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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/NCT05788081




Registration number
NCT05788081
Ethics application status
Date submitted
15/03/2023
Date registered
28/03/2023
Date last updated
18/10/2023

Titles & IDs
Public title
Treatment Of Newly-diagnosed Follicular Lymphoma With CELMoD BMS-986369, Rituximab +/- Nivolumab.
Scientific title
Treatment Of Newly-diagnosed Follicular Lymphoma With CELMoD BMS-986369, Rituximab +/- Nivolumab: An Umbrella Bayesian Optimal Phase II Study.
Secondary ID [1] 0 0
IM048-1036
Universal Trial Number (UTN)
Trial acronym
TOP-FLOR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Follicular Lymphoma Stage II 0 0
Follicular Lymphoma Stage III 0 0
Follicular Lymphoma Stage IV 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 - BMS-986369
Treatment: Drugs - Nivolumab 10 MG/ML
Treatment: Drugs - Rituximab

Experimental: Arm A- BMS-986369 + Rituximab - Rituximab 375mg/m2 IV infusion Q4W + BMS-986369 0.4mg po D1-D14 of each cycle for 8 cycles, followed by Rituximab 375mg/m2 IV infusion Q12W in participants with CR/PR at end of induction

Experimental: Arm B- Nivolumab + BMS-986369 + Rituximab - Nivolumab 480mg IV infusion Q4W, Rituximab 375mg/m2 IV infusion Q4W and BMS-986369 0.4mg po D1-D14 of each cycle for 8 cycles, followed by Rituximab 375mg/m2 IV infusion Q12W in participants with CR/PR at end of induction


Treatment: Drugs: BMS-986369
BMS-986369 is an orally administered Cereblon-modulating compound

Treatment: Drugs: Nivolumab 10 MG/ML
Nivolumab is a fully humanised IgG4 blocking monoclonal antibody against PD-1.

Treatment: Drugs: Rituximab
Rituximab is a chimeric anti-CD20 antibody containing human IgG lambda and kappa constant regions with murine variable regions
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of patients who achieve a complete metabolic response in the absence of prohibitive toxicity with induction rituximab, BMS-986369 with or without nivolumab comprising 8 cycles of therapy with each cycle delivered every 4 weeks.
Timepoint [1] 0 0
Consent to 8 weeks after last induction treatment (maximum 44 weeks)
Secondary outcome [1] 0 0
To assess overall toxicity
Timepoint [1] 0 0
Day 1 to 30 days after the end of maintenance phase (up to maximum 32 months)
Secondary outcome [2] 0 0
To assess time to treatment failure
Timepoint [2] 0 0
Day 1 end of follow up period (up to a maximum of 5 years)
Secondary outcome [3] 0 0
Progression free survival
Timepoint [3] 0 0
Day 1 end of follow up period (up to a maximum of 5 years)
Secondary outcome [4] 0 0
Overall survival
Timepoint [4] 0 0
From date of enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years

Eligibility
Key inclusion criteria
1. Age 18+ years.

2. Histologically proven CD20 positive Follicular non Hodgkin lymphoma (FL) grades 1-3A
(i.e. classical follicular lymphoma according to the current World Health Organization
classification).3

3. No previous chemotherapy, or other investigational drug for this indication apart from
focal radiotherapy.

4. Stage II-IV disease (Ann Arbor criteria).

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

6. Deemed to need treatment by treating investigator. Reasons for treatment can include,
but are not limited to:

a. Any nodal or extranodal tumour mass >7cm AND/OR multiple extranodal disease sites b.
Involvement of at least 3 sites each with diameter >3cm c. Symptomatic splenic enlargement
d. Organ involvement/compression e. Ascites or pleural effusion f. Lactate Dehydrogenase
(LDH) elevated g. Presence of systemic symptoms h. Disease progression in preceding 3
months i. Evidence of marrow infiltration with marrow compromise. (e.g., Hb, WCC or plt
count below lower limit of institutional normal range).

g) Adequate bone marrow function including:

1. Haemoglobin >8.0 g/dL

2. White cell count (WCC) =2000/µL

3. Neutrophils >1.5 x 109/L

4. Platelets >75 x 109/L at the time of study entry, unless attributed to bone marrow
infiltration by lymphoma.

h) Adequate renal function with serum creatinine =1.5 x ULN or creatinine clearance (CrCl)
= 60mL/min (using Cockcroft-Gault formula, 24hr urine collection or eGFR).

Female CrCl = (140 - age in years) x weight (kg) x 0.85 72 x serum creatinine (mg/dL)

Male CrCl = (140 - age in years) x weight (kg) x 1.00 72 x serum creatinine (mg/dL) i)
Adequate hepatic function with AST/ALT =3x ULN and total bilirubin =1.5 x ULN (except
subjects with Gilbert syndrome, who can have a total bilirubin =3 mg/dL or =51.3 µmol/L).

j) Adequate left ventricular ejection fraction of >45% as demonstrated on a Gated Cardiac
Blood Pool Scan or echocardiogram.

k) Life expectancy > 3 months. l) Patients of childbearing potential willing to adhere to
the following contraceptive precautions. Refer to the Celgene-BMS-986369/CC-99282 Pregnancy
Prevention Plan (Appendix 4) for additional guidance.

1. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
the start of study treatment.

2. Females must not be breastfeeding.

3. FCBP must use appropriate method(s) of contraception to avoid pregnancy for 23 weeks
(30 days plus five half-lives of nivolumab) and 28 days for BMS 986369 post-treatment
completion.

4. Men who are sexually active with FCBP must use any contraceptive method with a failure
rate of less than 1% per year. They must agree to adhere to contraception for a period
of 90 days from the last day BMS-986369 and refrain from donating sperm.

5. Azoospermic males and FCBP who are continuously not heterosexually active are exempt
from contraceptive requirements. However, they must still undergo pregnancy testing as
described in this section.

m) Written, informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Follicular large B-cell Lymphoma (Grade 3B) transformed follicular lymphoma, other
indolent lymphomas.

2. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4
antibody or any other antibody or drug specifically targeting T-cell co-stimulation or
checkpoint pathways.

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

4. Patients with active, known or suspected autoimmune disease. Patients with well
controlled type I diabetes mellitus, coeliac disease, residual hypothyroidism due to
autoimmune condition only requiring hormone replacement, vitiligo or psoriasis not
requiring systemic treatment, or other conditions not expected to recur in the absence
of an external trigger are permitted to enrol.

5. Subjects with a condition requiring systemic treatment with either corticosteroids
(>10mg daily prednisone equivalents) or other immunosuppressive medications within 14
days of study drug administration. Inhaled or topical steroids, and adrenal
replacement therapy are permitted in the absence of active autoimmune disease.

6. Past history of interstitial lung disease.

7. Prior organ transplantation or allogeneic bone marrow transplantation.

8. Prior malignancy active within the previous 2 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.

9. Uncontrolled or severe cardiovascular disease (NYHA class III or IV heart failure;
myocardial infarction within the last 6 months of study entry); unstable angina;
unstable cardiac arrhythmias; clinically significant pericardial disease.

10. Any other serious active disease.

11. Any positive test result for hepatitis B or hepatitis C virus during screening
indicating acute or chronic infection. Latent hepatitis B with undetectable viral load
by PCR is allowable provided appropriate anti-viral prophylaxis is given as per
institutional guidelines.

12. Any positive test for human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS).

13. Any history of severe hypersensitivity reactions to other monoclonal antibodies.

14. A history of allergy or intolerance (unacceptable AEs) to study drug components or
Polysorbate-80-containing infusions.

15. Medical or psychiatric conditions that compromise the patient's ability to give
informed consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2027
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Grampians Health - Ballarat
Recruitment hospital [2] 0 0
Eastern Health - Box Hill
Recruitment hospital [3] 0 0
University Hospital Geelong, Barwon Health - Geelong
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Ballarat
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
- Geelong
Recruitment postcode(s) [4] 0 0
3078 - Heidelberg
Recruitment postcode(s) [5] 0 0
- Perth

Funding & Sponsors
Primary sponsor type
Other
Name
Olivia Newton-John Cancer Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Austin Health
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Grampians Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Fiona Stanley Hospital
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Eastern Health
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Barwon Health
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Commercial sector/Industry
Name [6] 0 0
Bristol-Myers Squibb
Address [6] 0 0
Country [6] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
First line treatment with combination rituximab and BMS-986369 with, or without nivolumab, in
patients in previously untreated Follicular Lymphoma
Trial website
https://clinicaltrials.gov/ct2/show/NCT05788081
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eliza Hawkes, MBBS
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
Alexandra Romano
Address 0 0
Country 0 0
Phone 0 0
0394963573
Fax 0 0
Email 0 0
trials@onjcri.org.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05788081