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Lymphomas Non-Hodgkin's B-CellEarly Phase 1AvR-CHOPNCT03244176

Feasibility Study of Induction and Maintenance Avelumab Plus R-CHOP in Patients With Diffuse DLBCL: The AvR-CHOP Study

A Early Phase 1 study testing Avelumab in people with Lymphomas Non-Hodgkin's B-Cell, run by Austin Health at 3 sites in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

To evaluate the feasibility of adding induction and maintenance Avelumab to the standard combination of R-CHOP in patients with stage II, III and IV diffuse large B cell lymphoma (DLBCL) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphomas Non-Hodgkin's B-Cell
What is being tested?
Avelumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
3 sitesAustralia
Study dates
21 Jul 2017to Jul 2025
Phase
Early 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

  • Male or Female subjects aged 18 years.
  • Histologically proven CD20-positive diffuse large B cell non-Hodgkin lymphoma (DLBCL) according to the current World Health Organization classification including all morphological variants.
  • No previous treatment for lymphoma including chemotherapy, radiotherapy or other investigational drug.
  • Stage II, III and IV disease (Ann Arbor criteria) (must be able to undergo PET/CT imaging for staging purposes.)
  • Eastern Collaborative Oncology Group performance status 0, or 1, unless attributable to lymphoma in which case patients of performance status 2 are also eligible.
  • Adequate bone marrow function with platelets > 100x109/l; neutrophils > 1.5x109/l at the time of study entry unless attributed to bone marrow infiltration by lymphoma.
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  • Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
  • Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × upper limit of institutional normal range unless attributed to lymphoma.
  • Patients must have an acceptable left ventricular ejection fraction (LVEF) i.e. within the local normal range for multigated acquisition scan (MUGA) or ≥ 45% on echocardiogram
  • No concurrent uncontrolled medical condition as determined by the investigator.
  • Life expectancy > 3 months.
  • Negative blood pregnancy test at screening for women of childbearing potential. Effective contraception for both male and female subjects if the risk of conception exists.
  • Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management.

Who cannot join

  • T-cell lymphoma, transformed follicular lymphoma, grade 3B Follicular lymphoma.
  • Previous history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed with an indolent lymphoma, who have diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included after consultation with the sponsor.
  • Central nervous system, meningeal or spinal cord involvement by lymphoma.
  • Prior therapy with any antibody or drug targeting T-cell coregulatory proteins (immune checkpoints) such as PD-1, PD-L1, or cytotoxic T-lymphocyte antigen-4 (CTLA-4).
  • Patients with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
  • Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible ii) Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day iii) Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable.
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  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 15 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 15 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma) h) Past history of interstitial lung disease. i) Prior organ transplantation, including allogeneic stem-cell transplantation j) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
  • Neurological contra-indication to vincristine (e.g. pre-existing diabetic neuropathy >grade 1) l) Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the subject has not fully recovered from the surgery within 4 weeks of enrolment m) Any other serious active disease, including but not limited to; i) pregnancy or lactation, ii) clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina pectoris, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious cardiac arrhythmia requiring medication (including QTc prolongation of > 470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome.
  • or, uncontrolled active infection, iv) or, uncontrolled diabetes (e.g., hemoglobin A1c ≥ 8%) n) Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS), Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive) o) Medical or psychiatric conditions that compromise the patient's ability to give informed consent.

Trial locations and contacts

3 sites in 1 country.

Australia3 sites

  • Ballarat Health

    Ballarat, Victoria, 3350

  • Eastern Health

    Box Hill, Victoria, 3128

  • Austin Health

    Heidelberg, Victoria, 3084

Other trials in Australia

About this study

Official title: Feasibility Study of Induction and Maintenance Avelumab Plus R-CHOP in Patients With Diffuse Large B Cell Lymphoma (DLBCL): The AvR-CHOP Study

To evaluate the feasibility of adding induction and maintenance Avelumab to the standard combination of R-CHOP in patients with stage II, III and IV diffuse large B cell lymphoma (DLBCL)

Read the detailed description

The rationale and primary objective is to evaluate the feasibility of adding induction and maintenance Avelumab into the standard Rituximab, Cyclophosphamide, Doxyrubicin, Vincristine and Prednisolone (RCHOP) regimen in order to examine the effect of programmed death-ligand 1(PDL1) inhibition in patients with stage II, III and IV DLBCL.

Primary endpoint:

  • Immune related toxicity which requires discontinuation of Avelumab.

Secondary endpoints:

  • Response rates (according to the Lugano classification for Response Criteria for NonHodgkin Lymphoma);
  • Failure free survival;
  • Overall survival;
  • Overall toxicity of treatment (according to CTCAE v 4.0).

Methodology:

All patients (n=28) will receive Avelumab and rituximab 2 weekly for 2 cycles, then RCHOP chemotherapy 3 weekly for 6 cycles then Avelumab 2 weekly for 6 cycles.

The sequential treatment schedule has been designed for several reasons: concurrent Avelumab and RCHOP might result in reduced efficacy of Avelumab owing to the high dose prednisolone component of RCHOP; immune related toxicities of Avelumab given concurrently with RCHOP might result in chemotherapy dose delays and reduced chemotherapy efficacy; the Avelumab plus rituximab prephase will allow for the preliminary assessment of nonchemotherapy agents Avelumab plus rituximab in treatment naïve patients.

Assessments:

  • Patients will be reviewed at baseline and prior to each cycle of treatment for toxicity
  • Positron emission tomography-computed tomography (PET/CT) will be performed at baseline, after induction phase, after cycle 2 RCHOP, at end of Avelumab (Av) RCHOP and at end of maintenance phase Avelumab.
  • Following completion of treatment, patients will be followed up for a total of 5 years (at 3,6,9,12,18,24,36,48 and 60 months posttreatment). No formal routine imaging will be performed during follow up. In patients with relapse, follow up only for survival will be every 3 months.
Being tested
Avelumab
Keywords
DLBCL
Medical subject headings
Lymphoma, B-Cell

What participants receive

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

  • AvelumabDrug

    Also called MSB0010718C

    All participants will receive the following treatment:

    Induction phase Avelumab at a dose of 10 mg/kg as a 1hour intravenous (IV) infusion once every 2 weeks for 2 cycles Plus Rituximab at a dose of 375mg/m2 as an IV infusion over at least 1 hour once every 2 weeks for 2 treatments

    Then:

    RCHOP - All participants will receive RCHOP chemotherapy treatment for 6 cycles. Each cycle will last for 21 days. Rituximab, cyclophosphamide, doxorubicin, and vincristine are given on the first day of each cycle by intravenous infusion. Prednisone is given orally from Day 1 until Day 5 of each cycle.

    Then:

    Maintenance phase - All participants will receive Avelumab at a dose of 10 mg/kg as a 1hour intravenous (IV) infusion once every 2 weeks for 6 cycles.

Study groups in NCT03244176
Study groupRoleWhat they receive
Open-labelOtherAvelumab - Single-arm open label study
Receives: Drug: Avelumab

What is being measured

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

  1. Immune-related toxicity

    Immune-related toxicity which requires discontinuation of Avelumab

    Measured: 12 months

Secondary outcomes (4)

  1. Response Rate

    Response Rate to Avelumab + RCHOP according to the Lugano classification for Response Criteria for Non-Hodgkin Lymphoma

    Measured: 2 years

  2. Failure Free Survival

    Duration of survival without additional systemic therapy, relapse or non-relapse mortality

    Measured: 2 years

  3. Overall Survival

    Duration of patient survival

    Measured: 2 years

  4. Overall Toxicity of Treatment

    Overall toxicity as assessed by CTCAE v4.0

    Measured: 12 months

Timeline

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

  1. First posted9 Aug 2017
  2. Study start21 Jul 2017
  3. Primary completion16 Jun 2022
  4. Study completionJul 2025 (estimated)

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
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03244176
Sponsor's protocol ID
MS100070-0068
Acronym
AvR-CHOP
Status last verified
Jul 2024
First submitted
7 Aug 2017
Last updated
30 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: IPD is the property of the Sponsor (Austin Health). Results from the research intends to be published/presented in relevant publications/conferences for colleague review

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Avelumab in people with Lymphomas Non-Hodgkin's B-Cell, run by Austin Health at 3 sites in Australia.

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 13 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 30 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 3 sites in Australia. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

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

Are results available for this 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?

Immune-related toxicity (time frame: 12 months). 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 NCT03244176.

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 30 Jul 2024.

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