Clinical trial NCT02337829: Acalabrutinib in Patients With Relapsed/Refractory and Treatment naïve Deletion 17p CLL/SLL
Official title: A Phase II Study Using ACP-196 (Acalabrutinib) in Patients With Relapsed/Refractory and Treatment-naïve Deletion 17p CLL/SLL: Pharmacodynamic Assessment of BTK Inhibition and Antitumor Response.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Acerta Pharma BV
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
First posted: 2015-01-14
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: To investigate the safety and efficacy of acalabrutinib for patients with CLL/SLL that have relapsed/refractory disease or treatment naive deletion 17p.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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

Primary outcomes:
measure: Response Based on Overall Response Rate
timeFrame: Cycle 1 (28 Days) to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Research Site
state: Maryland
Study officials:
affiliation: 1-877-240-9479 - information.center@astrazeneca.com
name: AstraZeneca Clinical Study Information Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.