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

Brief Title

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

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

Brief Summary

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

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

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

Condition

DLBCL

Intervention

acalabrutinib

Study Arms / Comparison Groups

 Part 1 continuous dose for vistusertib

Description:  acalabrutinib daily + vistusertib daily

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

25

Start Date

June 29, 2017

Completion Date

November 20, 2019

Primary Completion Date

November 20, 2019

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.
      

Gender

All

Ages

18 Years - 130 Years

Accepts Healthy Volunteers

No

Contacts

Acerta Clinical Trials, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

NCT ID

NCT03205046

Organization ID

ACE-LY-110

Responsible Party

Sponsor

Study Sponsor

Acerta Pharma BV

Study Sponsor

Acerta Clinical Trials, Study Director, 1-888-292-9613; [email protected]

Verification Date

December 2020