Acalabrutinib and Duvelisib for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin Lymphoma

NCT04836832 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-20179NCI-2021-01355
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase Ib/II trial studies the side effects of acalabrutinib and duvelisib and how well they work in treating patients with indolent non-Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Acalabrutinib inhibits a signaling molecule called Bruton tyrosine kinase and blocks cancer cell proliferation, growth, and survival. Duvelisib is designed to block a protein called PI3 kinase in order to stop cancer growth and cause changes in the immune system that may allow the immune system to better act against cancer cells. Giving acalabrutinib and duvelisib together may work better to block cancer growth than therapy of either drug alone.

Conditions

Recurrent Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Follicular Lymphoma; Refractory Indolent Non-Hodgkin Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Splenic Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Adverse events and toxicities of the combination regimen will be summarized using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5 criteria; toxicities will be tabulated overall and also by dose level.

  Up to 30 days after completion of treatment

• Overall response rate (ORR) (assessed by computed tomography)

  Will be defined as the proportion of patients achieving a complete or partial response according to the Lugano Lymphoma Response Criteria by 6 months; any eligible patient who begins treatment with the combination regimen will be included in the denominator when calculating the ORR. ORR will be reported with a 95% binomial exact confidence interval.

  At 6 months

Secondary Outcomes (4)

• Complete response (CR) (assessed by positron emission tomography)

  At 6 months

• Duration of response (DOR)

  Time 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 60 months

• Progression-free survival

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

• Patient reported outcomes (PROs)

  Up to 12 months

Other Outcomes (2)

• Biomarker analyses

  Up to 60 months

• Pharmacokinetics analyses

  Up to 60 months

Study Arms (1)

Treatment (acalabrutinib, duvelisib)

EXPERIMENTAL

Patients receive acalabrutinib PO BID, and duvelisib PO BID on days 1-28. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 19, patients receive acalabrutinib PO BID for up to 60 months in absence of disease progression or unacceptable toxicity.

Drug: Acalabrutinib; Drug: Duvelisib

Interventions

Acalabrutinib DRUG

Given PO

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

Treatment (acalabrutinib, duvelisib)

Duvelisib DRUG

Given PO

Also known as: 8-Chloro-2-phenyl-3-((1S)-1-(7H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one, Copiktra, INK-1197, IPI-145

Treatment (acalabrutinib, duvelisib)

Eligibility Criteria

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

You may qualify if:

• \>= 18 years of age
• Histologically confirmed iNHL of any of the following subtypes recognized by the World Health Organization (WHO) classification: follicular lymphoma and marginal zone lymphoma (splenic, nodal and extranodal)
• Patients must meet clinical criteria for requiring treatment
• At least two prior systemic therapies for FL (phase 2 portion) and one prior systemic therapy for MZL. Prior autologous stem cell transplant is permitted. Prior CAR-T cell therapy is permitted. For the phase 1 portion, patients receiving one prior systemic therapy are allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Creatinine clearance \>= 50 ml/min using a 24-hour creatinine clearance or estimated creatinine clearance using the Cockcroft-Gault equation
• Bilirubin \< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 1.5 x ULN
• Absolute neutrophil count (ANC) \> 1000/mm\^3 (without growth factor support)
• Platelet \> 75,000/mm\^3 (without transfusion support)
• Unless related to bone marrow involvement with the disease, in which case platelets must be \> 50,000/mm\^3
• Hemoglobin \>= 8 gm/dL
• 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
• Radiographically measurable disease by computed tomography (CT) scan, defined as at least one node \> 1.5 cm in size or assessable disease

You may not qualify if:

• Prior exposure to a BCR inhibitor (e.g., BTK inhibitors, phosphoinositide-3 kinase \[PI3K\], or Syk inhibitors) or BCL-2 inhibitor
• Patients with grade 3B FL or clinical evidence of transformation to aggressive lymphoma
• Central nervous system (CNS) involvement
• 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 which will not limit survival to \< 1 year
• Clinically significant cardiovascular disease such as 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. Note: Subjects with controlled, asymptomatic atrial fibrillation can enroll in study
• Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists
• Prothrombin time (PT)/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of lupus anticoagulant) \> 2 x ULN
• 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
• Major surgical procedure within 28 days of the first dose of study drug. 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
• Pregnancy or lactation, or intending to become pregnant during the study
• Concurrent participation in another therapeutic clinical trial
• Known history of infection with human immunodeficiency virus (HIV)

Sponsors & Collaborators

• Narendranath Epperla: lead

Related Links

• The Jamesline

MeSH Terms

Conditions

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

Interventions

acalabrutinib; duvelisib

Condition Hierarchy (Ancestors)

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

Study Officials

• Narendranath Epperla, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 9, 2021
• First Posted: April 8, 2021
• Study Start: July 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: June 7, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share