Drug: acalabrutinib

Part 2: acalabrutinib Regimen 2

EXPERIMENTAL

acalabrutinib Regimen 2 + rituximab for relapsed, refractory Marginal Zone Lymphoma subjects

Drug: acalabrutinib; Drug: rituximab (IV)

Part 3: acalabrutinib Regimen 1

EXPERIMENTAL

acalabrutinib Regimen + lenalidomide + rituximab for relapsed, refractory Follicular Lymphoma subjects

Drug: acalabrutinib; Drug: rituximab (IV); Drug: Lenalidomide

Interventions

acalabrutinib DRUG

Also known as: ACP-196

Part 1: acalabrutinib Regimen 1; Part 1: acalabrutinib Regimen 2; Part 2: acalabrutinib Regimen 1; Part 2: acalabrutinib Regimen 2; Part 3: acalabrutinib Regimen 1

rituximab (IV) DRUG

Part 1: acalabrutinib Regimen 2; Part 2: acalabrutinib Regimen 2; Part 3: acalabrutinib Regimen 1

Lenalidomide DRUG

Part 3: acalabrutinib Regimen 1

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.
• Part 1: A confirmed diagnosis of FL Grade 1, 2, or 3a, which has relapsed after, or been refractory to ≥ 1 prior therapy for FL, or subjects who have not previously received systemic anticancer therapy for FL., and which requires treatment.
• Part 2: For subject with relapsed or refractory MZL:
• Histologically confirmed MZL including splenic, nodal, and extranodal sub-types
• Subjects with gastric mucosa-associated lymphoid tissue (MALT) lymphoma must be Helicobacter pylori (HP)-negative
• Part 3: For subjects with FL: Pathologically confirmed diagnosis of FL Grade 1, 2, or 3a, which has relapsed after, or been refractory to ≥ 1 prior therapy for FL and which requires treatment per National Cancer Institute or ESMO clinical practice guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.

You may not qualify if:

• A 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 put the study outcomes at undue risk
• Significant cardiovascular disease such as uncontrolled or symptomatic 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, or Qtc \>480 msec
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Breast feeding or pregnant

Sponsors & Collaborators

• Acerta Pharma BV: lead
• AstraZeneca: collaborator

Study Sites (32)

Research Site

Tucson, Arizona, 85719, United States

Location

Research Site

Downey, California, 90241, United States

Location

Research Site

Duarte, California, 91010, United States

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Fountain Valley, California, 92708, United States

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Santa Monica, California, 90404, United States

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Coral Gables FL, Florida, 33146, United States

Location

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Chicago, Illinois, 60611, United States

Location

Research Site

Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60637, United States

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Louisville, Kentucky, 40207, United States

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New Orleans, Louisiana, 70112, United States

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Ann Arbor, Michigan, 48109, United States

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Morristown, New Jersey, 07960, United States

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Hawthorne, New York, 10532, United States

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Lake Success, New York, 11042, United States

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New York, New York, 10021, United States

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Syracuse, New York, 13210, United States

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Columbus, Ohio, 43210, United States

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Greenville, South Carolina, 29615, United States

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Dallas, Texas, 75235, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78217, United States

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Temple, Texas, 76508, United States

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Salt Lake City, Utah, 84112, United States

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Spokane, Washington, 99208, United States

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Waukesha, Wisconsin, 53188, United States

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Edmonton, Alberta, t6G1Z2, Canada

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London, Ontario, N6A 5W9, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Bologna, 40138, Italy

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Milan, 20132, Italy

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Research Site

Palermo, 90146, Italy

Location

Related Links

• Redacted CSP
• Redacted SAP
• Redacted CSR synopsis

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

acalabrutinib; Rituximab; Lenalidomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2014
• First Posted: July 3, 2014
• Study Start: December 29, 2014
• Primary Completion: August 25, 2023
• Study Completion (Estimated): December 29, 2028
• Last Updated: October 15, 2025
• Results First Posted: October 15, 2025

Record last verified: 2025-09

Locations

US (26); CA (3); IT (3)