CARMOD - Golcadomide (BMS-986369) post-CAR T-cell in R/R Aggressive large B-cell lymphoma patients with high risk of relapse

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lymphoma Academic Research Organisation

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

14 Jun 2024 → ongoing

Decision date (initial)

2024-04-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

to estimate the efficacy of golcadomide administered post-anti-CD19 CAR T-cell infusion

Secondary objectives 11

1. Objective response rate (ORR): ORR is defined as the 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
2. ORR determined by imaging central review at 1 month and 3 months
3. CMR at 1 Month, 6 Months, 1 year, and 2 years
4. PMR at 1 Month, 3 Months, 6 Months, 1 year, and 2 years
5. Duration of response (DoR)
6. Event-free survival (EFS) including earlier date of progression, start of subsequent new anti-lymphoma therapy including Stem Cells Transplant (SCT), or death from any cause
7. Progression-free survival (PFS) defined from CAR T-cells infusion date to the date of disease progression per the Lugano Classification (Cheson 2014) or death from any cause
8. Time to next anti-lymphoma therapy (TTNLT) including SCT (except SCT done as consolidation post-CART)
9. Overall survival (OS)
10. Incidence of adverse events (AE) and clinically significant changes in safety laboratory values
11. Incidence of cytokine released syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)

Conditions and MedDRA coding

relapsed or refractory patients with aggressive large B-cell lymphoma at high risk of relapse

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Patient who understood and voluntarily signed and dated an informed consent prior to any study-specific assessments/procedures being conducted
2. Adult 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. PS 0, 1 or 2
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 CNS involvement could be included but not patients with primary CNS lymphoma
6. Available biopsy for centralized review Note: if several previous biopsies exist, the last one will be the one to be transmitted. If this biopsy has already been reviewed by LYSARC, the result of this review can be used for this patient
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 and in compliance with marketing authorization
8. TMTV > 80 ml, measured by centralized review, on standard 18FDG-PET (positron emission tomography) done just before starting CAR-T procedure (i.e., before lymphodepletion)
9. Creatinine clearance (as estimated by MDRD if > 60-year-old or Cockcroft-Gault if <60yo > 45 mL/min
10. Adequate hepatic function: 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. 13. Contraception (refer to section 14.7): • For women of childbearing potential (WOCP): Agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one highly effective method, 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. • For men: during the treatment period (including periods of treatment interruption) and for at least 28 days after the last dose of golcadomide, male subjects must: o With female partners of childbearing potential: use a condom associated to a highly effective method of contraception or remain abstinent (refrain from heterosexual intercourse) o With pregnant female partners: use a condom or remain abstinent (refrain from heterosexual intercourse) Men must refrain from donating sperm during this same period.

Exclusion criteria 14

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. Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator’s decision)
3. Person deprived of his/her liberty by a judicial or administrative decision
4. Person hospitalized without consent
5. Adult person under legal protection
6. 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
7. 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
8. History of allogeneic stem cell transplant complicated or not with active acute or chronic GVHD.
9. Current treatment with strong CYP3A4/5 modulators (see appendix 13)
10. Pregnant, planning to become pregnant or lactating WOCBP (See definition section 14.6.1.1)
11. Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator’s decision)
12. Person deprived of his/her liberty by a judicial or administrative decision
13. Person hospitalized without consent
14. Adult person under legal protection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 8

1. Objective response rate (ORR)
2. Complete metabolic response (CMR)
3. Partial metabolic response (PMR)
4. Duration of response (DoR)
5. Event-free survival (EFS)
6. Progression-free survival (PFS)
7. Time to next anti-lymphoma therapy (TTNLT)
8. Overall survival (OS)

Investigational products

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

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lymphoma Academic Research Organisation

Sponsor organisation

Lymphoma Academic Research Organisation

Address

Pavillon 6e, Secteur Sainte Eugenie Secteur Sainte Eugenie

City

Pierre Benite Cedex

Postcode

69495

Country

France

Scientific contact point

Organisation

Lymphoma Academic Research Organisation

Contact name

Catherine THIEBLEMONT

Public contact point

Organisation

Lymphoma Academic Research Organisation

Contact name

Project Management

Sponsor responsibilities

Article 77 compliance

Lymphoma Academic Research Organisation

Contact point sponsor

Lymphoma Academic Research Organisation

Article 77 implementation

Lymphoma Academic Research Organisation

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 11 files

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

Application history

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