A Phase 2 Study of Teclistamab in Combination with Daratumumab or Lenalidomide in Elderly Patients with Newly Diagnosed Multiple Myeloma - IFM2021-01

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Lille

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Dec 2023 → ongoing

Decision date (initial)

2024-07-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Janssen-Cilag International N.V.

External identifiers

EU CT number

2024-514101-65-00

EudraCT number

2022-001594-31

ClinicalTrials.gov

NCT05572229

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate the efficacy of Tec-Dara or Tec-Len.

Secondary objectives 3

1. To evaluate the safety and tolerability of Tec-Dara or Tec-Len in patients with newly diagnosed multiple myeloma
2. To further evaluate efficacy of Tec-Dara or Tec-Len
3. To evaluate rate of minimal residual disease (MRD)-negativity

Conditions and MedDRA coding

Multiple Myeloma

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

The data will be shared with Janssen-Cilag International N.V. in its quality of co-processor in order to capture any security element related to the other projects they are sponsoring. All data processing is MR001 compliant. Sharing will be securely performed.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patient must be at least ≥ 65 years of age
2. A documented diagnosis of multiple myeloma according to IMWG diagnostic criteria: Multiple myeloma is defined as clonal bone marrow plasma cells ≥ 10% or biopsy-proven bone or extramedullary plasmacytoma and one or more of the following myeloma defining events: a.Myeloma milestones: i.Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferation disorder, specifically: oHypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) above the upper limit of normal or >2.75 mmol/L (>11 mg/dL) oRenal impairment: creatinine clearance <40 mL per min or serum creatinine >177 μmol/L (>2 mg/dL) oAnemia: hemoglobin value >20 g/l below the lower limit of normal, or hemoglobin value <100 g/lg oBone lesions: one or more osteolytic lesions on skeletal radiograph, CT or PETCT b.One or more of the following biomarkers of malignancy: i.Percentage of clonal bone marrow plasma cells ≥ 60%. ii.Serum involved:uninvolved free light chain ratioe ≥100 iii.>1 focal lesions on MRI studies and : c.Measurable disease on screening, defined by any of the following: i.Serum monoclonal paraprotein (M protein) level ≥ 0.5 g/dL or urine M protein level ≥ 200 mg/24 hours. ii.Light chain multiple myeloma in which the only measurable disease is by serum free light chain (FLC) levels: serum Ig free light chains ≥ 10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio.
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
4. Not considered for high-dose chemotherapy with ASCT.
5. Have clinical laboratory values meeting the following criteria : -Hemoglobin: ≥ 8 g/dL (≥5 mmol/L; without prior CG transfusion within 7 days prior to laboratory test; use of recombinant human erythropoietin is allowed) ; -Platelets: ≥75×10^9 /L in patients in whom <50% of bone marrow nucleated cells are plasma cells and ≥50×10^9 /L in patients in whom ≥50% of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before laboratory test) -Absolute neutrophil count: ≥1.0×109 /L (pre-administration of growth factor is allowed, but wait 7 days for G-CSF or GM-CSF and 14 days for pegylated GCSF ). -AST and ALT: ≤2.5×ULN -eGFR: ≥30 mL/min as calculated by the Cockcroft-Gault formula calculation or creatine clearance measured by 24-hour urine collection. -Total bilirubin: ≤2.0×ULN; except in patients with congenital bilirubinemia, such as Gilbert's syndrome (in which case a direct bilirubin ≤1.5×ULN is required). -Serum calcium corrected for albumin: ≤14 mg/dL (≤3.5 mmol/L) or ionized free calcium ≤6.5 mg/dL (≤1.6 mmol/L )
6. A male patient must wear a condom during any activity that allows passage of ejaculate to another person during the study and a minimum of 4 weeks after the last dose of Lénalidomide or for at least 90 days after receiving the last dose of other study treatment. If the female partner is of childbearing age, she must also practice a highly effective method of contraception. If the male patient is vasectomized, he must always wear a condom (with or without foam/gel/film/cream/spermicidal suppository), but his female partner is not required to use contraception.
7. A male patient must agree not to donate sperm for reproductive purposes a minimum of 4 weeks after the last dose of Lénalidomide or for at least 90 days after receiving the last dose of other study treatment.
8. Each subject must sign an informed consent form (ICF) (or their legally acceptable representative must sign in accordance with local requirements) indicating that they understand the purpose and procedures required for the study and agree to participate.
9. The subject must be willing and able to comply with the prohibitions and restrictions specified in this protocol as outlined in the ICF.

Exclusion criteria 22

1. CNS involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.
2. Plasma cell leukemia at screening, Waldenström macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis.
3. Any ongoing myelodysplastic syndrome or B cell malignancy (other than multiple myeloma).
4. Any history of malignancy, other than multiple myeloma, which is considered at high risk of recurrence requiring systemic therapy.
5. Any active malignancies other than myeloma multiple.
6. Stroke, transient ischemic or seizure within 6 months prior to signing the GSI.
7. Presence of the following cardiac conditions: a. New York Heart Association Stage III or IV congestive heart failure, b.Myocardial infarction or coronary artery bypass surgery ≤6 months prior to enrollment, c.History of clinically significant ventricular arrhythmia or unexplained syncope not thought to be vasovagal in nature or due to dehydration, d.History of severe nonischemic cardiomyopathy.
8. COPD with a FEV1 <50% of predicted normal. Note that FEV1 testing is required for patients with known or suspected of having COPD or asthma and patients must be excluded if FEV1 <50% of predicted normal.
9. Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that FEV1 testing is required for patients known or suspected asthma and patients must be excluded if FEV1 <50% of predicted normal.
10. Radiotherapy within 14 days or focal radiation within 7 days.
11. A maximum cumulative dose of corticosteroids of ≥140 mg of prednisone or equivalent within 14-day period before the first dose of study drug (does not include pretreatment medications).
12. Received a live or attenuated vaccine within 4 weeks before the first dose of study drug. Non live or non-replicating vaccines authorized for emergency use (eg, COVID-19) are allowed.
13. Any prior therapy for multiple myeloma or smoldering myeloma other than a short course of corticosteroids prior to signing ICF (not to exceed 40 mg of dexamethasone, or equivalent per day for a maximum of 4 days, total of 160 mg dexamethasone or equivalent
14. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients
15. HIV positive with 1 or more of the following: a.History of AIDS-defining conditions, b.CD4 count <350 cells/mm3, c.Detectable viral load during screening or within 6 months prior to screening, d.Not receiving highly active anti-retroviral therapy, e.Had a change in antiretroviral therapy within 6 months of the start of screening, f.Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the Medical Monitor.
16. Hepatitis B infection. In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection.
17. Active hepatitis C infection as measured by positive hepatitis C virus (HCV)-RNA testing. Patients with a history of HCV antibody positivity must undergo HCV-RNA testing. If a patient with history of chronic hepatitis C infection completed antiviral therapy and has undetectable HCV-RNA for at least 12 weeks following the completion of therapy, the patient is eligible for the study.
18. Women of childbearing potential.
19. Patient had major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the patient is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment.
20. Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
21. Patient plans to father a child while enrolled in this study or within 90 days after the last dose of study intervention.
22. Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of very good partial response (VGPR) or better according to the IMWG criteria in patients with newly diagnosed multiple myeloma after 4 cycles of treatment with Tec-Dara or Tec-Len.

Secondary endpoints 4

1. ORR, (PR or better) as defined by the IMWG response criteria after 2 cycles of treatment
2. Treatment-emergent adverse events as defined by the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE, version 5.0).
3. - ORR, (PR or better) as defined by the IMWG response criteria. - VGPR or better - Complete response (CR) or better - Time to Response - Duration of response (DOR) - Progression-free survival (PFS) - Overall survival (OS) - Time to treatment failure (time from date of inclusion to discontinuation of treatment for any reason, including death, progression, toxicity) - Time to Next Treatment (TTNT)
4. - MRD negativity (at the 10-5 and 10-6 level by next generation sequencing [NGS]) at 6 months. - Sustained MRD negativity (at the 10-5 and 10-6 level by NGS) at 18 months (12 months after the initial MRD point).

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Lille

Sponsor organisation

Centre Hospitalier Universitaire De Lille

Address

2 Avenue Oscar Lambret, Cs 70001 Cs 70001

City

Lille Cedex

Postcode

59037

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Lille

Contact name

Pr Salomon MANIER - Coordinating Clinical Investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Lille

Contact name

Aomar KEMKEM - Coordonnateur Promotion

Locations

1 EU/EEA country · 30 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

Corrective measures 1 · Art. 77 CTR

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

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