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

NCT ID: NCT03205046

Last Updated: 2021-01-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-29
• Study Completion Date: 2019-11-20

Brief Summary

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

Conditions

DLBCL; Richter Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1 continuous dose for vistusertib

acalabrutinib daily + vistusertib daily

Group Type: EXPERIMENTAL

acalabrutinib

Intervention Type: DRUG

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

vistusertib

Intervention Type: DRUG

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

Part 1 intermittent dose for vistusertib

acalabrutinib daily + vistusertib 5 days on and 2 days off

Group Type: EXPERIMENTAL

acalabrutinib

Intervention Type: DRUG

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

vistusertib

Intervention Type: DRUG

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

Interventions

acalabrutinib

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

Intervention Type: DRUG

vistusertib

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

Intervention Type: DRUG

Other Intervention Names

ACP-196; AZD2014

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Acerta Pharma BV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Acerta Clinical Trials

Role: STUDY_DIRECTOR

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

Locations

Research Site

Fairway, Kansas, United States

Research Site

Bethesda, Maryland, United States

Research Site

Rochester, Minnesota, United States

Research Site

Omaha, Nebraska, United States

Research Site

Hackensack, New Jersey, United States

Research Site

Nashville, Tennessee, United States

Research Site

Seattle, Washington, United States

Research Site

Headington, , United Kingdom

Research Site

London, , United Kingdom

Research Site

Nottingham, , United Kingdom

Research Site

Sutton, , United Kingdom

Countries

United States; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34269152 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Related Info

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Related Info

Other Identifiers

ACE-LY-110

Identifier Type: -

Identifier Source: org_study_id