A Study to Compare the Efficacy and Safety of Golcadomide Plus R-CHOP vs Placebo Plus R-CHOP in Participants with Previously Untreated High-risk Large B-cell Lymphoma
Scientific Title of Study
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Comparing the Efficacy and Safety of Golcadomide Plus R-CHOP Chemotherapy vs Placebo Plus R-CHOP Chemotherapy in Participants with Previously Untreated High-risk large B-cell Lymphoma (GOLSEEK-1)
Trial Acronym
GOLSEEK-1
Secondary IDs if Any
Secondary ID
Identifier
2023-510178-15
EudraCT
CA0731020 Version No. 01 Protocol Date 15-Feb- 2024
Protocol Number
U1111-1300-8493
UTN
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Shilpi Sinha
Designation
Associate Director, Country Head RCO India
Affiliation
Bristol Myers Squibb India Pvt. Ltd.
Address
Bristol Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA, India
Mumbai MAHARASHTRA 4000013 India
Phone
02266288600
Fax
Email
Shilpi.Sinha@bms.com
Details of Contact Person Scientific Query
Name
Shilpi Sinha
Designation
Associate Director, Country Head RCO India
Affiliation
Bristol Myers Squibb India Pvt. Ltd.
Address
Bristol Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA, India
Mumbai MAHARASHTRA 4000013 India
Phone
02266288600
Fax
Email
Shilpi.Sinha@bms.com
Details of Contact Person Public Query
Name
Shilpi Sinha
Designation
Associate Director, Country Head RCO India
Affiliation
Bristol Myers Squibb India Pvt. Ltd.
Address
Bristol Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA, India
Mumbai MAHARASHTRA 4000013 India
Phone
02266288600
Fax
Email
Shilpi.Sinha@bms.com
Source of Monetary or Material Support
Bristol-Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1,Senapati Bapat Marg, Elphistone (W), Mumbai- 400013, India
Primary Sponsor
Name
Bristol Myers Squibb India Pvt. Ltd.
Address
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA,
India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Austria Brazil Chile China France Germany Japan Poland Republic of Korea Romania Spain Taiwan United States of America India Belgium Denmark Italy Netherlands Switzerland United Kingdom
Sites of Study
No of Sites = 8
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Deepam Pushpam
All India Institute Of Medical Sciences (AIIMS)
Dr. B .R A. Institute Rotary Cancer Hospital, All India Institute Of Medical Sciences (AIIMS), Ansari Nagar East, New Delhi-110029- India New Delhi DELHI
09650629370
deepampushpam@gmail.com
Dr Arun Raja Gopal Warrier
Aster Medcity- Kochi
Aster Medcity- Kochi, Ground Floor, Tower 3, Aster DM Healthcare, Kuttisahib road, Near Kothad Bridge, South Chottor P.O, Cheranellor Kochi 682027, Kerala, India Kottayam KERALA
09400515000
drarun.warrier@asterhospital.com
Dr Rohan Bhise
KLES Dr Prabhakar Kore Hospital & Medical Research Center
KLES Dr Prabhakar Kore Hospital & Medical Research Center, OPD- Medical Oncology, G+3 Floor, Nehru Nagar, Belagavi-590010, Karnataka, India Belgaum KARNATAKA
09448866712
rohanbhise30@gmail.com
Dr Vivek Agarwala
Narayana Super speciality Hospital
Narayana Super speciality Hospital, 120/1, Andul Road, Howarh-711103, West Bengal, India Haora WEST BENGAL
08879222875
drvivekagarwala@gmail.com
Dr Narendra Agrawal
Rajiv Gandhi Cancer Institute and Research Centre
Rajiv Gandhi Cancer Institute and Research Centre,
Department of Hemato Oncology & Bone Marrow Transplant,
Rajiv Gandhi Cancer Institute & Research Centre, Sector-5, Rohini, Delhi-110085, India New Delhi DELHI
09650629370
narendra_ag1@rediffmail.com
Dr Javvid Muzamil
Super Speciality Hospital (GMC)
Department of Medical Oncology, Govt. Super Speciality Hospital (GMC), Srinagar - 190010, Jammu & Kashir India Srinagar JAMMU & KASHMIR
07006787372
javvidmd@gmail.com
Dr Arijit Nag
Tata Medical Center
Tata Medical Center,
Clinical hematology & Cellular therapies, 14 MAR (E/W) Newtown, Rajarhat, Kolkata-700160, India Kolkata WEST BENGAL
09051121161
arijit.nag@tmckolkata.com
Dr Bhausaheb P Bagal
Tata Memorial Hospital
Tata Memorial Hospital
(Tata Memorial Centre), Adult Hematolymphoid Department, Main building, ground floor, room no 81,
Dr Ernest Borges Marg, Parel, Mumbai-400012,
Maharashtra, India Mumbai MAHARASHTRA
09930428999
bagalbp@gmail.com
Details of Ethics Committee
No of Ethics Committees= 8
Name of Committee
Approval Status
Instiutional Ethics Committee, KLE Academy of Higher Educationand Research (KAHER)
Approved
Institute Ethics Committee All India Institute Of Medical Sciences
Approved
Institutional Ethics Committee - Super Speciality Hospital (GMC)
Submittted/Under Review
Institutional Ethics Committee, Aster Medcity
Approved
Institutional Review Board Tata Medical Center
Approved
Institutional Review Board, Rajiv Gandhi Cancer Institute and Research Centre
(1) ICD-10 Condition: C858||Other specified types of non-Hodgkin lymphoma,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Golcadomide(BMS-986369/CC-99282) Plus R-CHOP
1) Drug: Golcadomide,
Route of Administration: PO,
Intervention Dose: 0.4mg once daily,
Dosing Day(s)(21-day cycle): 1-7
2)Drug: Rituximab
Route of Administration: IV/SC
Intervention Dose:375 mg/m2 (IV) or 1400 mg (SC)
Dosing Day(s)(21-day cycle): 1
3) Drug: Cyclophosphamide
Route of Administration: IV
Intervention Dose:750 750 mg/m^2
Dosing Day(s)(21-day cycle): 1
4) Drug: Doxorubicin
Route of Administration: IV
Intervention Dose:50 mg/m^2
Dosing Day(s)(21-day cycle): 1
Vincristine
Route of Administration: IV
Intervention Dose:1.4 mg/m2 (max of 2.0 mg total)
Dosing Day(s)(21-day cycle): 1
5) Drug: Prednisone/Prednisolone (Day 1 IV administration is acceptable) a
Route of Administration: PO
Intervention Dose:100 mg
Dosing Day(s)(21-day cycle): 1-5
Abbreviations: IV, intravenous; PO, by mouth; R-CHOP, rituximab, doxorubicin, vincristine, cyclophosphamide,
and prednisone; SC, subcutaneous.
a: Prednisolone IV products to be sourced locally by sites.
Comparator Agent
Placebo Plus R-CHOP
1) Drug: Placebo
Route of Administration: PO
Intervention Dose: Once daily
Dosing Day(s)(21-day cycle): 1-7
2)Drug: Rituximab
Route of Administration: IV/SC
Intervention Dose: 375 mg/m 2 (IV) or 1400 mg (SC)
Dosing Day(s)(21-day cycle): 1
3)Drug: Cyclophosphamide
Route of Administration: IV
Intervention Dose: 750 mg/m 2
Dosing Day(s)(21-day cycle): 1
4)Drug: Doxorubicin
Route of Administration: IV
Intervention Dose: 50 mg/m 2
Dosing Day(s)(21-day cycle): 1
5)Drug: Vincristine
Route of Administration: IV
Intervention Dose: 1.4 mg/m 2 (max of 2.0 mg total)
Dosing Day(s)(21-day cycle): 1
6)Drug: Prednisone/Prednisolone (Day 1 IV administration is acceptable) a
Route of Administration: PO
Intervention Dose: 100 mg
Dosing Day(s)(21-day cycle): 1-5
Abbreviations: IV, intravenous; PO, by mouth; R-CHOP, rituximab, doxorubicin, vincristine, cyclophosphamide, and prednisone; SC, subcutaneous.
a: Prednisolone IV products to be sourced locally by sites.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
A) · Participant has histologically confirmed (per local evaluation) diagnosis of de novo, previously untreated LBCL according to 2022 WHO classification including:
1) DLBCL, NOS (including GCB and ABC types)
2) High-grade B-cell lymphoma, with MYC and BCL2 rearrangements
3) High-grade B-cell lymphoma, NOS
4) T-cell/histiocyte/rich large B-cell lymphoma (THRLBCL)
5) EBV plus DLBCL
B) · Participant has:
1) IPI score 1 or 2 with LDH more than equal to 1.3 x ULN and/or bulky disease defined as single lesion of more than equal to 7 cm OR IPI more than equal to 3
2) Measurable disease defined by at least 1 FDG-avid lesion for FDG-avid subtype and 1 bi- dimensionally measurable (more than 1.5 cm in longest diameter) disease by CT or MRI, as defined by the Lugano classification.
3) Participants must have Ann Arbor Stage II-IV disease
ExclusionCriteria
Details
1) · Participant has any significant medical condition, active infection,
laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.
2) · Participant has any other subtype of lymphoma. Cases of PMBCL, primary cutaneous DLBCL-leg type, Grade 3b FL, FL transformed to a-BCL, ALK-positive large B-cell lymphoma, PEL, Burkitt lymphoma are excluded.
3) · Participant has documented or suspected CNS involvement by lymphoma.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
To evaluate the efficacy of golcadomide plus R-CHOP vs placebo-R-CHOP in participants with untreated high-risk large B-cell lymphoma with respect to PFS as assessed by the investigator.
At baseline, 24 Months and until Progression free survival up to 5 years or study achieves endpoints
Secondary Outcome
Outcome
TimePoints
To evaluate the efficacy of golcadomide plus
R-CHOP vs placebo-R-CHOP
1) OS defined as the time from randomization to death
from any cause
2) Baseline cycle 4 day 1 & cycle6 day 8, End of treatment visit.
To evaluate the efficacy of golcadomide plus
R-CHOP vs placebo-R-CHOP in participants
with untreated high-risk large B-cell lymphoma
with respect to EFS as assessed by the
Investigator
1) Death, disease progression or relapse, initiation of subsequent systemic anti-lymphoma therapy,biopsy-proven disease after end of treatment
2)Baseline cycle 4 day 1 & cycle6 day 8, End of treatment visit.
evaluate the efficacy of golcadomide plus
R-CHOP vs placebo-R-CHOP in participants
with untreated high-risk large B-cell lymphoma
with respect to CMR as assessed by the IRAC
1) Complete metabolic response per IRAC defined as participant achieving CMR at EOT as assessed by IRAC based on the Lugano response criteria
2) Baseline cycle 4 day 1 & cycle6 day 8, End of treatment visit.
To evaluate the efficacy of golcadomide plus
R-CHOP vs placebo-R-CHOP in participants
with untreated high-risk large B-cell lymphoma
with respect to MRD negativity at EOT.
1) MRD negativity defined as participant having undetectable ctDNA levels at EOT.
2) Baseline cycle 4 day 1 & cycle6 day 8, End of treatment visit.
Target Sample Size
Total Sample Size="850" Sample Size from India="32" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
28/02/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
24/06/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="5" Months="1" Days="1"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
This randomized, Phase 3 study has been designed as an add-on placebo-controlled study where golcadomide has been added to the established standard of care (SOC), which is R-CHOP in the experimental arm while placebo in combination with R-CHOP will comprise the control arm. For almost 2 decades, R-CHOP chemotherapy has remained the standard of care for untreated LBCL patients. The chemotherapy regimen and dosing for CHOP was established in the 1970s, and the addition of the anti-CD20 monoclonal antibody rituximab (R) was approved in 2006 based on 3 large, randomized studies, which consistently demonstrated a survival benefit in favor of the R-CHOP combination. Since then, multiple clinical trials have sought to improve upon R-CHOP in the 1L setting. Unfortunately, all failed to demonstrate improved outcomes compared to R-CHOP alone. Recently, however polatuzumab in combination with rituximab, cyclophosphamide, doxorubicin and prednisone (pola-R-CHP) was approved in the US and EU for the treatment of adult patients with untreated DLBCL, NOS or HGBL, and an IPI score of 2 or greater based on the results from the Phase 3 POLARIX study. Additionally, based on these results, pola-R-CHP was recently made a category 1 recommendation alongside R-CHOP for the first-line treatment of patients with LBCL in the National Comprehensive Cancer Network (NCCN) guidelines.