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Lymphoma, Large B-Cell, DiffusePhase 1NCT04790903

A Study Evaluating the Safety, Efficacy and Pharmacokinetics of Venetoclax in Combination With Polatuzumab Vedotin Plus Rituximab (R) and Cyclophosphamide, Doxorubicin, Prednisone (CHP) in Participants With Untreated BCL-2 Immunohistochemistry (IHC)-Positive Diffuse Large B-Cell Lymphoma (DLBCL)

A Phase 1 study testing Venetoclax, Polatuzumab Vedotin and Rituximab in people with Lymphoma, Large B-Cell, Diffuse, run by Hoffmann-La Roche at 20 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This Phase Ib, open-label, multicenter study evaluates the safety, efficacy, and pharmacokinetics of venetoclax in combination with Pola + R-CHP in previously untreated participants with BCL-2 IHC-positive DLBCL. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Large B-Cell, Diffuse
What is being tested?
Venetoclax, Polatuzumab Vedotin and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
20 sitesin 4 countries
Study dates
2 Jul 2021to 21 May 2024
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Previously untreated participants with CD20-positive DLBCL.
  • BCL-2 protein overexpression by IHC, as assessed by local testing.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
  • International Prognostic Index (IPI) 2-5.
  • Life expectancy of more than 6 months.
  • Left ventricular ejection fraction (LVEF) ≥ 50%, as determined on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO).
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  • Availability of archival or freshly collected tumor tissue prior to study enrollment.
  • At least one bi-dimensionally fluorodeoxyglucose-avid measurable lymphoma lesion on PET/CT scan, defined as > 1.5 cm in its longest dimension on CT scan.
  • Adequate hematopoietic function.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.

Who cannot join

  • Current diagnosis of unclassifiable B-cell lymphoma.
  • Prior treatment for indolent lymphoma.
  • Current Grade > 1 peripheral neuropathy.
  • Prior organ transplantation.
  • Prior use of any monoclonal antibody within 3 months and any investigational therapy within 28 days prior to the start of Cycle 1.
  • Vaccination with live vaccines within 28 days prior to the start of Cycle 1.
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  • Prior therapy for DLBCL and High-Grade B-cell Lymphoma (HGBCL) with the exception of palliative, short-term treatment with corticosteroids.
  • Recent major surgery (within 6 weeks prior to the start of Day 1 of Cycle 1), other than for diagnosis.
  • History of other cancers within 2 years prior to screening.
  • Any active infection that, in the opinion of the investigator, would impact participant safety within 7 days prior to Day 1 of Cycle 1.
  • Serious infection requiring oral or IV antibiotics within 4 weeks prior to Day 1 of Cycle 1.
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study.
  • Positive test for Hepatitis B/C Viruses (HBV/HCV) and Human T-cell Leukemia Virus (HTLV)-1.
  • Known infection with HIV.
  • History of progressive multifocal leukoencephalopathy.
  • Suspected active or latent tuberculosis.
  • Clinically significant history of liver disease, including viral or other hepatitis or cirrhosis.
  • Substance abuse, including non-prescription drug and alcohol dependence, within 12 months prior to screening.
  • Pregnant or breastfeeding, or intending to become pregnant during the study within 6 months after the final dose of venetoclax, 9 months after the final dose of polatuzumab vedotin, or 12 months after the final dose of rituximab.
  • History or presence of an abnormal ECG that is clinically significant in the investigator's opinion.
  • Malabsorption syndrome or other condition that would interfere with enteral absorption.
  • Blood transfusion within 14 days prior to screening.

Trial locations and contacts

20 sites in 4 countries.

20 sites in 4 countries

France7 sites

  • Centre Hospitalier Régional Universitaire de Lille (CHRU) - Hôpital Claude Huriez

    Lille, 59037

  • CHU Montpellier - Saint ELOI

    Montpellier, 34295

  • CHU de Nantes; Cancéro-dermatologie

    Nantes, 44093

  • Hôpital Saint-Louis

    Paris, 75475

  • Centre Hospitalier Lyon Sud; Service d'Oncologie Médicale

    Pierre-Bénite, 69310

  • CHU Rennes - Hopital Pontchaillou

    Rennes, 35033

  • Centre Henri Becquerel

    Rouen, 76038

Other trials in France

Italy5 sites

  • Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; Dip. Scienze Mediche e Chirurgiche

    Bologna, Emilia-Romagna, 40138

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST; Farmacia Oncologica

    Meldola, Emilia-Romagna, 47014

  • Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica

    Naples, Campania, 80131

  • Azienda Ospedaliero Universitaria Pisana-Ospedale Santa Chia

    Pisa, Piedmont, 56126

  • Ospedale Santa Maria Delle Croci

    Ravenna, Emilia-Romagna, 48100

Other trials in Italy

Spain5 sites

  • Hospital de la Santa Creu i Sant Pau; Servicio de Dermatologia

    Barcelona, 08025

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital General Univ. Gregorio Maranon

    Madrid, 28007

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario La Fe; Servicio de Farmacia

    Valencia, 46026

Other trials in Spain

United States3 sites

  • SARAH CANNON RESEARCH INST.; Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203

  • NYU Langone Hospitals, NYU Langone Rusk Ambulatory Surgical Pharmacy

    New York, New York, 10016

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase Ib Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Venetoclax in Combination With Polatuzumab Vedotin Plus Rituximab (R) and Cyclophosphamide, Doxorubicin, Prednisone (CHP) in Patients With Untreated BCL-2 Immunohistochemistry (IHC)-Positive Diffuse Large B-Cell Lymphoma

This Phase Ib, open-label, multicenter study evaluates the safety, efficacy, and pharmacokinetics of venetoclax in combination with Pola + R-CHP in previously untreated participants with BCL-2 IHC-positive DLBCL. Approximately 50 participants will be enrolled in this study in five consecutive cohorts each consisting of approximately 10 participants.

Being tested
Venetoclax, Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VenetoclaxDrug

    Participants will self-administer Venetoclax, as described in the Arm Descriptions.

  • Polatuzumab VedotinDrug

    Participants will receive Polatuzumab Vedotin at a dose of 1.8 mg/kg by intravenous (IV) infusion on Day 1 of Cycles 1-6.

  • RituximabDrug

    Participants will receive Rituximab at a dose of 375 mg/m^2 by IV infusion on Day 1 of Cycles 1-6.

  • CyclophosphamideDrug

    Participants will receive Cyclophosphamide at a dose of 750 mg/m^2 by IV infusion or bolus on Day 1 of Cycles 1-6.

  • DoxorubicinDrug

    Participants will receive Doxorubicin at a dose of 50 mg/m^2 by IV infusion or bolus on Day 1 of Cycles 1-6.

  • PrednisoneDrug

    Participants will receive Prednisone orally (PO) at a dose of 100 mg/day on Days 1-5 of Cycles 1-6.

Study groups in NCT04790903
Study groupRoleWhat they receive
Venetoclax (Schedule A)ExperimentalParticipants enrolled in dosing Schedule A will receive a total of six 21-day cycles of venetoclax treatment for 5 days in combination with Polatuzumab Vedotin + R-CHP (Rituximab, Cyclophosphamide, Doxorubicin and Prednisone) as described below: Schedule A: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 5 consecutive days as follows: Cycle 1: 5 consecutive days of dosing on Days 4-8. Cycles 2-6: 5 consecutive days of dosing on Days 1-5.
Receives: Drug: Venetoclax; Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone
Venetoclax (Schedule B)ExperimentalParticipants enrolled in dosing Schedule B will receive a total of six 21-day cycles of venetoclax treatment for 10 days in combination with Polatuzumab Vedotin + R-CHP as described below: Schedule B: Participants will self-administer Venetoclax orally (PO) once daily (QD) at a dose of 800 mg for 10 consecutive days as follows: Cycle 1: 10 consecutive days of dosing on Days 4-10. Cycles 2-6: 10 consecutive days of dosing on Days 1-10.
Receives: Drug: Venetoclax; Drug: Polatuzumab Vedotin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with Dose-Limiting Toxicities (DLTs)

    Measured: Cycle 1 Day 1 up to but not including Cycle 3 Day 1 (Cycle length = 21 days)

Secondary outcomes (7)

  1. Percentage of Participants with Adverse Events (AEs)

    Measured: Up to 4 years

  2. Complete Response (CR) rate at the end of treatment

    Assessed by the investigator on PET and computed tomography (PET/CT) scans according to the Lugano Response Criteria for Malignant Lymphoma (Cheson et al. 2014)

    Measured: Up to 4 years

  3. Objective Response Rate (ORR) at the end of treatment

    Defined as the proportion of patients with a CR or a partial response (PR), as determined by the investigator on PET/CT scans according to the Lugano 2014 Response Criteria

    Measured: Up to 4 years

  4. Duration of Response (DOR)

    Defined as the time from the first occurrence of a documented objective response (a PR or a CR) to disease progression, relapse, or death from any cause (whichever occurs first), as determined by the investigator according to the Lugano 2014 Response Criteria

    Measured: Up to 4 years

  5. Progression-Free Survival (PFS)

    Defined as the time from the date of first study treatment to the first occurrence of disease progression or relapse, as assessed by the investigator, according to the Lugano 2014 Response Criteria, or death from any cause, whichever occurs earlier

    Measured: Up to 4 years

  6. Plasma Concentrations of Venetoclax at specified timepoints

    Measured: Up to 4 years

  7. Plasma Concentrations of Polatuzumab Vedotin analytes at specified timepoints

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2021
  2. Study start2 Jul 2021
  3. Primary completion21 May 2024
  4. Study completion21 May 2024

Why it stopped: Decision to discontinue the study based on broader development and strategic prioritisation. The Sponsor concludes there is no benefit-risk impact on the BO42203 study.

Resources

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04790903
Sponsor's protocol ID
BO42203
Other IDs
2020-002376-12
Status last verified
Jul 2024
First submitted
8 Mar 2021
Last updated
11 Jul 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax, Polatuzumab Vedotin and Rituximab in people with Lymphoma, Large B-Cell, Diffuse, run by Hoffmann-La Roche at 20 sites in 4 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 11 inclusion and 22 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 11 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in France, Italy, Spain, United States. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Decision to discontinue the study based on broader development and strategic prioritisation. The Sponsor concludes there is no benefit-risk impact on the BO42203 study.). Results are not available in the source record.

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?

Percentage of Participants with Dose-Limiting Toxicities (DLTs) (time frame: Cycle 1 Day 1 up to but not including Cycle 3 Day 1 (Cycle length = 21 days)). 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 NCT04790903.

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 11 Jul 2024.

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