Trial Title:
Treatment Of Newly-diagnosed Follicular Lymphoma With CELMoD Golcadomide, Rituximab +/- Nivolumab.
NCT ID:
NCT05788081
Condition:
Follicular Lymphoma Stage II
Follicular Lymphoma Stage III
Follicular Lymphoma Stage IV
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Rituximab
Nivolumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Study Design Open label multicentre umbrella Bayesian Optimal Phase II study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
golcadomide
Description:
BMS-986369 is an orally administered Cereblon-modulating compound
Arm group label:
Arm A- Golcadomide + Rituximab
Arm group label:
Arm B- Nivolumab + golcadomide + Rituximab
Other name:
BMS-986369
Other name:
CC-99282
Intervention type:
Drug
Intervention name:
Nivolumab 10 MG/ML
Description:
Nivolumab is a fully humanised IgG4 blocking monoclonal antibody against PD-1.
Arm group label:
Arm B- Nivolumab + golcadomide + Rituximab
Other name:
Opdivo
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Rituximab is a chimeric anti-CD20 antibody containing human IgG lambda and kappa constant
regions with murine variable regions
Arm group label:
Arm A- Golcadomide + Rituximab
Arm group label:
Arm B- Nivolumab + golcadomide + Rituximab
Other name:
Mabthera
Summary:
First line treatment with combination rituximab and golcadomide with, or without
nivolumab, in patients in previously untreated Follicular Lymphoma
Detailed description:
This study will involve participants with a condition called Follicular Non Hodgkin
Lymphoma (Follicular Lymphoma).
The main purpose of this study is to see if it is safe to give an induction schedule of
the drug golcadomide, in combination with Rituximab +/- Nivolumab, and to see how
effective this combination is in patients who have had no previous drug treatment for
their lymphoma. In particular, we will be monitoring for any specific side effects which
may be increased by adding golcadomide to Rituximab treatment +/- Nivolumab for 8 cycles
(28 days per cycle), with up to 2 years of maintenance treatment of rituximab in eligible
patients following induction.
Participants will be reviewed at baseline and prior to each cycle of treatment for
toxicity, scans will be performed at baseline, after 2 and 5 cycles of induction
treatment, and every 8 weeks during maintenance phase. Following completion of treatment,
participants will be followed up for a total of 3 years (every 6 months). In participants
with relapsed disease, these will be followed for survival every 3 months.
Criteria for eligibility:
Criteria:
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. Measurable FDG avid disease on baseline PET/CT scan.
7. 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).
h) 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.
i) 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) j)
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).
k) Adequate left ventricular ejection fraction of >45% as demonstrated on a Gated Cardiac
Blood Pool Scan or echocardiogram.
l) Life expectancy > 3 months. m) Patients of childbearing potential willing to adhere to
the following contraceptive precautions.
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 golcadomide
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 golcadomide 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.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Grampians Health
Address:
City:
Ballarat
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Geoff Chong, MBBS
Email:
geoff.chong@bhs.org.au
Investigator:
Last name:
Geoff Chong, MBBS FRACP
Email:
Principal Investigator
Facility:
Name:
Eastern Health
Address:
City:
Box Hill
Zip:
3128
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Tamara Marconi, MBBS
Email:
tamara.marconi@monash.edu
Investigator:
Last name:
Tamara Marconi, MBBS
Email:
Principal Investigator
Facility:
Name:
University Hospital Geelong, Barwon Health
Address:
City:
Geelong
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Sonia Gauci
Email:
sonia.gauci@barwonhealth.org.au
Contact backup:
Last name:
Sumita Ratnasingam, MBBS FRACP
Email:
sumita.ratnasingam@barwonhealth.org.au
Investigator:
Last name:
Sumita Ratnasingam, MBBS FRACP
Email:
Principal Investigator
Facility:
Name:
Austin Health
Address:
City:
Heidelberg
Zip:
3078
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Eliza Hawkes, MBBS, FRACP
Phone:
+61394965000
Email:
eliza.hawkes@austin.org.au
Contact backup:
Last name:
Kristen Houdyk, RN
Phone:
+61394965000
Email:
cctc.ethics@austin.org.au
Investigator:
Last name:
Eliza Hawkes, MBBS, FRACP
Email:
Principal Investigator
Investigator:
Last name:
Geoff Chong, MBBS, FRACP
Email:
Sub-Investigator
Facility:
Name:
Fiona Stanley Hospital
Address:
City:
Perth
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Allison Barraclough, MBBS, FRACP
Email:
allison.barraclough@health.wa.gov.au
Investigator:
Last name:
Allison Barraclough, MBBS, FRACP
Email:
Principal Investigator
Start date:
August 31, 2023
Completion date:
June 1, 2027
Lead sponsor:
Agency:
Olivia Newton-John Cancer Research Institute
Agency class:
Other
Collaborator:
Agency:
Austin Health
Agency class:
Other
Collaborator:
Agency:
Grampians Health
Agency class:
Other
Collaborator:
Agency:
Fiona Stanley Hospital
Agency class:
Other
Collaborator:
Agency:
Eastern Health
Agency class:
Other
Collaborator:
Agency:
Barwon Health
Agency class:
Other
Collaborator:
Agency:
Bristol-Myers Squibb
Agency class:
Industry
Source:
Olivia Newton-John Cancer Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05788081
