Clinical trial NCT02362035: ACP-196 (Acalabrutinib) in Combination With Pembrolizumab, for Treatment of Hematologic Malignancies
Official title: A Phase 1b/2 Proof-of-Concept Study of the Combination of ACP-196 (Acalabrutinib) and Pembrolizumab in Subjects With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Follicular Lymphoma (FL)
CLL
Small Lymphocytic Lymphoma (SLL)
Richter's Syndrome
Mantle Cell Lymphoma (MCL)
Indolent Non Hodgkin Lymphoma
Waldenström Macroglobulinemia
Multiple Myeloma
Hodgkin Lymphoma
Burkitt Lymphoma
Marginal Zone Lymphomas
Mediastinal Large B Cell Lymphoma
Hairy Cell Leukemia
Keywords: Bruton tyrosine kinase inhibitor
Btk
B-Cell Malignancies
Mantle Cell
Multiple Myeloma
CLL
SLL
DLBCL
Follicular
Waldenstrom
Burkitt lymphoma
marginal zone lymphomas
hairy cell leukemia
B cell acute lymphoid leukemia
Acalabrutinib
ACP-196
Lead sponsor: Acerta Pharma BV
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2015-02-12
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies.

Detailed description: This is a Phase 1b/2, open-label, nonrandomized study that will be conducted in 2 stages. In the first stage, Part 1 of the study will determine the safety and preliminary efficacy of acalabrutinib and pembrolizumab in a limited group of B-cell malignancies. In the second stage, Part 2 allows for possible expansion cohorts into a wider range of B-cell malignancies, and Part 3 will evaluate the combination in subjects with myelofibrosis (MF).

Eligibility criteria: Main Inclusion Criteria:

* Diagnosis of a hematologic malignancy as documented by medical records and with histology based on criteria established by the World Health Organization (WHO).
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
* Agreement to use contraception during the study and for 90 days after the last dose of ACP-196 or 120 days after the last dose of pembrolizumab, if sexually active and able to bear or beget children.
* Completion of all therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥ 4 weeks before the start of study therapy.
* ANC ≥ 0.5 x 10\^9/L or platelet count ≥ 50 x 10\^9/L unless due to disease involvement in the bone marrow.

Main 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 study drugs, or put the study outcomes at undue risk.
* Central nervous system (CNS) involvement by lymphoma/leukemia
* Any therapeutic antibody within 4 weeks of first dose of study drugs.
* Total bilirubin \> 1.5 x ULN; and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3.0 x ULN.
* Estimated creatinine clearance of \< 30 mL/min, calculated using the formula of Cockcroft and Gault (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: 104 weeks
measure: Number of Participants With Grade 3-4 Adverse Events
timeFrame: 104 weeks
measure: Number of Participants With Grade 5 Adverse Events
timeFrame: 104 weeks
measure: Number of Participants With Any Study-Drug Related AE
timeFrame: 104 weeks
measure: Number of Participants With Grade 3-4 Study-Drug Related AE
timeFrame: 104 weeks
measure: Number of Participants With Grade 5 Study-Drug Related AE
timeFrame: 104 weeks
measure: Number of Participants With Any SAE
timeFrame: 104 weeks
measure: Number of Participants With Grade 3-4 Any SAE
timeFrame: 104 weeks
measure: Number of Participants With Grade 5 Any SAE
timeFrame: 104 weeks
measure: Number of Participants With Any Study Drug-Related SAE
timeFrame: 104 weeks
measure: Number of Participants With Any Grade 3-4 Study Drug-Related SAE
timeFrame: 104 weeks
measure: Number of Participants With Any Grade 5 Study Drug-Related SAE
timeFrame: 104 weeks
measure: Number of Participants With AE Leading to Study Drug Discontinuation, Modification or Delay
timeFrame: 104 weeks
measure: Number of Participants With AE Leading to Study Drug Discontinuation
timeFrame: 104 weeks
measure: Number of Participants With AE Leading to Study Drug Delay
timeFrame: 104 weeks
measure: Number of Participants With AE Leading to Study Drug Modification
timeFrame: 104 weeks
Secondary outcomes:
measure: Overall Response Rate
timeFrame: 104 weeks
measure: Duration of Response
timeFrame: 104 weeks
measure: Progression-free Survival
timeFrame: 104 weeks
measure: Overall Survival
timeFrame: 104 weeks
measure: Time to Next Treatment
timeFrame: 104 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Niles
country: United States
facility: Research Site
state: Illinois
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Tyler
country: United States
facility: Research Site
state: Texas
city: Fairfax
country: United States
facility: Research Site
state: Virginia
city: Roanoke
country: United States
facility: Research Site
state: Virginia
city: Vancouver
country: United States
facility: Research Site
state: Washington
city: Yakima
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: 1-877-240-9479 - information.center@astrazeneca.com
name: AstraZeneca Clinical Study Information Center
role: STUDY_DIRECTOR
References: