HEPLISAV-B Hepatitis B Vaccine in Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's-Tyrosine Kinase Inhibitor (BTK-I)

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03685708
• Collaborator: (none)
• Enrollment: 78
• Location: 1
• Arms: 3
• Actual Duration (Months): 24.3
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

Background:

People with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) tend to get infections more easily. This is because their immune systems are weakened. Hepatitis B is a virus that can be transmitted when body fluids from an infected person enter the body of an uninfected person. This virus can be dangerous for people with leukemia and lymphoma. HEPLISAV-B is a new hepatitis B vaccine. Researchers want to see if it can protect people with CLL/SLL from getting hepatitis B.

Objective:

To learn how HEPLISAV-B works in people who have CLL or SLL.

Eligibility:

Adults 18 years and older with CLL (or SLL). They must be getting no treatment for their CLL, or getting ibrutinib or acalabrutinib for it.

Design:

This study lasts 6 months from the date of first vaccination.

Participants may be screened with:

Physical exam

Blood tests

Pregnancy test

Visit 1

Participants will get blood drawn and the study vaccine. It will be given as an injection. If they get any symptoms within 7 days of the vaccine, they will write them in a diary.

Visit 2

After 3 months, participants will come back to the NIH to get another blood draw and the second vaccine dose.

Visit 3

Participants will return 3 months after the second vaccine dose was given. They will have blood drawn.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis; Safety and Tolerability	Biological: HEPLISAV-B	Phase 2

Detailed Description

This study aims to determine the HEPLISAV-B hepatitis B vaccine efficacy in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) lymphocytic patients that are treatment naive or receiving Bruton s-tyrosine kinase inhibitor (BTK-I) therapy. (Note: Since CLL and SLL are considered the same disease, CLL/SLL will be referred to as CLL hereafter, unless otherwise specified).

Key Eligibility Criteria:

1. Diagnosis of CLL

2. Cohort 1: Treatment naive CLL or SLL patients

3. Cohort 2: Subjects must be receiving ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose

4. Cohort 3: Subjects must be receiving acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose

5. No known active or past hepatitis B infection

6. No history of prior hepatitis B virus vaccination (approved or investigational)

7. Age greater greater than or equal to 18 years.

8. ECOG performance status of 0-1

Design:

Patients with CLL will enroll on the study for the purpose of determining the HEPLISAV-B vaccine efficacy in patients who are treatment naive ore receiving BTK-I therapy. A series of 2 doses of HEPLISAV-B will be given on a 0- and 3- month schedule by intramuscular injection. Subjects will be followed at regular intervals and receive serologic response assessment following completion of the HEPLISAV-B vaccine series (6 months after the first vaccine

administration).

Study Objectives:

Primary Objective:

1. Determine the rate of hepatitis B seroprotective titer achievement (anti-HBs greater than or equal to 10mIU/mL) following completion of the HEPLISAV-B 2-dose vaccine series (6 months after the first vaccine administration) in the following populations:

• CLL patients who are treatment naive (n=54)

• CLL patients receiving treatment with ibrutinib (n=27)

• CLL patients receiving treatment with acalabrutinib (n=27)

Secondary Objective:

1. Determine the safety and tolerability of the HEPLISAV-B vaccine among CLL patients who are treatment naive or receiving BTK-Is (ibrutinib or acalabrutinib).

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Response to the HEPLISAV-B Hepatitis B Vaccine in Treatment Naive Chronic Lymphocytic Leukemia (CLL) and CLL Treated With Bruton's -Tyrosine Kinase Inhibitor (BTK-I)
• Actual Study Start Date: Dec 7, 2018
• Actual Primary Completion Date: Dec 16, 2020
• Actual Study Completion Date: Dec 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve Treatment naïve Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL) patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Biological: HEPLISAV-B; HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.
Experimental: Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib Ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Biological: HEPLISAV-B; HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.
Experimental: Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib Acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Biological: HEPLISAV-B; HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With HEPLISAV-B Seroprotective Titer (Anti-HBs 10mIU/mL) [6 months after the first vaccine administration]

   Determine the rate of hepatitis B seroprotective titer achievement (anti-HBs 10mIU/mL) following completion of the HEPLISAV-B 2-dose vaccine series (6 months after the first vaccine administration) among chronic lymphocytic leukemia (CLL) patients who are treatment naïve or receiving Bruton Tyrosine Kinase (BTK) inhibitors (Ibrutinib or Acalabrutinib).

Secondary Outcome Measures

1. Number of Participants That Experienced Serious Adverse Events Following HEPLISAV-B Vaccine Among CLL Patients [6 months after the first vaccine administration]

   Determine the safety of the HEPLISAV-B vaccine among chronic lymphocytic leukemia (CLL) patients who are treatment naïve or receiving Bruton Tyrosine Kinase (BTK) inhibitors (Ibrutinib or Acalabrutinib).

2. Number of Participants That Did Not Complete Study Due to Intolerance of the HEPLISAV-B Vaccine Among CLL Patients. [6 months after the first vaccine administration]

   Determine the tolerability of the HEPLISAV-B vaccine among chronic lymphocytic leukemia (CLL) patients who are treatment naïve or receiving Bruton Tyrosine Kinase (BTK) inhibitors (Ibrutinib or Acalabrutinib).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• INCLUSION CRITERIA:

• Diagnosis of CLL/SLL which is made according to the updated criteria of the NCI Working Group.

• No known active or past hepatitis B infection

• No history of prior hepatitis B virus vaccination (approved or investigational)

• History of negative hepatitis B viral titers (negative HBsAg, HBsAb and HBcAb)

• Cohort 1: Treatment naive CLL patients

• Cohort 2: Subjects must be receiving ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose

• Cohort 3: Subjects must be receiving acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose

• Age greater than or equal to 18 years.

• ECOG performance status of 0-1

• Able to comprehend the investigational nature of the protocol and provide informed consent.

EXCLUSION CRITERIA:

• Female patients who are currently pregnant.

• Any uncontrolled active systemic infection

• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator s opinion, could compromise the subject s safety or put the study outcomes at undue risk

• History of severe allergic reaction to any component of HEPLISAV-B, including yeast

• Receive intravenous or subcutaneous immunoglobulin (IVIG) within 3 months prior to vaccination

• Concomitant use of immunosuppressive agents (e.g. steroids, radiotherapy, chemotherapy)

• Hereditary or acquired immunodeficiency syndrome unrelated to CLL

• Non-English speaking individuals will be excluded from the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Christopher MT Pleyer, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 20, 2020

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT03685708
• Other Study ID Numbers: 180145; 18-H-0145
• First Posted: Sep 26, 2018
• Last Update Posted: Feb 8, 2022
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): Ibrutinib; Acalabrutinib; Immunology
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hepatitis

Study Results

Participant Flow

Recruitment Details	A total of 78 participants were assessed for eligibility and consented. 76 participants met eligibility criteria.

Arm/Group Title	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib	Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve
Arm/Group Description	Acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Treatment naïve Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL) patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.
Period Title: Overall Study
STARTED	14	18	46
COMPLETED	13	16	37
NOT COMPLETED	1	2	9

Baseline Characteristics

Arm/Group Title	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib	Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve	Total
Arm/Group Description	Acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Treatment naïve Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL) patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Total of all reporting groups
Overall Participants	14	18	46	78
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	9 64.3%	6 33.3%	22 47.8%	37 47.4%
>=65 years	5 35.7%	12 66.7%	24 52.2%	41 52.6%
Sex: Female, Male (Count of Participants)
Female	3 21.4%	6 33.3%	20 43.5%	29 37.2%
Male	11 78.6%	12 66.7%	26 56.5%	49 62.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 5.6%	2 4.3%	3 3.8%
Not Hispanic or Latino	14 100%	17 94.4%	43 93.5%	74 94.9%
Unknown or Not Reported	0 0%	0 0%	1 2.2%	1 1.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 2.2%	1 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 7.1%	0 0%	2 4.3%	3 3.8%
White	12 85.7%	17 94.4%	42 91.3%	71 91%
More than one race	1 7.1%	1 5.6%	1 2.2%	3 3.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With HEPLISAV-B Seroprotective Titer (Anti-HBs 10mIU/mL)
Description	Determine the rate of hepatitis B seroprotective titer achievement (anti-HBs 10mIU/mL) following completion of the HEPLISAV-B 2-dose vaccine series (6 months after the first vaccine administration) among chronic lymphocytic leukemia (CLL) patients who are treatment naïve or receiving Bruton Tyrosine Kinase (BTK) inhibitors (Ibrutinib or Acalabrutinib).
Time Frame	6 months after the first vaccine administration

Outcome Measure Data

Analysis Population Description

All participants that completed the 2 doses vaccine series and blood draws. 8 participants could not complete laboratory assessments due to COVID pandemic.

Arm/Group Title	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib	Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve
Arm/Group Description	Acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Treatment naïve Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL) patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.
Measure Participants	11	15	32
Count of Participants [Participants]	0 0%	1 5.6%	9 19.6%

2. Secondary Outcome

Title	Number of Participants That Experienced Serious Adverse Events Following HEPLISAV-B Vaccine Among CLL Patients
Description	Determine the safety of the HEPLISAV-B vaccine among chronic lymphocytic leukemia (CLL) patients who are treatment naïve or receiving Bruton Tyrosine Kinase (BTK) inhibitors (Ibrutinib or Acalabrutinib).
Time Frame	6 months after the first vaccine administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib	Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve
Arm/Group Description	Acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Treatment naïve Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL) patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.
Measure Participants	14	18	46
Count of Participants [Participants]	0 0%	0 0%	1 2.2%

3. Secondary Outcome

Title	Number of Participants That Did Not Complete Study Due to Intolerance of the HEPLISAV-B Vaccine Among CLL Patients.
Description	Determine the tolerability of the HEPLISAV-B vaccine among chronic lymphocytic leukemia (CLL) patients who are treatment naïve or receiving Bruton Tyrosine Kinase (BTK) inhibitors (Ibrutinib or Acalabrutinib).
Time Frame	6 months after the first vaccine administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib	Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve
Arm/Group Description	Acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.	Treatment naïve Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL) patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.
Measure Participants	14	18	46
Count of Participants [Participants]	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Events will be collected for 7 days following the first and second vaccine dose and followed until resolution
Adverse Event Reporting Description	All events whether volunteered by the subject, discovered by study personnel during questioning, or detected through physical examination, clinically significant laboratory test, or other means will be recorded.
Arm/Group Title	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib		Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib		Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve
Arm/Group Description	Acalabrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.		Ibrutinib monotherapy for at least 6 months prior to administration of the first vaccine dose in patients with Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.		Treatment naïve Chronic Lymphocytic Leukemia (CLL) or small lymphocytic lymphoma (SLL) patients will receive HEPLISAV-B (Hepatitis B Vaccine [Recombinant ], adjuvanted) vaccine - A series of 2 doses (0.5 ml each) will be given on a 0- and 3- month schedule via intramuscular injection.
All Cause Mortality
	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib		Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib		Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/18 (0%)		0/46 (0%)
Serious Adverse Events
	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib		Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib		Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/18 (0%)		1/46 (2.2%)
Infections and infestations
Lung infection	0/14 (0%)	0	0/18 (0%)	0	1/46 (2.2%)	1
Other (Not Including Serious) Adverse Events
	Chronic Lymphocytic Leukemia Patients Receiving Treatment With Acalabrutinib		Chronic Lymphocytic Leukemia Patients Receiving Treatment With Ibrutinib		Chronic Lymphocytic Leukemia Patients That Are Treatment Naïve
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/14 (85.7%)		17/18 (94.4%)		40/46 (87%)
Blood and lymphatic system disorders
Lymph node pain	0/14 (0%)	0	1/18 (5.6%)	1	0/46 (0%)	0
Gastrointestinal disorders
Dyspepsia	1/14 (7.1%)	1	0/18 (0%)	0	0/46 (0%)	0
Mucositis oral	1/14 (7.1%)	1	0/18 (0%)	0	0/46 (0%)	0
Nausea	0/14 (0%)	0	2/18 (11.1%)	2	0/46 (0%)	0
Nausea	0/14 (0%)	0	0/18 (0%)	0	7/46 (15.2%)	7
General disorders
Chills	2/14 (14.3%)	2	1/18 (5.6%)	1	9/46 (19.6%)	12
Edema limbs	3/14 (21.4%)	3	2/18 (11.1%)	4	10/46 (21.7%)	11
Fatigue	5/14 (35.7%)	11	8/18 (44.4%)	13	20/46 (43.5%)	36
Flu like symptoms	2/14 (14.3%)	4	0/18 (0%)	0	11/46 (23.9%)	19
Injection site reaction	2/14 (14.3%)	2	7/18 (38.9%)	9	8/46 (17.4%)	13
Pain	12/14 (85.7%)	32	16/18 (88.9%)	32	35/46 (76.1%)	98
Vaccination site lymphadenopathy	0/14 (0%)	0	2/18 (11.1%)	2	0/46 (0%)	0
Fever	0/14 (0%)	0	0/18 (0%)	0	4/46 (8.7%)	5
Vaccination site lymphadenopathy	0/14 (0%)	0	0/18 (0%)	0	4/46 (8.7%)	6
Infections and infestations
Conjunctivitis	0/14 (0%)	0	1/18 (5.6%)	1	0/46 (0%)	0
Injury, poisoning and procedural complications
Bruising	1/14 (7.1%)	3	3/18 (16.7%)	3	0/46 (0%)	0
Bruising	0/14 (0%)	0	0/18 (0%)	0	3/46 (6.5%)	3
Musculoskeletal and connective tissue disorders
Muscle cramp	1/14 (7.1%)	1	0/18 (0%)	0	0/46 (0%)	0
Myalgia	6/14 (42.9%)	10	5/18 (27.8%)	9	19/46 (41.3%)	30
Neck pain	0/14 (0%)	0	1/18 (5.6%)	1	0/46 (0%)	0
Nervous system disorders
Syncope	1/14 (7.1%)	1	0/18 (0%)	0	0/46 (0%)	0
Dizziness	0/14 (0%)	0	1/18 (5.6%)	1	0/46 (0%)	0
Headache	2/14 (14.3%)	2	7/18 (38.9%)	8	2/46 (4.3%)	2
Neuralgia	0/14 (0%)	0	1/18 (5.6%)	1	0/46 (0%)	0
Dizziness	0/14 (0%)	0	0/18 (0%)	0	3/46 (6.5%)	3
Headache	0/14 (0%)	0	0/18 (0%)	0	22/46 (47.8%)	35
Respiratory, thoracic and mediastinal disorders
Sore throat	1/14 (7.1%)	1	0/18 (0%)	0	0/46 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/14 (0%)	0	1/18 (5.6%)	1	0/46 (0%)	0
Rash maculo-papular	3/14 (21.4%)	6	8/18 (44.4%)	12	20/46 (43.5%)	26
Pruritus	0/14 (0%)	0	0/18 (0%)	0	5/46 (10.9%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.