Golcadomide Post-CAR T-cell in R/R Aggressive Large B-cell Lymphoma Patients With High Risk of Relapse

Golcadomide (BMS-986369) Post-CAR T-cell in R/R Aggressive Large B-cell Lymphoma Patients With High Risk of Relapse

This study is an open-label, multicenter, proof of concept, phase 2 trial. Patients will be recruited over 18 months. Safety analysis will be performed with a stop of the enrollment after 3 patients have either 1 complete treatment cycle or permanently discontinued treatment whichever occurs first.

Approximatively 65 patients with aggressive large B-cell lymphoma (LBCL) (including diffuse large B-cell lymphoma (DLBCL), Primary mediastinal B-cell lymphoma (PMBCL), any transformed follicular or marginal zone lymphoma, high-grade B-cell lymphoma (HGBL)) will be enrolled in the study.

The duration of treatment with golcadomide (CELMoD) is 24 weeks with 6 cycles of 28 days (4 weeks), starting at 5 days after CAR-T cells infusion.

The primary objective of the study is to estimate the efficacy of golcadomide administered post-anti-CD19 CAR T-cell infusion, Efficacy determination will be based upon the primary endpoint of complete metabolic response (CMR) rate at 3 months after infusion of anti-CD19 CAR T-cell assessed by study investigator.

Study Overview

• Status: Not yet recruiting
• Conditions: Refractory High Grade B-Cell Lymphoma; Diffuse Large B-cell Lymphoma Refractory; Refractory Transformed B-cell Non-Hodgkin Lymphoma; Refractory Primary Mediastinal Large B-Cell Lymphoma
• Intervention / Treatment: Drug: golcadomide

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Stéphanie DOYEN; Phone Number: +33 4 27 01 27 36; Email: stephanie.doyen@lysarc.org

Study Locations

• France
  • Créteil, France, 94010
    • Hôpital Henri Mondor
  • Dijon, France, 21000
    • CHU Dijon Bourgogne
  • La Tronche, France, 38700
    • CHU de Grenoble
  • Lille, France, 59037
    • CHRU de Lille
  • Marseille, France, 13273
    • Institut Paoli Calmettes
  • Montpellier, France, 34090
    • CHU de Montpellier
  • Nantes, France, 44093
    • CHU de Nantes
  • Paris, France, 75475
    • Hôpital Saint-Louis
  • Pessac, France, 33604
    • CHU de Bordeaux
  • Rennes, France, 35033
    • CHU Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Toulouse, France, 31059
    • IUCT Oncopole
  • Vandœuvre-lès-Nancy, France, 54511
    • CHU Brabois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient who understood and voluntarily signed and dated an informed consent prior to any study-specific assessments/procedures being conducted
2. Adults patients (≥ 18-year-old at the time of signing the informed consent form; no upper age limit)
3. Eligible for any commercialized market authorized anti-CD19 CAR T-cells
4. Performance Status 0 or 1

5. With aggressive large B-cell lymphoma, including:

   • diffuse large B-cell lymphoma
   • Primary mediastinal B-cell lymphoma
   • Any transformed follicular or marginal zone lymphoma
   • high-grade B-cell lymphoma (HGBL) Note: patients with Central Nervous System (CNS) involvement could be included but not patients with primary CNS lymphoma
6. Available biopsy for centralized review
7. With a CAR T-cells indication as soon as 2nd line treatment no later than in 4th line, previously validated by the multidisciplinary tumor board Note: Any treatment performed prior to leukapheresis is considered a line of treatment
8. Total MetabolicTumor Volume (TMTV) > 80 ml, measured by centralized review, on 18FDG-PET (positron emission tomography) done just before starting CAR T-cells procedure (i.e., D-13 +/- 4 days before CAR-T cells infusion)
9. Creatinine clearance (as estimated by Modification of Diet in Renal Disease (MDRD) if > 60-year-old or Cockcroft-Gault if <60yo) >45 mL/min,

10. Adequate hepatic function:

    • aspartate aminotransferase/alanine aminotransferase (ALT/AST) ≤ 3.0 x ULN. (Note: In the case of documented liver involvement by lymphoma, ALT/AST must be ≤ 5.0 x ULN)
    • Serum total bilirubin ≤ 2.0 mg/dL (34 μmol/L) (Note: In the case of Gilbert's syndrome, or documented liver or pancreatic involvement by lymphoma, serum total bilirubin must be ≤ 3.0 mg/dL (51 μmol/L))
11. Patient covered by any social security system (France)
12. Patient who understands and speaks one of the country official languages, unless local regulation authorizes independent translators

13. Contraception:

    • For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, as soon as consent is signed, during the treatment period (including periods of treatment interruption), and for at least 28 days after the last dose of golcadomide, Women must refrain from donating eggs during this same period.

Exclusion Criteria:

1. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease free for at least 3 years
2. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management; simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the sponsor's medical monitor
3. History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection; subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America guidelines or applicable country guidelines
4. Significant pulmonary function impairment and oxygen saturation (SaO2) < 92% on room air
5. Significant cardiovascular disease such as New York Heart Association Class III or IV or Objective Class C or D cardiac disease (see appendix 07)
6. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment
7. History of severe immediate hypersensitivity reaction to any of the agents used in this study
8. Current treatment with strong CYP3A4/5 modulators (see appendix 13)
9. Pregnant, planning to become pregnant or lactating Women of Child Bearing Potential
10. Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator's decision)
11. Person deprived of his/her liberty by a judicial or administrative decision
12. Person hospitalized without consent
13. Adult person under legal protection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: golcadomide post CAR T-cells; 0.3 mg - Per Os - every week - 6 months	Drug: golcadomide; golcadomide 0.3 mg weekly from D+5 post CAR T-cells administration until D+166; Other Names: BMS-986369; CC-99282

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete metabolic response rate (CMR rate)	efficacy of golcadomide administered post-anti-CD19 CAR T-cell infusion	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	incidence of either a complete (CMR) or a partial (PMR) metabolic response per the Lugano Classification (Cheson 2014) as determined by study investigators	at 1 month, 3 months, 6 months, 1 year and 2 years, from CAR-T infusion
Objective response rate (ORR)	determined by imaging central review	at 1 month and 3 months
Complete response rate (CRR)	percentage of complete response determined by investigator assessment classification	at 1 Month, 6 Months, 1 year, and 2 years
Duration of response (DR)	time from attainment of PMR or CMR to the date of first documented disease progression/relapse (based on investigator disease assessment (INV)) or death from any cause	2 years
Event-free survival (EFS)	the time between CAR T-cells injection and death, disease progression, or start of subsequent new anti-lymphoma therapy including Stem Cell Transplant (SCT)	2 years
Progression-free survival (PFS)	time from CAR T-cells injection to the first observation of documented disease progression/relapse (based on investigator disease assessment (INV)) or death	2 years
Time To Next anti-Lymphoma Treatment (TTNLT)	from the date of CAR T-cells injection to the date of first documented administration of any new anti-lymphoma treatment	2 years
Overall survival (OS)	from date of CAR T-cells injection to the date of death	2 years
Incidence of Adverse Events and Serious Adverse events		2 years

Collaborators and Investigators

• Sponsor: The Lymphoma Academic Research Organisation
• Collaborators: Lymphoma Study Association
• Investigators: Principal Investigator: Catherine THIEBLEMONT, Prof. Dr., Hôpital Saint-Louis; Principal Investigator: Gabriel BRISOU, Prof. Dr., Institut Paoli-Calmettes; Principal Investigator: François-Xavier GROS, Prof. Dr., University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Estimated): April 22, 2024
• Primary Completion (Estimated): January 15, 2026
• Study Completion (Estimated): October 20, 2027

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: eligible for CAR T-cells therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: CARMOD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No