Health Condition 1: C822- Follicular lymphoma grade III, unspecified
Conditions
Interventions
Intervention1: Arm A (Investigational Arm without maintenance):: Treatment with surovatamig plus rituximab during the induction period for a total of 7 treatment cycles
(1 cycle = 28 days) followed by
If participants do not achieve CR or PR at the end of Cycle 7, they will enter the post-treatment period aligned with Arm A.
Surovatamig and Rituximab will be administered intravenously
total duratio
if participant achieves CR or PR at the end of Cycle 6, maintenance period = rituximab only every 2 cycles from Cycle 7 to 30 (1 cycle = 28 days)
- R-CHOP: Induction period = Cycle 1 - 6 (1 cycle = 2
if participant achieves CR or PR at the end of Cycle 6, maintenance period = rituximab only every 2 cycles from Cycle 7 to 30 (1 cycle = 28 days)
- B-R: Induction period = Cycle 1 - 6 (1 cycle = 28 d
maintenance period = rituximab only every 2 cycles from Cycle 7 to 30 (1 cycle = 28 days)
Cyclophosphamide, Vincristine, Doxorubicin and Bendamustine will be administered intravenously. prednisolone
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion criteria Participants are eligible to be included in the study only if all pre specified criteria are met. Eligibility criteria for the Safety Run In period and Phase III parts are the same unless otherwise specified 1. Capable of giving signed informed consent as described in Appendix A, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol 2. Provision of signed and dated, written informed consent prior to any mandatory study specific procedures, sampling, and analyses 3. For participants who agree to the optional genetic testing, provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative 4. Participant must be at least 18 years of age, inclusive, at the time of signing the ICF. 5. Histologically confirmed diagnosis of classic FL per WHO 2022 classification, as assessed by Investigators. Local histopathologic confirmation is sufficient to confirm eligibility. 6. Stage II to IV disease Phase III portion only. For SRI, all Stages are allowed. 7. FLIPI score 2 to 5 Phase III portion only. For SRI, all FLIPI scores are allowed. 8. ECOG performance status of 0 to 2 (Appendix G) 9. Previously untreated disease (no prior systemic lymphoma-directed therapies) 10. Need for systemic treatment based on the presence of at least one of the following GELF criteria (Brice et al, 1997): (a) At least one lesion with diameter Greater than or equal 7.0 cm (b) At least 3 nodal sites, each with a diameter of Greater than or equal 3.0 cm (c) Presence of at least one of the following B symptoms (i) unexplained fevers (ii) night sweats (iii) unintentional weight loss greater than 10% within the prior 6 months (d) Symptomatic splenomegaly (e) Pleural effusions or peritoneal ascites (f) Any one of the following cytopenias due to lymphoma (i) Haemoglobin less than 10 g or dL (6.25 mmol or L) (ii) Platelets less than 100 multiplied by by 109L (iii) ANC less than 1.5 multiplied by by 109L (g) Risk of organ compression or dysfunction due to disease 11. FDG avid and measurable disease. Defined as at least one bi-dimensionally measurable nodal lesion (defined as greater than 1.5 cm in its longest dimension), or at least one bi dimensionally measurable extranodal lesion (defined as greater than 1.0 cm in its longest dimension). 12. Adequate liver function: total bilirubin less than 1.5 multiplied by ULN (or less than or equal 3 x ULN in presence of Gilbert s syndrome). AST and ALT must be Less than or equal 3 multiplied by ULN (or less than or equal 5 x ULN in presence of lymphoma involvement). 13. Adequate haematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) within 28 days prior to C1D1, including: (a) ANC of Greater than or equal 1.0 multiplied by 109 cells L (b) Platelet count of Greater than or equal 75,000 L (c) Haemoglobin Greater than or equal 9 g dL Transfusion and/or growth factor support is permitted; however, neutrophils, platelets, and haemoglobin must be stable for at least 72 hours after transfusion and/or growth factor administration prior to screening for the participant to be elig
Exclusion criteria
Exclusion criteria: Exclusion Criteria Participants are excluded from the study if any of the following criteria apply: 1. Follicular large B cell lymphoma (WHO 2022 classification), formerly Follicular lymphoma Grade 3B (WHO 2016 classification), or suspicion for histologic transformation to highgrade aggressive lymphoma based on Investigator s assessment. NOTE: Participants with baseline PET scan demonstrating distinct sites with distinctly high SUV should have these areas biopsied to confirm no occult transformation, as per Investigator judgement and if clinically safe feasible (refer to Section 8.2.2) 2. Contraindication to any of the individual components of B R, R CVP, or R CHOP regimens, making a particular combination unfeasible for a patient. A patient can still participate if the subject is eligible to at least one of the remaining combinations. 3. History of or active CNS involvement by lymphoma. 4. The presence of greater than 5000 circulating lymphoma cells ul in the peripheral blood. 5. History of a clinically relevant CNS medical condition or pathology that required treatment in the preceding year, is currently symptomatic or that which the treating investigator considers to have the potential to interfere with the evaluation of safety such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, neurodegenerative disorder including Parkinson s disease, cerebellar disease, organic brain syndrome,or Psychosis. 6. History of or active autoimmune disease involving the CNS. 7. Participants who have any concurrent or history of malignancy within 2 years prior to C1D1, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (eg, 5 year OS rate greater than 90percent), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer (a) Participants who have prostate cancer with no evidence of metastatic disease and are not on active therapy except for anti-androgen therapy may be allowed study Entry. (b) Participants with early stage breast cancer, receiving hormonal therapy in the adjuvant setting after curative surgery, may be allowed study entry. (c) Participants who have a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are allowed. (d) Participants who have a malignancy that has been in remission without treatment for 2 years prior to the first study intervention administration will be allowed. 8. Has any medical or psychiatric condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities, could interfere with successfulor safe delivery of therapy, or could interfere with evaluation of the study intervention or interpretation of participant safety or study results. 9. Participants with: (a) Active or uncontrolled infection (including EBV) requiring systemic therapy and which places participant at unacceptable risk if he or she were to participate in the study. If a participant has a history of COVID 19 within 1 month of C1D1 or contracts COVID while on study treatment, participant must have 2 consecutive negative tests (PCR testing is preferable) performed at least 48 hours apart prior to resuming dosing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate the superiority of clinical efficacy of surovatamig plus rituximab compared to SOC in participants with untreated FLTimepoint: outcome will be assessed at following time points: At Week 12 ( 1w) and Week 28 ( 2w) post C1D1, thereafter Q16W ( 2w) for next 12 months, then Q24W ( 2w) until Year 5, afterwards as clinically indicated | — |
Secondary
| Measure | Time frame |
|---|---|
| To demonstrate the superiority of surovatamig plus rituximab compared to Investigator s choice of SoC chemoimmunotherapy by evaluation of additional efficacy measures. To demonstrate the Contribution of Phase of surovatamig maintenance after induction period with surovatamig plus rituximab Timepoint: CR at EoI based on Lugano 2014 Response Criteria, as determined by BICR and Investigator assessment at local site. The analysis will include all randomised participants. Data obtained from randomisation up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of CR at EoI, regardless of whether the participant withdraws from therapy. Participants who discontinue treatment without a response or progression, receive a subsequent anti-lymphoma therapy, and then respond will not be included as responders. In the absence of subsequent anti-lymphoma therapy, participants (including those who discontinue therapy) will be followed up for response. The measure of interest is the common risk ratio of CR at EoI. CR rate is defined as the proportion of participants achieving a CR at any time as based on Lugano 2014 Response Criteria as determined by BICR and Investigator assessment at local site. The analysis will include all randomised participants. The measure of interest is the common risk ratio of the CR. ORR at EoI based on Lugano 2014 Response Criteria as determined by Investigator assessment at local site. The analysis will include all randomised participants. The measure of interest is the common risk ratio of CR at EoI. CR rate at 30 months (CR30) based on Lugano 2014 Response Criteria, as determined by BICR and Investigator assessment at local site. The analysis will include all randomised participants. The measure of interest is the common risk ratio of CR30. DoR will be defined as the time from the date of first documented response until date of documented progression based on | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Hong Kong, Hungary, India, Italy, Japan, Norway, Poland, Republic of Korea, Slovakia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States of America
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Ltd
Outcome results
None listed