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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03244176




Registration number
NCT03244176
Ethics application status
Date submitted
7/08/2017
Date registered
9/08/2017
Date last updated
1/02/2023

Titles & IDs
Public title
Feasibility Study of Induction and Maintenance Avelumab Plus R-CHOP in Patients With Diffuse DLBCL: The AvR-CHOP Study
Scientific title
Feasibility Study of Induction and Maintenance Avelumab Plus R-CHOP in Patients With Diffuse Large B Cell Lymphoma (DLBCL): The AvR-CHOP Study
Secondary ID [1] 0 0
MS100070-0068
Universal Trial Number (UTN)
Trial acronym
AvR-CHOP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphomas Non-Hodgkin's B-Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab

Other: Open-label - Avelumab - Single-arm open label study


Treatment: Drugs: Avelumab
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Immune-related toxicity
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Response Rate
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Failure Free Survival
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Overall Toxicity of Treatment
Timepoint [4] 0 0
12 months

Eligibility
Key inclusion criteria
1. Male or Female subjects aged 18 years.

2. Histologically proven CD20-positive diffuse large B cell non-Hodgkin lymphoma (DLBCL)
according to the current World Health Organization classification including all
morphological variants.

3. No previous treatment for lymphoma including chemotherapy, radiotherapy or other
investigational drug.

4. Stage II, III and IV disease (Ann Arbor criteria) (must be able to undergo PET/CT
imaging for staging purposes.)

5. Eastern Collaborative Oncology Group performance status 0, or 1, unless attributable
to lymphoma in which case patients of performance status 2 are also eligible.

6. 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.

7. Adequate renal function defined by an estimated creatinine clearance = 30 mL/min
according to the Cockcroft-Gault formula (or local institutional standard method)

8. 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.

9. 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

10. No concurrent uncontrolled medical condition as determined by the investigator.

11. Life expectancy > 3 months.

12. 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.

13. Signed written informed consent before any trial-related procedure is undertaken that
is not part of the standard patient management.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. T-cell lymphoma, transformed follicular lymphoma, grade 3B Follicular lymphoma.

2. 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.

3. Central nervous system, meningeal or spinal cord involvement by lymphoma.

4. 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).

5. Patients with active autoimmune disease that might deteriorate when receiving an
immunostimulatory agent:

i) 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.

f) 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.

g) 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.

k) 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.

iii) 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 0
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/07/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2025
Actual
Sample size
Target
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Ballarat Health - Ballarat
Recruitment hospital [2] 0 0
Eastern Health - Box Hill
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
3350 - Ballarat
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
Austin Health
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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)
Trial website
https://clinicaltrials.gov/ct2/show/NCT03244176
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eliza Hawkes, MD
Address 0 0
Austin Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03244176