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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

31 Jul 2024 → ongoing

Decision date (initial)

2024-07-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Celgene Corporation

External identifiers

EU CT number

2023-510178-15-00

WHO UTN

U1111-1300-8493

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacokinetic, Safety

To evaluate Progression-Free Survival (PFS). This is the amount of time from when the study starts until the cancer gets worse or the person passes away, whichever happens first.

Secondary objectives 4

1. To evaluate the efficacy of golcadomide + RCHOP versus placebo + RCHOP regarding the Overall Survival (OS). This is the amount of time from when the study starts until the person passes away.
2. To evaluate ’the Event-Free Survival (EFS). This is the amount of time from when the study starts until one of the following things happens: the person passes away, the cancer gets worse or comes back, the person starts a new treatment for their lymphoma, or if the person has any signs of the disease after the treatment ends.
3. To evaluate the Complete Metabolic Response (CMR). This means that at the end of the treatment, the person's body shows no signs of the cancer when we do tests.
4. To evaluate the Minimal Residual Disease (MRD) negativity. This means that at the end of the treatment, we can't find any traces of the cancer in the person's blood.

Conditions and MedDRA coding

High-risk Large B-cell Lymphoma

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Signed Written Informed Consent
2. Type of Participant and Target Disease Characteristics • Histologically confirmed (per local evaluation) diagnosis of de novo, previously untreated LBCL according to 2022 WHO classification including: i) DLBCL, NOS (including GCB and ABC types) ii) High-grade B-cell lymphoma, with MYC and BCL2 rearrangements (HGBL-MYC/BCL2 double hit lymphoma) iii) High-grade B-cell lymphoma, NOS iv) T-cell/histiocyte/rich large B-cell lymphoma v) Epstein-Barr virus + DLBCL • Participant has: i) IPI score 1 or 2 with LDH > 1.3 x ULN and/or bulky disease defined as single lesion of ≥ 7 cm OR ii) IPI ≥ 3 • At least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dimension as measured by CT. • ECOG PS of 0, 1, or 2. ECOG PS 3 is allowed if it is disease related and not due to comorbidities. • Ann Arbor Stage II-IV disease. • Absolute neutrophil count (ANC) ≥ 1.0 × 109/L and Platelets (PLT) ≥ 75 × 109/L unless due to lymphoma. • Hemoglobin ≥ 75 g/L. • Aspartate aminotransferase (AST)/ serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvic transaminase (SGPT) ≤ 2.5 × ULN. In case of documented liver involvement by lymphoma, ALT/SGPT and AST/SGOT must be ≤ 5.0 × ULN. • Serum total bilirubin ≤ 1.5 × ULN. In case of documented liver involvement by lymphoma, serum total bilirubin must be ≤ 3.0 × ULN. For cases of Gilbert syndrome, then serum total bilirubin ≤ 5 × ULN. • Estimated serum creatinine clearance (CrCl) of ≥ 30 mL/min using the modification of diet in renal disease (MDRD) formula The same CrCl cutoff applies in case of documented renal involvement by lymphoma. • Agree to receive pregnancy counseling and adhere to all requirements defined in the Pregnancy Prevention Program • Willing and able to adhere to the study visit schedule and other protocol requirements.
3. Participant must be 18 to 80 years of age

Exclusion criteria 6

1. Medical Conditions a) Participant has any significant medical condition, active infection, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study. b) Participant has any other subtype of lymphoma. • Cases of primary mediastinal (thymic) large B-cell lymphoma • Primary cutaneous DLBCL-leg type, • Grade 3b follicular lymphoma (FL), • indolent lymphoma transformed to LBCL, • ALK-positive large B cell lymphoma, • primary effusion lymphoma, or • Burkitt lymphoma are excluded. c) CNS involvement at diagnosis. d) Participant has persistent diarrhea or malabsorption ≥ Grade 2 (despite medical management). e) Peripheral neuropathy ≥ Grade 2 f) Participant has impaired cardiac function or clinically significant cardiac disease. g) Any other prior malignancy unless being free of the disease for ≥ 3 years; other than Localized nonmelanoma skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor Node Metastasis staging system) or prostate cancer that has been treated with curative intent. v)History of other early-stage malignancy appropriately treated with curatively intent that does not confound study results. Such cases should be discussed with the Medical Monitor
2. Individuals who are breastfeeding
3. Prior/Concomitant Therapy a) Inability to comply with restrictions and prohibited treatments b) Participant is on chronic systemic immunosuppressive therapy or corticosteroids c) Current treatment with strong cytochrome P450 3A4/5 (CYP3A4/5) modulators. ) The washout period for strong CYP3A4/5 modulators is 7 days or 5 half-lives (whichever is longer) before initiation of golcadomide. d) Unwilling to take venous thromboembolism (VTE) prophylaxis. e) Received live attenuated vaccines or live coronavirus disease 2019 (COVID-19) vaccines within 30 days prior to initiation of study treatment.
4. Physical and Laboratory Test Findings a) Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, b) Seropositivity for or active viral infection with human immunodeficiency virus (HIV). c) Chronic active hepatitis B or C infection. d) Condition including the presence of laboratory test result abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study. e) Participant had major surgery ≤ 2 weeks prior to starting golcadomide; f) Participant has any condition causing inability to swallow tablets.
5. Allergies and Adverse Drug Reactions a) Known allergy/hypersensitivity to any component (including excipients) of the study intervention or related compounds or significant drug allergy b) Known hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab. c) Known hypersensitivity to any component of CHOP regimen. d) Known allergy to thalidomide, pomalidomide, or lenalidomide.
6. Other Exclusion Criteria Participation in another clinical trial concurrent with this study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the PFS. This is the time from when a person starts the trial until their disease gets worse or they pass away, whichever happens first.

Secondary endpoints 4

1. To evaluate the OS. This is the time from when a person starts the trial until they pass away from any cause.
2. To evaluate the EFS. This is the time from when a person starts the trial until one of the following happens: they pass away, their disease gets worse or comes back, they start a new treatment for their lymphoma, or they show signs of disease after finishing the treatment.
3. To evaluate the CMR. This means that at the end of the treatment, the person's disease has completely responded to the treatment.
4. To evaluate the MRD negativity. This means that at the end of the treatment, we can't detect any cancer DNA in the person's body.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 8

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 15

Locations

17 EU/EEA countries · 104 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Urgent safety measures 1 · Art. 54 CTR

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 218 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

19 submissions — initial application plus substantial / non-substantial modifications