Clinical trial NCT06271057: Golcadomide Post-CAR T-cell in R/R Aggressive Large B-cell Lymphoma Patients With High Risk of Relapse
Official title: Golcadomide (BMS-986369) Post-CAR T-cell in R/R Aggressive Large B-cell Lymphoma Patients With High Risk of Relapse
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma Refractory
Refractory Primary Mediastinal Large B-Cell Lymphoma
Refractory Transformed B-cell Non-Hodgkin Lymphoma
Refractory High Grade B-Cell Lymphoma
Keywords: eligible for CAR T-cells therapy
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Lymphoma Study Association
First posted: 2024-02-21
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Complete metabolic response rate (CMR rate)
timeFrame: 3 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: at 1 month, 3 months, 6 months, 1 year and 2 years, from CAR-T infusion
measure: Objective response rate (ORR)
timeFrame: at 1 month and 3 months
measure: Complete response rate (CRR)
timeFrame: at 1 Month, 6 Months, 1 year, and 2 years
measure: Duration of response (DR)
timeFrame: 2 years
measure: Event-free survival (EFS)
timeFrame: 2 years
measure: Progression-free survival (PFS)
timeFrame: 2 years
measure: Time To Next anti-Lymphoma Treatment (TTNLT)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
measure: Incidence of Adverse Events and Serious Adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: Chu Dijon Bourgogne
city: La Tronche
country: France
facility: Chu de Grenoble
city: Lille
country: France
facility: Chru de Lille
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Chu de Montpellier
city: Nantes
country: France
facility: Chu de Nantes
city: Paris
country: France
facility: Hopital Saint-Louis
city: Pessac
country: France
facility: Chu de Bordeaux
city: Rennes
country: France
facility: Chu Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Toulouse
country: France
facility: Iuct Oncopole
city: Vandœuvre-lès-Nancy
country: France
facility: Chu Brabois
Study officials:
affiliation: Hôpital Saint-Louis
name: Catherine THIEBLEMONT, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Paoli-Calmettes
name: Gabriel BRISOU, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bordeaux
name: François-Xavier GROS, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: