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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03205046
Recruitment Status : Terminated (Sponsor's decision not to pursue further development of the combination in DLBCL)
First Posted : July 2, 2017
Results First Posted : January 6, 2021
Last Update Posted : January 6, 2021
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

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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 : June 29, 2017
Actual Primary Completion Date : November 20, 2019
Actual Study Completion Date : November 20, 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. Number of Participants With Treatment-Emergent Adverse Events (AEs) [ Time Frame: From first dose of study drug until 30 days post last dose ]
    Safety assessments comprised type, frequency, severity, and relationship to either or both study drug of any AEs or abnormalities of laboratory tests; serious adverse events (SAEs); dose-limiting toxicities (DLTs); or AEs that led to dose modification, dose delay, or discontinuation of study drug(s).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (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
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United States, Kansas
Research Site
Fairway, Kansas, United States, 66205
United States, Maryland
Research Site
Bethesda, Maryland, United States, 20892
United States, Minnesota
Research Site
Rochester, Minnesota, United States, 55902
United States, Nebraska
Research Site
Omaha, Nebraska, United States, 68198
United States, New Jersey
Research Site
Hackensack, New Jersey, United States, 07601
United States, Tennessee
Research Site
Nashville, Tennessee, United States, 37203
United States, Washington
Research Site
Seattle, Washington, United States, 98109
United Kingdom
Research Site
Headington, United Kingdom, OX3 7LJ
Research Site
London, United Kingdom, EC1A 7BE
Research Site
Nottingham, United Kingdom, NG5 1PB
Research Site
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Acerta Pharma BV
Investigators
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Study Director: Acerta Clinical Trials 1-888-292-9613; acertamc@dlss.com
  Study Documents (Full-Text)

Documents provided by Acerta Pharma BV:
Study Protocol  [PDF] March 29, 2019
Statistical Analysis Plan  [PDF] August 16, 2018

Additional Information:
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Responsible Party: Acerta Pharma BV
ClinicalTrials.gov Identifier: NCT03205046    
Other Study ID Numbers: ACE-LY-110
First Posted: July 2, 2017    Key Record Dates
Results First Posted: January 6, 2021
Last Update Posted: January 6, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Statistical Analysis Plan (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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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