Acalabrutinib in Patients With Relapsed/Refractory and Treatment naïve Deletion 17p CLL/SLL

NCT02337829 | Completed Phase 2 Results

• 1 other identifier: 15-H-0016
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to determine the response to acalabrutinib in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Relapsed/refractory CLL; Btk; Leukemia; Lymphocytic; Lymphoma; Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); ACP-196; Acalabrutinib; Treatment naive CLL; 17p deletion; TP53 mutation; NOTCH1 mutation

Outcome Measures

Primary Outcomes (1)

• Response Based on Overall Response Rate

  The best response to treatment was determined according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria incorporating 2012 and 2013 clarifications pertaining to subjects treated with kinase inhibitors. Overall response rate (ORR) was the proportion of subjects who achieved complete response (CR), CR with incomplete marrow recovery (CRi), or partial response (PR) while on treatment before the initiation of new anti-cancer therapy or stem cell transplant.

  Cycle 1 (28 Days) to 6 months

Study Arms (2)

Arm A

EXPERIMENTAL

Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.

Drug: Acalabrutinib (Arm A); Drug: Acalabrutinib (Arm B)

Arm B

EXPERIMENTAL

Subjects will be randomized to receive 1 of 2 dosing regimens: 1) acalabrutinib, dose A once daily; or 2) acalabrutinib, dose B twice daily.

Drug: Acalabrutinib (Arm A); Drug: Acalabrutinib (Arm B)

Interventions

Acalabrutinib (Arm A) DRUG

* A1a) acalabrutinib, dose A daily: biopsy (T) schedule W; * A1b) acalabrutinib, dose A daily: biopsy (T) schedule V. * A2a) acalabrutinib, dose B q 12 hours: biopsy (T) schedule Y; * A2b) acalabrutinib, dose B q 12 hours; biopsy (T) schedule Z

Also known as: ACP-196

Arm A; Arm B

Acalabrutinib (Arm B) DRUG

B1c) acalabrutinib, dose A daily: biopsy (U) schedule W; • B2c) acalabrutinib, dose B q12 hours: biopsy (U)) schedule Y.

Also known as: ACP-196

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• Men and women 18 years of age and older with histologically confirmed disease.
• Active disease as defined by at least one of the following (IWCLL consensus criteria):
• Weight loss ≥10% within the previous 6 months
• Extreme fatigue
• Fevers of greater than 100.5ºF for ≥2 weeks without evidence of infection
• Night sweats for more than one month without evidence of infection
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
• Massive or progressive splenomegaly
• Massive nodes or clusters or progressive lymphadenopathy
• Progressive lymphocytosis with an increase of \>50% over a 2 month period, or an anticipated doubling time of less than 6 months
• Compensated autoimmune hemolysis
• Relapsed/Refractory CLL or treatment naïve CLL patients with 17p deletion, TP53 mutation, or NOTCH1 mutation
• Agreement to use acceptable methods of contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear or beget children.
• Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty and serial biopsies.
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).

You may not qualify if:

• Radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or investigational products in the last 4 weeks.
• Richter's transformation. Autoimmune hemolytic anemia or thrombocytopenia requiring steroid therapy. Impaired hepatic function

Sponsors & Collaborators

• Acerta Pharma BV: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Research Site

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Alsadhan A, Chen J, Gaglione EM, Underbayev C, Tuma PL, Tian X, Freeman LA, Baskar S, Nierman P, Soto S, Itsara A, Ahn IE, Sun C, Bibikova E, Hartmann TN, Mhibik M, Wiestner A. CD49d Expression Identifies a Biologically Distinct Subtype of Chronic Lymphocytic Leukemia with Inferior Progression-Free Survival on BTK Inhibitor Therapy. Clin Cancer Res. 2023 Sep 15;29(18):3612-3621. doi: 10.1158/1078-0432.CCR-22-3217.

  PMID: 37227160 DERIVED

• Cyr MG, Mhibik M, Qi J, Peng H, Chang J, Gaglione EM, Eik D, Herrick J, Venables T, Novick SJ, Courouble VV, Griffin PR, Wiestner A, Rader C. Patient-derived Siglec-6-targeting antibodies engineered for T-cell recruitment have potential therapeutic utility in chronic lymphocytic leukemia. J Immunother Cancer. 2022 Nov;10(11):e004850. doi: 10.1136/jitc-2022-004850.

  PMID: 36442911 DERIVED

• Sun C, Nierman P, Kendall EK, Cheung J, Gulrajani M, Herman SEM, Pleyer C, Ahn IE, Stetler-Stevenson M, Yuan CM, Maric I, Gaglione EM, Harris HM, Pittaluga S, Wang MH, Patel P, Farooqui MZH, Izumi R, Hamdy A, Covey T, Wiestner A. Clinical and biological implications of target occupancy in CLL treated with the BTK inhibitor acalabrutinib. Blood. 2020 Jul 2;136(1):93-105. doi: 10.1182/blood.2019003715.

  PMID: 32202637 DERIVED

• Alsadhan A, Cheung J, Gulrajani M, Gaglione EM, Nierman P, Hamdy A, Izumi R, Bibikova E, Patel P, Sun C, Covey T, Herman SEM, Wiestner A. Pharmacodynamic Analysis of BTK Inhibition in Patients with Chronic Lymphocytic Leukemia Treated with Acalabrutinib. Clin Cancer Res. 2020 Jun 15;26(12):2800-2809. doi: 10.1158/1078-0432.CCR-19-3505. Epub 2020 Feb 13.

  PMID: 32054731 DERIVED

Related Links

• 15-H-0016\_Protocol Redacted
• 15-H-0016\_SAP ed.3 Redacted

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence; Leukemia; Lymphoma; Chromosome 17 deletion

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; 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

Results Point of Contact

• Title: Acerta Clinical Trials
• Organization: Acerta Pharma B.V.

acertamc@dlss.com

1-888-292-9613

Study Officials

• AstraZeneca Clinical Study Information Center

  1-877-240-9479 - information.center@astrazeneca.com

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: January 14, 2015
• Study Start: January 12, 2015
• Primary Completion: June 26, 2020
• Study Completion: October 31, 2025
• Last Updated: January 8, 2026
• Results First Posted: August 18, 2021

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (1)