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

NCT03205046 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: ACE-LY-110
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 11

Brief Summary

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

Conditions

DLBCL; Richter Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (AEs)

  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).

  From first dose of study drug until 30 days post last dose

Study Arms (2)

Part 1 continuous dose for vistusertib

EXPERIMENTAL

acalabrutinib daily + vistusertib daily

Drug: acalabrutinib; Drug: vistusertib

Part 1 intermittent dose for vistusertib

EXPERIMENTAL

acalabrutinib daily + vistusertib 5 days on and 2 days off

Drug: acalabrutinib; Drug: vistusertib

Interventions

acalabrutinib DRUG

Acalabrutinib is a selective, irreversible small molecule Bruton's tyrosine kinase (BTK) inhibitor.

Also known as: ACP-196

Part 1 continuous dose for vistusertib; Part 1 intermittent dose for vistusertib

vistusertib DRUG

Vistusertib is an inhibitor of mechanistic target of rapamycin (mTOR) kinase

Also known as: AZD2014

Part 1 continuous dose for vistusertib; Part 1 intermittent dose for vistusertib

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Men and women ≥18 years of age.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• 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).

You may not qualify if:

• 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.
• Diagnosis of PMBCL.
• 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.
• History of central nervous system (CNS) lymphoma, leptomeningeal disease or spinal cord compression.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Acerta Pharma BV: lead

Study Sites (11)

Research Site

Fairway, Kansas, 66205, United States

Location

Research Site

Bethesda, Maryland, 20892, United States

Location

Research Site

Rochester, Minnesota, 55902, United States

Location

Research Site

Omaha, Nebraska, 68198, United States

Location

Research Site

Hackensack, New Jersey, 07601, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Seattle, Washington, 98109, United States

Location

Research Site

Headington, OX3 7LJ, United Kingdom

Location

Research Site

London, EC1A 7BE, United Kingdom

Location

Research Site

Nottingham, NG5 1PB, United Kingdom

Location

Research Site

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Collins GP, Clevenger TN, Burke KA, Yang B, MacDonald A, Cunningham D, Fox CP, Goy A, Gribben J, Nowakowski GS, Roschewski M, Vose JM, Vallurupalli A, Cheung J, Raymond A, Nuttall B, Stetson D, Dougherty BA, Schalkwijk S, Carnevalli LS, Willis B, Tao L, Harrington EA, Hamdy A, Izumi R, Pease JE, Frigault MM, Flinn I. A phase 1/2 study of the combination of acalabrutinib and vistusertib in patients with relapsed/refractory B-cell malignancies. Leuk Lymphoma. 2021 Nov;62(11):2625-2636. doi: 10.1080/10428194.2021.1938027. Epub 2021 Jul 16.

  PMID: 34269152 DERIVED

Related Links

• Related Info
• Related Info

MeSH Terms

Interventions

acalabrutinib; vistusertib

Limitations and Caveats

Enrollment to this study was stopped early by the sponsor and an abbreviated CSR was generated.

Results Point of Contact

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

acertamc@dlss.com

1-888-292-9613

Study Officials

• Acerta Clinical Trials

  1-888-292-9613; acertamc@dlss.com

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2017
• First Posted: July 2, 2017
• Study Start: June 29, 2017
• Primary Completion: November 20, 2019
• Study Completion: November 20, 2019
• Last Updated: January 6, 2021
• Results First Posted: January 6, 2021

Record last verified: 2020-12

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 (7); GB (4)