Ibrutinib as an Immune Modulating Agent for Patients With Asymptomatic, High-risk CLL/SLL Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT02518555 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-15012NCI-2015-00932
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial studies how well ibrutinib works when given together with vaccine therapies in treating patients without clinical signs or indications that raise the possibility of a particular disorder or dysfunction (asymptomatic) who have high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Vaccines, such as pneumococcal 13-valent conjugate vaccine, trivalent influenza vaccine, and diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine adsorbed, may help the body build an effective immune response to kill cancer cells. Giving ibrutinib together with vaccine therapies may be a better treatment for chronic lymphocytic leukemia or small lymphocytic lymphoma.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who are alive and progression-free

  At 2 years from the date of the first ibrutinib administration

Secondary Outcomes (5)

• Degree of response (CR MRD-,CR, PR, PR with lymphocytosis, and SD)

  Up to 4 years

• Incidence of adverse events, evaluated using the NCI CTCAE version 4.0

  Up to 30 days after study treatment

• Proportion of patients who achieve complete response

  Within 2 years of starting ibrutinib treatment

• Time to next treatment

  Date of first ibrutinib therapy until the date of next treatment, assessed up to 4 years

• Time to treatment failure

  Date of first ibrutinib therapy until the date of next treatment, date of death, or date off-study if due to toxicity, whichever occurs first, assessed up to 4 years

Study Arms (2)

Arm A (concurrent vaccines and ibrutinib)

EXPERIMENTAL

Patients receive ibrutinib PO QD on days 1-28. Patients also receive pneumococcal 13-valent conjugate vaccine IM on day 1 of courses 3 and 5 and trivalent influenza vaccine IM and DTaP vaccine IM on day 1 of course 4. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Biological: Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed; Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Pneumococcal 13-valent Conjugate Vaccine; Other: Quality-of-Life Assessment; Biological: Trivalent Influenza Vaccine

Arm B (sequential vaccines and ibrutinib)

EXPERIMENTAL

Patients receive pneumococcal 13-valent conjugate vaccine IM on day 1 of courses 1 and 3 and trivalent influenza IM and DTaP vaccine IM on day 1 of course 2. Beginning in course 4, patients receive ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.

Biological: Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed; Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Pneumococcal 13-valent Conjugate Vaccine; Other: Quality-of-Life Assessment; Biological: Trivalent Influenza Vaccine

Interventions

Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed BIOLOGICAL

Given IM

Also known as: Adacel, Daptacel, Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine, DTaP

Arm A (concurrent vaccines and ibrutinib); Arm B (sequential vaccines and ibrutinib)

Ibrutinib DRUG

Given PO

Also known as: PCI-32765

Arm A (concurrent vaccines and ibrutinib); Arm B (sequential vaccines and ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (concurrent vaccines and ibrutinib); Arm B (sequential vaccines and ibrutinib)

Pharmacological Study OTHER

Correlative studies

Arm A (concurrent vaccines and ibrutinib); Arm B (sequential vaccines and ibrutinib)

Pneumococcal 13-valent Conjugate Vaccine BIOLOGICAL

Given IM

Also known as: PCV13 Vaccine, Prevnar 13

Arm A (concurrent vaccines and ibrutinib); Arm B (sequential vaccines and ibrutinib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (concurrent vaccines and ibrutinib); Arm B (sequential vaccines and ibrutinib)

Trivalent Influenza Vaccine BIOLOGICAL

Given IM

Also known as: Flu prevention, Flu prophylaxis, Flu shot, Flu vaccination, Fluarix, Fluzone, Influenza Vaccine, Influenza Virus Vaccine, Trivalent, Types A and B, TIV

Arm A (concurrent vaccines and ibrutinib); Arm B (sequential vaccines and ibrutinib)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically identified chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) as defined by the World Health Organization (WHO) classification of hematopoietic neoplasms
• CLL/SLL cells must demonstrate one or more of the following high-risk genomic features:
• Del17p13.1(tumor protein p53 \[TP53\]) as detected by fluorescence in-situ hybridization (FISH)
• Del11q22.3 ataxia telangiectasia mutated (ATM) as detected by FISH
• Complex karyotype (\>= 3 cytogenetic abnormalities on stimulated karyotype)
• Unmutated immunoglobulin variable region heavy chain (IgVH) ( \>= 98% sequence homology compared with germline sequence)
• Zeta-chain (TCR) associated protein kinase 70kDa (ZAP-70) gene promoter hypomethylation \< 20%
• No prior therapy for CLL/SLL, including chemotherapy and/or radiotherapy is allowed
• Estimated life expectancy of greater than 24 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Total bilirubin =\< 1.5X upper limit of normal (ULN) unless secondary to Gilbert's disease
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5X institutional upper limit of normal
• Serum creatinine =\< 2 md/dL or estimated creatinine clearance (CrCl) \> 50ml/min/body surface area (BSA)
• Prothrombin time (PT)/international normalized ratio (INR) \< 1.5 x ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time \[aPTT\]) \< 1.5 x ULN
• Able to swallow capsules without difficulty and no history of malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or active ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction

You may not qualify if:

• Patients meeting any of the following consensus criteria for initiating treatment for their CLL:
• Progressive symptomatic splenomegaly and/or lymphadenopathy identified by physical examination
• Anemia ( \< 11g/dL) or thrombocytopenia ( \< 100,000/uL) due to bone marrow involvement
• Presence of unintentional weight loss \> 10% over the preceding 6 months
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade \>= 3 fatigue
• Fevers \> 100.5°F or night sweats for \> 2 weeks without evidence of infection
• Patients who have had any treatment for their CLL/SLL, including but not limited to chemotherapy, radiotherapy, or immunotherapy, prior to entering the study
• No corticosteroid use will be permitted within two weeks prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributable to compounds of similar chemical or biologic composition to ibrutinib or any component of pneumococcal, influenza and DTaP vaccines
• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject is considered by his or her physician to have a less than 2-year survival expectation
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection and/or psychiatric illness/social situations that would limit compliance with study requirements
• Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization
• Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration \[\> 14 days\] of \> 20mg/day of prednisone) within 14 days of the first dose of study drug
• Patients must discontinue treatment with H2-blockers (cimetidine, ranitidine, etc.) prior to beginning protocol therapy

Sponsors & Collaborators

• Jennifer Woyach: lead
• Pharmacyclics LLC.: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Arrato NA, Valentine TR, Byrd JC, Jones JA, Maddocks KJ, Woyach JA, Andersen BL. Illness representations and psychological outcomes in chronic lymphocytic leukaemia. Br J Health Psychol. 2022 May;27(2):553-570. doi: 10.1111/bjhp.12562. Epub 2021 Oct 4.

  PMID: 34608724 DERIVED

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Diphtheria Toxoid; adacel; Diphtheria-Tetanus-acellular Pertussis Vaccines; ibrutinib; 13-valent pneumococcal vaccine; Influenza Vaccines; fluarix

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

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures; Pertussis Vaccine; Bacterial Vaccines; Tetanus Toxoid; Vaccines, Combined; Vaccines, Acellular; Vaccines, Subunit; Viral Vaccines

Study Officials

• Jennifer Woyach, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 9, 2015
• First Posted: August 10, 2015
• Study Start: January 12, 2016
• Primary Completion: December 15, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)