Health Condition 1: C817- Other Hodgkin lymphoma
Conditions
Interventions
Intervention1: Golcadomide (BMS-986369/CC-99282) + Rituximab: Golcadomide: 0.4 mg orally once daily, Days 1 14 of each 28-day cycle, for up to 12 cycles.
Rituximab:
Cycle 1: 375 mg/m IV at Day 1, the
Sponsors
Celgene Corporation
Eligibility
Inclusion criteria
Inclusion criteria: Signed Written Informed Consent 1) Participants must have signed and dated an IRB or IEC approved written ICF in accordance with regulatory, local, and institutional guidelines. This ICF must be obtained before performing any protocol-related procedures that are not part of normal patient care. Type of Participant and Target Disease Characteristics 2) Participant has histologically confirmed FL (Grade 1, 2, or 3a) as assessed by local pathology. Adequate fresh tumor biopsy tissue or archived tumor biopsy (preferably from the latest relapse if available) with corresponding pathology report for retrospective central pathology confirmation of relapse, is required. Evaluation from fine needle aspirate is not permitted. a) Participant must meet criteria based on investigator assessment to receive systemic therapy. b) Participant must have relapsed or refractory disease, as assessed by the investigator and defined below i) Relapsed FL is defined as relapse after an initial response of CR or PR to the most recent prior therapy. ii) Refractory FL is defined as best response of SD or progressive disease to the most recent prior therapy. 3) Participant has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of lesser than or equal to 2, ECOG PS 3 is allowed if it is lymphoma-related and not due to comorbidities. 4) Participant must have positron emission tomography (PET)-positive disease with at least one PET-positive lesion and measurable disease on cross section imaging by CT, as defined by the Lugano Classification. 5) Participant has received at least 1 or more prior lines of systemic therapy with one line consisting of a combination including an anti-CD20 monoclonal antibody (eg, rituximab, obinutuzumab) and an alkylating agent (eg, cyclophosphamide, bendamustine). Prior treatment with radiation therapy does not count as a line of therapy for eligibility. 6) Participants with an indication for anti-lymphoma treatment as per investigator assessment based on one of the following criteria(modified GELF criteria), but not limited to: a) Bulky disease defined as a nodal or extra nodal (except spleen) mass greater than 7 cm in its greater diameter or, involvement of at least 3 nodal or extra nodal sites (each with a diameter greater than greater than 3 cm) b) Presence of at least one of the following B symptoms i) Fever (greater than 38 C) of unclear etiology ii) Night sweats iii) Weight loss greater than 10 percent within the prior months c) Splenomegaly with inferior margin below the umbilical line d) Any one of the following cytopenia due to lymphoma: i) Platelets less than 100,000 cells per mm3 (100 into 109perL) ii) Absolute neutrophil count (ANC) less than 1,000 cells per mm3 (1.0 into 109per L) iii) Hemoglobin less than 10gperdL (6.25 mmolperL) e) Pleural or peritoneal serous effusion (irrespective of cell content) f) Any compressive syndrome (for example but not restricted to ureteral, orbital, gastrointestinal) 7) Participant must have the following laboratory values: a) Absolute neutrophil count greater than or equal to 1,000 cells/mm3 (1.0 into 109 perL) or greater than or equal 0.5 into 109 perL in case of documented bone marrow involvement by lymphoma or hypersplenism secondary from spleen involvement by lymphoma, without growth factor support for 7 da
Exclusion criteria
Exclusion criteria: Medical Conditions 1) Evidence or history of composite DLBCL and FL or of transformed NHL or any other indolent lymphoma. 2) Follicular large cell as per 5th World Health Organization (WHO) sub-classification (grade 3b FL per WHO 4th classification) or duodenal type FL. 3) Participant has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from compliantly participating in the study based on Investigator s judgment. 4) Participant has any condition that confounds the ability to interpret data from the study based on Investigator s or Sponsor s judgment. 5) Presence or history of central nervous system (CNS) involvement by lymphoma. 6) History of stroke or intracranial hemorrhage within 6 months prior to enrollment. 7) Deep venous thrombosis or Pulmonary embolism within 1 month prior to enrollment. 8) Participants with a history of progressive multifocal leukoencephalopathy. 9) Participant has any other subtype of lymphoma. 10) Participant has persistent diarrhea or malabsorption greater than or equal to Grade 2 (NCI CTCAE v5.0), despite medical management. 11) History of another primary malignancy that has not been in remission for greater than or equal to 3 years except for the following non-invasive malignancies: a) Basal cell carcinoma of the skin. b) Squamous cell carcinoma of the skin. c) Carcinoma in situ of the cervix. d) Carcinoma in situ of the breast. e) Incidental histologic finding of prostate cancer (T1a or T1b using the TNM tumor nodes, metastasis clinical staging system) or prostate cancer that is curative. f) Other completely resected Stage 1 solid tumor that have been treated with curative and have a low risk for recurrence as per the treating investigator. Reproductive Status 12) Individuals who are breastfeeding 13) Individuals who are pregnant Prior/Concomitant Therapy 14) Inability to comply with restrictions and prohibited treatments as listed in Section 7.7 Concomitant Therapy. 15) Participants who are refractory to both chemotherapies as well as lenalidomide, defined as: SD or progressive disease as best response to CHOP and Bendamustine based immunochemotherapy or a response to CHOP and Bendamustine based immunochemotherapy that lasted less than 6 months AND SD or progressive disease as best response to lenalidomide based regimen or a response to lenalidomide based regimen that lasted less than 6 months Note Participants previously refractory to lenalidomide andor exposed will not be randomized in the R-Lenalidomide arm participants who are refractory to R-Chemotherapy (both CHOP and Bendamustine) will not be randomized to R-Chemotherapy arm. 16) Participant is on chronic systemic immunosuppressive therapy or corticosteroids (prednisone or equivalent not exceeding 10 mg per day within the last 4 weeks is allowed) stable use of inhaled or topical corticosteroids is allowed. 17) Participant has current treatment with strong cytochrome P450 3A4or5 (CYP3A4or5) inhibitors or inducers (see corresponding Section 7.7.1). The washout period for strong CYP3A4or5 inhibitors or inducers is 7 days or 5 half-lives (whichever is longer) before initiation of golcadomide. Co-adminsitration of moderate cytochrome P450 3A4or5 (CYP3A4or5) inhibitors or inducers may be permitted after discuss
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival (PFS) per IRAC is defined as the time from randomization to the first disease progression based on Lugano 2014classification guidelines as assessed by IRAC or death from any cause, whichever occurs earlierTimepoint: Up to approximately 32 Months | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response (OR) per IRAC is achieved if a participantachieves an objective partial response (PR) or better during the study based on Lugano 2014 classification guidelines as assessed by IRACTimepoint: OR per IRAC will be analyzed using the Miettinen and Nurminen (M&N) method with stratification factors as factorsamong all randomized participants. Missing data will be imputed with the worst possible values (non-responder). The estimate of difference in OR proportions together with its 95% confidence interval will be reported;Overall Survival (OS) is defined as the time from randomization to time of death due to any causeTimepoint: Same method as that used for the primary endpoint PFS per IRAC;Progression-free survival (PFS) per investigator is defined as the time from randomization to the first disease progression based on Lugano 2014 classification guidelines asassessed by theinvestigatoror death from any cause, whichever occurs earlierTimepoint: The PFS function for each treatment group will be estimated using the KM method;Overall Response (OR) per investigator is achieved if a participantachieves an objective partial response (PR) or better during the study based on Lugano 2014 classification guidelines as assessed bytheinvestigatorTimepoint: The estimate of difference in proportions together with its two-sided 95% confidence interval will be reported.;Complete Metabolic Response (CMR) per investigatoris achieved if a participantachieves a complete metabolic response during the study based on Lugano 2014 classification guideline as assessed by the investigatorTimepoint: The estimate of difference in proportions together with its two-sided 95% confidence interval will be reported.;Duration of Response (DoR) is defined as the time from first response (CR or PR) to the first disease progression based on Lugano 2014 classification guidelines, start of new anti-lymphoma therapy or death from any cause, wh | — |
Countries
Australia, Brazil, Canada, Chile, China, Democratic People's Republic of Korea, Finland, France, Germany, Greece, India, Italy, Japan, Netherlands, Poland, Saudi Arabia, Spain, Turkey, United Arab Emirates, United Kingdom, United States of America
Contacts
Public ContactShilpi Sinha
Bristol-Myers Squibb India Pvt. Ltd.
Outcome results
None listed