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A Study of Acalabrutinib and Vistusertib in Subjects With Relapsed/Refractory B-cell Malignancies

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ClinicalTrials.gov Identifier: NCT03205046
Recruitment Status : Active, not recruiting
First Posted : July 2, 2017
Last Update Posted : June 4, 2018
Sponsor:
Information provided by (Responsible Party):
Acerta Pharma BV

Brief Summary:
This study evaluates the safety of acalabrutinib and vistusertib when taken in combination.

Condition or disease Intervention/treatment Phase
DLBCL Richter Syndrome Drug: acalabrutinib Drug: vistusertib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Proof-of-Concept Study of the Combination of Acalabrutinib and Vistusertib in Subjects With Relapsed/Refractory B-cell Malignancies
Actual Study Start Date : July 11, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 continuous dose for vistusertib
acalabrutinib daily + vistusertib daily
Drug: acalabrutinib
Acalabrutinib is a selective, irreversible small molecule Bruton's tyrosine kinase (BTK) inhibitor.
Other Name: ACP-196

Drug: vistusertib
Vistusertib is an inhibitor of mechanistic target of rapamycin (mTOR) kinase
Other Name: AZD2014

Experimental: Part 1 intermittent dose for vistusertib
acalabrutinib daily + vistusertib 5 days on and 2 days off
Drug: acalabrutinib
Acalabrutinib is a selective, irreversible small molecule Bruton's tyrosine kinase (BTK) inhibitor.
Other Name: ACP-196

Drug: vistusertib
Vistusertib is an inhibitor of mechanistic target of rapamycin (mTOR) kinase
Other Name: AZD2014




Primary Outcome Measures :
  1. Part 1: Identify a dose and schedule for vistusertib for Part 2 as determined by the number of participants at each dose level with dose limiting toxicities. [ Time Frame: 28 days ]
    Number of participants experiencing dose-limiting toxicities

  2. Part 2: Evaluation of the safety of acalabrutinib and vistusertib when coadministered [ Time Frame: 12 months ]
    Incidence of adverse events from the combination of acalabrutinib and vistusertib


Secondary Outcome Measures :
  1. To evaluate the pharmacokinetics (PK) of acalabrutinib and vistusertib when coadministered [ Time Frame: 12 months ]
    To evaluate the pharmacokinetics (PK) of acalabrutinib and vistusertib when coadministered, as measured by an Area under the plasma concentration versus time curve (AUC).

  2. To evaluate the pharmacokinetics (PK) of acalabrutinib and vistusertib when coadministered [ Time Frame: 12 months ]
    To evaluate the pharmacokinetics (PK) of acalabrutinib and vistusertib when coadministered, as measured by Peak Plasma Concentration (Cmax).

  3. To evaluate the clinical activity of acalabrutinib and vistusertib when coadministered [ Time Frame: 12 months ]
    To evaluate the clinical activity of acalabrutinib and vistusertib when coadministered, as measured by overall response rate (ORR).

  4. To evaluate the clinical activity of acalabrutinib and vistusertib when coadministered [ Time Frame: 12 months ]
    To evaluate the clinical activity of acalabrutinib and vistusertib when coadministered, as measured by duration of response (DOR).

  5. To evaluate the clinical activity of acalabrutinib and vistusertib when coadministered [ Time Frame: 12 months ]
    To evaluate the clinical activity of acalabrutinib and vistusertib when coadministered, as measured by durable response rate (DRR).

  6. To evaluate the clinical activity of acalabrutinib and vistusertib when coadministered [ Time Frame: 12 months ]
    To evaluate the clinical activity of acalabrutinib and vistusertib when coadministered, as measured by progression-free survival (PFS).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) as documented by medical records and with histology based on criteria established by The World Health Organization (WHO):

    • If a subject has de novo DLBCL, the diagnosis is confirmed by biopsy and is immunohistologically characterized as de novo germinal center B-cell-like (GCB) DLBCL or de novo non-GCB DLBCL.
    • If the subjects has Richter's Syndrome (RS), the diagnosis is confirmed by biopsy and is immunohistologically characterized as transformation to DLBCL.
    • If the subjects has transformed DLBCL, the diagnosis is confirmed by biopsy and is immunohistologically characterized as transformation to DLBCL from indolent lymphoma (eg, follicular lymphoma).
  2. Men and women ≥18 years of age.
  3. Prior treatment for lymphoid malignancy:

    • If the subject has DLBCL, there is no curative option with conventional therapy and the prior treatment included ≥ 1 prior combination chemoimmunotherapy regimen.
    • If the subject has RS, the subject must have had ≥1 prior treatment with a combination chemoimmunotherapy regimen.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
  5. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of a ≥1.5 cm lesion, as measured in the longest dimension by computed tomography [CT] scan).

Exclusion Criteria:

  1. As judged by the Investigator, any evidence of severe or uncontrolled systemic disease (eg, severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension, history of, or active, bleeding diatheses (eg, hemophilia or von Willebrand disease) or uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks before first dose of study drug.
  2. Diagnosis of PMBCL.
  3. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
  4. History of central nervous system (CNS) lymphoma, leptomeningeal disease or spinal cord compression.
  5. Any clinically significant pre-existing severe renal disease (eg, glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis) or high risk of developing severe renal impairment.
  6. Abnormal echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) at baseline (left ventricular ejection fraction [LVEF] <40% and shortening fraction <15%). Appropriate correction to be used, if a MUGA is performed.
  7. Mean resting corrected QT interval (QTc) calculated using Fridericia's formula (QTcF) >450 msec obtained from 3 electrocardiograms (ECGs); family or personal history of long or short QT syndrome; Brugada syndrome or known history of QTc prolongation or torsade de pointes within 12 months of the subject entering the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03205046


Locations
United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
United States, Kansas
University of Kansas Cancer Center
Westwood, Kansas, United States, 66205
United States, Maryland
National Institutes of Health
Bethesda, Maryland, United States, 20892
United States, Minnesota
The Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Nebraska
The University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
John Theurer Cancer Center
Hackensack, New Jersey, United States, 07601
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Texas Oncology
Tyler, Texas, United States, 75702
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Swedish Health Services
Seattle, Washington, United States, 98122
United Kingdom
Barts Health NHS Trust
London, United Kingdom, E1 1BB
The Christine NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom, NG5 1PB
Oxford University Hospitals NHS Trust
Oxford, United Kingdom, 0X3 7LE
Derriford Hospital
Plymouth, United Kingdom, PL4 7QD
The Royal Marsden
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Acerta Pharma BV
Investigators
Study Director: Ahmed Hamdy, MD Acerta Pharma BV

Responsible Party: Acerta Pharma BV
ClinicalTrials.gov Identifier: NCT03205046     History of Changes
Other Study ID Numbers: ACE-LY-110
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: June 4, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No