DLBCLPhase 1/2NCT03205046
A Study of Acalabrutinib and Vistusertib in Subjects With Relapsed/Refractory B-cell Malignancies
A Phase 1/2 study testing acalabrutinib and vistusertib in people with DLBCL and Richter Syndrome, run by Acerta Pharma BV at 11 sites in 2 countries.
Trial summary
This study evaluates the safety of acalabrutinib and vistusertib when taken in combination. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- DLBCL, Richter Syndrome
- What is being tested?
- acalabrutinib and vistusertib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 29 Jun 2017to 20 Nov 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 10Show fewer
- 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).
Who cannot join
- 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.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States7 sites
Research Site
Bethesda, Maryland, 20892
Research Site
Fairway, Kansas, 66205
Research Site
Hackensack, New Jersey, 07601
Research Site
Nashville, Tennessee, 37203
Research Site
Omaha, Nebraska, 68198
Research Site
Rochester, Minnesota, 55902
Research Site
Seattle, Washington, 98109
United Kingdom4 sites
Research Site
Headington, OX3 7LJ
Research Site
London, EC1A 7BE
Research Site
Nottingham, NG5 1PB
Research Site
Sutton, SM2 5PT
About this study
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
This study evaluates the safety of acalabrutinib and vistusertib when taken in combination.
- Conditions
- DLBCL, Richter Syndrome
- Being tested
- acalabrutinib, vistusertib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
acalabrutinibDrug
Also called ACP-196
Acalabrutinib is a selective, irreversible small molecule Bruton's tyrosine kinase (BTK) inhibitor.
vistusertibDrug
Also called AZD2014
Vistusertib is an inhibitor of mechanistic target of rapamycin (mTOR) kinase
| Study group | Role | What they receive |
|---|---|---|
| Part 1 continuous dose for vistusertib | Experimental | acalabrutinib daily + vistusertib daily Receives: Drug: acalabrutinib; Drug: vistusertib |
| Part 1 intermittent dose for vistusertib | Experimental | acalabrutinib daily + vistusertib 5 days on and 2 days off Receives: Drug: acalabrutinib; Drug: vistusertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From first dose of study drug until 30 days post last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start29 Jun 2017
- Primary completion20 Nov 2019
- Study completion20 Nov 2019
Why it stopped: Sponsor's decision not to pursue further development of the combination in DLBCL
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DLBCLStudies of the same condition, open and under way.
- More trials run by Acerta Pharma BVThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acerta Pharma BV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Acerta Clinical Trials, Study director, 1-888-292-9613; acertamc@dlss.com
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03205046
- Sponsor's protocol ID
- ACE-LY-110
- Status last verified
- Dec 2020
- First submitted
- 27 Jun 2017
- Last updated
- 6 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 34269152
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03205046
- Acronym / sponsor ID
- ACE-LY-110
- Conditions
- DLBCL, Richter Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision not to pursue further development of the combination in DLBCL
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Acerta Pharma BVIndustry (pharma, biotech, devices)
- Study start
- 29 Jun 2017 (actual)
- Primary completion
- 20 Nov 2019 (actual)
- Study completion
- 20 Nov 2019 (actual)
- First posted
- 2 Jul 2017 (actual)
- Results
- Posted 6 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the safety of acalabrutinib and vistusertib when taken in combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 continuous dose for vistusertib | Experimental | Drug: acalabrutinib, Drug: vistusertibacalabrutinib daily + vistusertib daily |
| Part 1 intermittent dose for vistusertib | Experimental | Drug: acalabrutinib, Drug: vistusertibacalabrutinib daily + vistusertib 5 days on and 2 days off |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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):
- Men and women ≥18 years of age.
- Prior treatment for lymphoid malignancy:
- 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).
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| acalabrutinibAlso: ACP-196Acalabrutinib is a selective, irreversible small molecule Bruton's tyrosine kinase (BTK) inhibitor. | Drug | Part 1 continuous dose for vistusertib, Part 1 intermittent dose for vistusertib |
| vistusertibAlso: AZD2014Vistusertib is an inhibitor of mechanistic target of rapamycin (mTOR) kinase | Drug | Part 1 continuous dose for vistusertib, Part 1 intermittent dose for vistusertib |
Primary outcome
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34269152Collins 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.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Acerta Clinical Trials study director
1-888-292-9613; acertamc@dlss.com
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing acalabrutinib and vistusertib in people with DLBCL and Richter Syndrome, run by Acerta Pharma BV at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (AEs) (time frame: From first dose of study drug until 30 days post last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03205046, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2021.