Daratumumab and Ibrutinib in Treating Patients With Symptomatic Chronic Lymphocytic Leukemia

NCT03447808 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-17143NCI-2018-00159
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trials studies the side effects of daratumumab and ibrutinib and how well they work in treating patients with symptomatic chronic lymphocytic leukemia. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving daratumumab and ibrutinib may work better in treating patients with chronic lymphocytic leukemia.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Complete response (CR) + complete response with incomplete marrow recovery (CRi) defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria

  Up to 2 years

• Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Will be tabulated by type and grade and displayed in summary form.

  Up to 2 years

Secondary Outcomes (4)

• Duration of response (DOR)

  From the date of first response until the date of progression or death presumed attributable to disease progression, whichever occurs first, assessed up to 2 years

• Overall survival

  From the first treatment date until the date of death or date last known alive, assessed up to 2 years

• Overall survival (CR + CRi + partial response [PR])

  Up to 2 years

• Progression-free survival

  From the first treatment date until the date of progression or death, whichever occurs first, assessed up to 2 years

Study Arms (1)

Treatment (daratumumab, ibrutinib)

EXPERIMENTAL

Patients receive daratumumab IV on days 1, 8, 15, and 22 of courses 1-2, days 1 and 15 of courses 3-6, and day 1 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Beginning course 2, patients also receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Daratumumab; Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Daratumumab BIOLOGICAL

Given IV

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Treatment (daratumumab, ibrutinib)

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (daratumumab, ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (daratumumab, ibrutinib)

Pharmacological Study OTHER

Correlative studies

Treatment (daratumumab, ibrutinib)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of chronic lymphocytic leukemia (CLL) meeting criteria established in the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for the diagnosis and treatment of CLL
• Requires therapy for symptomatic CLL in the opinion of the treating physician as defined by:
• Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
• Massive (\>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
• Massive nodes (\>= 10 cm) or progressive or symptomatic lymphadenopathy
• Constitutional symptoms, which include any of the following:
• Unintentional weight loss of 10% or more within 6 months
• Significant fatigue limiting activity
• Fevers \>= 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
• Night sweats \> 1 month without evidence of infection
• No prior chemotherapy, immunotherapy, or targeted therapy for the treatment of CLL with the exception of palliative loco-regional radiotherapy and corticosteroids for symptom control
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Hemoglobin \>= 8 g/dL
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelets \>= 30,000/mm\^3

You may not qualify if:

• Patients who have had chemotherapy, immunotherapy, radiotherapy, or investigational therapy within 28 days prior to entering the study or those who have not recovered from adverse events due to agents administered more than 28 days earlier; steroids for control of disease related symptoms are permitted
• Patients who are receiving any other investigational agents
• History of stroke or intracranial hemorrhage within 6 months prior to randomization
• Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
• Active Richter's transformation
• Known active involvement of the central nervous system by lymphoma or leukemia
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon); patients may be eligible if able to be taken off warfarin and started on an alternative anticoagulant
• Requires chronic treatment with strong CYP3A inhibitors
• Known infection with the human immunodeficiency virus (HIV) virus
• 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
• History of severe (defined as grade 4 and/or requiring permanent discontinuation of prior antibody therapy) allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies
• A female patient who is pregnant or breast-feeding
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \[FEV1\] \< 50% of predicted normal), persistent asthma, or a history of poorly controlled asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed)
• History of other active malignancies other than CLL within the past 3 years prior to study entry, with the exception of adequately treated in situ carcinoma or the cervix uteri or breast, basal cell or localized squamous cell carcinoma of the skin, previous malignancy confirmed and surgically resected (or treated with other modalities) with curative intent or without relapse for \>= 2 years

Sponsors & Collaborators

• Jennifer Woyach: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

daratumumab; ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jennifer Woyach, 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: February 21, 2018
• First Posted: February 27, 2018
• Study Start: August 16, 2018
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)