Acalabrutinib (ACP-196), a Btk Inhibitor, for Treatment of de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma

• Sponsor: Acerta Pharma BV (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02112526
• Collaborator: (none)
• Enrollment: 21
• Locations: 7
• Arm: 1
• Anticipated Duration (Months): 136.8
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To characterize the safety profile of acalabrutinib in subjects with relapsed or refractory de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma (DLBCL).

Condition or Disease	Intervention/Treatment	Phase
Activated B-cell Diffuse Large B-Cell Lymphoma (ABC DLBCL)	Drug: Acalabrutinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Phase 1b Study of ACP 196 in Subjects With Relapsed or Refractory de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma
• Actual Study Start Date: Aug 7, 2014
• Actual Primary Completion Date: Jun 30, 2020
• Anticipated Study Completion Date: Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acalabrutinib	Drug: Acalabrutinib; Other Names: ACP-196

Outcome Measures

Primary Outcome Measures

1. Safety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL. [SAEs collected from time of consent; TEAEs beginning after first dose and continuing through 30 days (+/- 7 days) after last dose.]

   Safety assessments included SAEs TEAEs, including AEs leading to discontinuation of study drug or dose reduction.

Secondary Outcome Measures

1. Area Under the Plasma Concentration (AUC) [1 Cycle (28 days)]

   To Characterize the Pharmacokinetic parameter AUC of acalabrutinib

2. Maximum Observed Plasma Concentration (Cmax) [1 Cycle (28 days)]

   To Characterize the Pharmacokinetic parameter Cmax of acalabrutinib

3. Evaluate Pharmacodynamic (PD) Effects (Done at US Sites Only) [2 Cycles (1 cycle = 28 days) and at end of treatment]

   To evaluate the concentration pharmacodynamic effects of acalabrutinib

4. Evaluate Activity of Acalabrutinib as Measured by Overall Response Rate (ORR) [From enrollment to the date of disease progression, assessed up to Cycle 48 (1 cycle is 28 days)]

   To evaluate the activity of acalabrutinib as measured by ORR

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 130 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women ≥ 18 years of age.

• Pathologically confirmed de novo ABC DLBCL

• Relapsed or refractory disease

• Subjects must have ≥ 1 measurable disease sites

Exclusion Criteria:

• 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 LVEF < 50%

• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

• Breast feeding or pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Los Angeles	California	United States	90095
2	Research Site	Atlanta	Georgia	United States	30322
3	Research Site	New York	New York	United States	10021
4	Research Site	Columbus	Ohio	United States	43210
5	Research Site	Houston	Texas	United States	77030
6	Research Site	Leicester		United Kingdom	LE1 7RH
7	Research Site	Plymouth		United Kingdom	PL6 8DH

Sponsors and Collaborators

• Acerta Pharma BV

Investigators

• Study Director: AstraZeneca Clinical Trials, 1-877-240-9479; [e-mail]

Study Documents (Full-Text)

• Study Protocol - Mar 16, 2020
• Statistical Analysis Plan - Mar 20, 2018

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Acerta Pharma BV
• ClinicalTrials.gov Identifier: NCT02112526
• Other Study ID Numbers: ACE-LY-002
• First Posted: Apr 14, 2014
• Last Update Posted: Jun 10, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Acerta Pharma BV: de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma; Diffuse Large B-Cell Lymphoma; de Novo Activated B-cell (ABC); de Novo Activated B-cell; ABC DLBCL; DLBCL; Lymphoma; B-Cell; Immunoproliferative Disorders; Immune System Diseases; Bruton's tyrosine kinase
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Acalabrutinib

Study Results

Participant Flow

Arm/Group Title	Cohort 1 - Relapse Subjects	Cohort 2 - Refractory Subjects
Arm/Group Description	Acalabrutinib 100mg administered orally (PO) twice daily (BID)	Acalabrutinib 100mg administered orally (PO) twice daily (BID)
Period Title: Overall Study
STARTED	11	10
Enrolled	11	10
Received Study Medication	11	10
Discontinued Study	11	9
Subjects Continuing Study Medication	0	1
COMPLETED	0	1
NOT COMPLETED	11	9

Baseline Characteristics

Arm/Group Title	Cohort 1 - Relapse Subjects	Cohort 2 - Refractory Subjects	Total
Arm/Group Description	Acalabrutinib 100mg administered orally (PO) twice daily (BID)	Acalabrutinib 100mg administered orally (PO) twice daily (BID)	Total of all reporting groups
Overall Participants	11	10	21
Age (Year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Year]	70.7 (9.57)	56.9 (16.26)	64.1 (14.66)
Sex: Female, Male (Count of Participants)
Female	6 54.5%	5 50%	11 52.4%
Male	5 45.5%	5 50%	10 47.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 9.1%	1 10%	2 9.5%
Not Hispanic or Latino	10 90.9%	9 90%	19 90.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 9.1%	1 10%	2 9.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 10%	1 4.8%
White	10 90.9%	5 50%	15 71.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	3 30%	3 14.3%
Region of Enrollment (Count of Participants)
United States	9 81.8%	6 60%	15 71.4%
United Kingdom	2 18.2%	4 40%	6 28.6%

Outcome Measures

1. Primary Outcome

Title	Safety Profile of Acalabrutinib in Subjects With Relapsed or Refractory ABC DLBCL.
Description	Safety assessments included SAEs TEAEs, including AEs leading to discontinuation of study drug or dose reduction.
Time Frame	SAEs collected from time of consent; TEAEs beginning after first dose and continuing through 30 days (+/- 7 days) after last dose.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1 - Relapse Subjects	Cohort 2 - Refractory Subjects
Arm/Group Description	Acalabrutinib 100mg administered orally (PO) twice daily (BID)	Acalabrutinib 100mg administered orally (PO) twice daily (BID)
Measure Participants	11	10
Count of Participants [Participants]	3 27.3%	2 20%

2. Secondary Outcome

Title	Area Under the Plasma Concentration (AUC)
Description	To Characterize the Pharmacokinetic parameter AUC of acalabrutinib
Time Frame	1 Cycle (28 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	To Characterize the Pharmacokinetic parameter Cmax of acalabrutinib
Time Frame	1 Cycle (28 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Evaluate Pharmacodynamic (PD) Effects (Done at US Sites Only)
Description	To evaluate the concentration pharmacodynamic effects of acalabrutinib
Time Frame	2 Cycles (1 cycle = 28 days) and at end of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Evaluate Activity of Acalabrutinib as Measured by Overall Response Rate (ORR)
Description	To evaluate the activity of acalabrutinib as measured by ORR
Time Frame	From enrollment to the date of disease progression, assessed up to Cycle 48 (1 cycle is 28 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 697
Arm/Group Title	Cohort 1 - Relapse Subjects		Cohort 2 - Refractory Subjects
Arm/Group Description	Acalabrutinib 100mg administered orally (PO) twice daily		Acalabrutinib 100mg administered orally (PO) twice daily
All Cause Mortality
	Cohort 1 - Relapse Subjects		Cohort 2 - Refractory Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		5/10 (50%)
Serious Adverse Events
	Cohort 1 - Relapse Subjects		Cohort 2 - Refractory Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/11 (36.4%)		5/10 (50%)
Gastrointestinal disorders
Abdominal pain	0/11 (0%)		2/10 (20%)
General disorders
Pyrexia	1/11 (9.1%)		1/10 (10%)
Disease progression	1/11 (9.1%)		0/10 (0%)
Fatigue	0/11 (0%)		1/10 (10%)
Infections and infestations
Pneumonia	0/11 (0%)		1/10 (10%)
Septic shock	1/11 (9.1%)		0/10 (0%)
Viral infection	0/11 (0%)		1/10 (10%)
Investigations
Influenza B virus test positive	1/11 (9.1%)		0/10 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/11 (0%)		1/10 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to meninges	1/11 (9.1%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/11 (9.1%)		1/10 (10%)
Skin and subcutaneous tissue disorders
Skin necrosis	0/11 (0%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	Cohort 1 - Relapse Subjects		Cohort 2 - Refractory Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/11 (90.9%)		10/10 (100%)
Blood and lymphatic system disorders
Anaemia	2/11 (18.2%)		4/10 (40%)
Increased tendency to bruise	1/11 (9.1%)		0/10 (0%)
Cardiac disorders
Mitral valve incompetence	1/11 (9.1%)		0/10 (0%)
Ear and labyrinth disorders
Vertigo	1/11 (9.1%)		0/10 (0%)
Endocrine disorders
Adrenal insufficiency	1/11 (9.1%)		0/10 (0%)
Eye disorders
Conjunctival hyperaemia	1/11 (9.1%)		0/10 (0%)
Dry eye	1/11 (9.1%)		0/10 (0%)
Ocular hyperaemia	1/11 (9.1%)		0/10 (0%)
Gastrointestinal disorders
Diarrhoea	8/11 (72.7%)		1/10 (10%)
Nausea	2/11 (18.2%)		3/10 (30%)
Constipation	4/11 (36.4%)		0/10 (0%)
Vomiting	0/11 (0%)		2/10 (20%)
Abdominal distension	1/11 (9.1%)		0/10 (0%)
Abdominal pain	0/11 (0%)		1/10 (10%)
Abdominal pain upper	1/11 (9.1%)		0/10 (0%)
Ascites	0/11 (0%)		1/10 (10%)
Dysphagia	0/11 (0%)		1/10 (10%)
Faeces discoloured	1/11 (9.1%)		0/10 (0%)
Flatulence	1/11 (9.1%)		0/10 (0%)
Gastrooesophageal reflux disease	1/11 (9.1%)		0/10 (0%)
Stomatitis	1/11 (9.1%)		0/10 (0%)
General disorders
Fatigue	4/11 (36.4%)		4/10 (40%)
Oedema peripheral	2/11 (18.2%)		2/10 (20%)
Gait disturbance	2/11 (18.2%)		0/10 (0%)
Pyrexia	2/11 (18.2%)		0/10 (0%)
Axillary pain	0/11 (0%)		1/10 (10%)
Chest discomfort	0/11 (0%)		1/10 (10%)
Chills	0/11 (0%)		1/10 (10%)
Injection site bruising	1/11 (9.1%)		0/10 (0%)
Injection site rash	0/11 (0%)		1/10 (10%)
Mucosal inflammation	1/11 (9.1%)		0/10 (0%)
Oedema	1/11 (9.1%)		0/10 (0%)
Peripheral swelling	0/11 (0%)		1/10 (10%)
Hepatobiliary disorders
Cholecystitis	1/11 (9.1%)		0/10 (0%)
Immune system disorders
Contrast media allergy	1/11 (9.1%)		0/10 (0%)
Infections and infestations
Nasopharyngitis	1/11 (9.1%)		1/10 (10%)
Oral candidiasis	1/11 (9.1%)		1/10 (10%)
Sinusitis	1/11 (9.1%)		1/10 (10%)
Cellulitis	0/11 (0%)		1/10 (10%)
Lower respiratory tract infection fungal	1/11 (9.1%)		0/10 (0%)
Oral herpes	1/11 (9.1%)		0/10 (0%)
Rhinitis	0/11 (0%)		1/10 (10%)
Rhinovirus infection	1/11 (9.1%)		0/10 (0%)
Staphylococcal infection	1/11 (9.1%)		0/10 (0%)
Urinary tract infection	1/11 (9.1%)		0/10 (0%)
Urinary tract infection staphylococcal	1/11 (9.1%)		0/10 (0%)
Injury, poisoning and procedural complications
Contusion	2/11 (18.2%)		0/10 (0%)
Ear abrasion	0/11 (0%)		1/10 (10%)
Fall	0/11 (0%)		1/10 (10%)
Procedural pain	0/11 (0%)		1/10 (10%)
Skin abrasion	0/11 (0%)		1/10 (10%)
Investigations
Breath sounds abnormal	1/11 (9.1%)		0/10 (0%)
C-reactive protein increased	0/11 (0%)		1/10 (10%)
Cardiac murmur	0/11 (0%)		1/10 (10%)
Weight decreased	0/11 (0%)		1/10 (10%)
Metabolism and nutrition disorders
Decreased appetite	1/11 (9.1%)		2/10 (20%)
Dehydration	1/11 (9.1%)		2/10 (20%)
Hypokalaemia	2/11 (18.2%)		1/10 (10%)
Hypomagnesaemia	1/11 (9.1%)		1/10 (10%)
Hypocalcaemia	1/11 (9.1%)		0/10 (0%)
Hyponatraemia	0/11 (0%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/11 (9.1%)		2/10 (20%)
Back Pain	2/11 (18.2%)		0/10 (0%)
Musculoskeletal pain	0/11 (0%)		2/10 (20%)
Neck pain	1/11 (9.1%)		1/10 (10%)
Pain in extremity	0/11 (0%)		2/10 (20%)
Muscular weakness	0/11 (0%)		1/10 (10%)
Musculoskeletal chest pain	0/11 (0%)		1/10 (10%)
Myalgia	1/11 (9.1%)		0/10 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/11 (0%)		1/10 (10%)
Nervous system disorders
Dizziness	5/11 (45.5%)		1/10 (10%)
Headache	3/11 (27.3%)		2/10 (20%)
Carpal tunnel syndrome	1/11 (9.1%)		0/10 (0%)
Memory impairment	1/11 (9.1%)		0/10 (0%)
Neuropathy peripheral	1/11 (9.1%)		0/10 (0%)
Paraesthesia	0/11 (0%)		1/10 (10%)
Peripheral sensory neuropathy	0/11 (0%)		1/10 (10%)
Syncope	1/11 (9.1%)		0/10 (0%)
Psychiatric disorders
Insomnia	2/11 (18.2%)		0/10 (0%)
Depression	0/11 (0%)		1/10 (10%)
Mental status changes	1/11 (9.1%)		0/10 (0%)
Renal and urinary disorders
Urinary retention disorders	1/11 (9.1%)		0/10 (0%)
Reproductive system and breast disorders
Breast swelling	0/11 (0%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	3/11 (27.3%)		3/10 (30%)
Dyspnoea	2/11 (18.2%)		2/10 (20%)
Pleural effusion	1/11 (9.1%)		1/10 (10%)
Rales	1/11 (9.1%)		1/10 (10%)
Dysphonia	0/11 (0%)		1/10 (10%)
Nasal congestion	0/11 (0%)		1/10 (10%)
Productive cough	0/11 (0%)		1/10 (10%)
throat irritation	0/11 (0%)		1/10 (10%)
Wheezing	1/11 (9.1%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/11 (0%)		2/10 (20%)
Ecchymosis	1/11 (9.1%)		1/10 (10%)
Petechiae	1/11 (9.1%)		1/10 (10%)
Rash	2/11 (18.2%)		0/10 (0%)
Actinic Keratosis	1/11 (9.1%)		0/10 (0%)
Erythema	0/11 (0%)		1/10 (10%)
Night sweats	1/11 (9.1%)		0/10 (0%)
Pruritus	0/11 (0%)		1/10 (10%)
Rash maculo-papular	1/11 (9.1%)		0/10 (0%)
Rosacea	1/11 (9.1%)		0/10 (0%)
Skin necrosis	0/11 (0%)		1/10 (10%)
Vascular disorders
Orthostatic hypotension	1/11 (9.1%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS 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.