TECLISTAMAB for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements\n- Age between 18 – 80 years regardless of transplant eligibility at the time of inclusion.\n- Patient has documented diagnosis of multiple myeloma according to IMWG diagnostic criteria, with at least one of the following high-risk features: a)High-risk FISH: del(1p), del(17p), t(4;14), t(14;16) and 1q amplifications. b)R-ISS 3. c)Presence of extramedullary disease, defined as presence of paramedullary lesions or extramedullary plasmacytoma.\n- Patient has measurable secretory disease defined as either serum monoclonal protein of ≥ 0.5 g/dL or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/dL (100 mg/L), with an abnormal serum FLC ratio.\n- Human inmunodeficiency virus-positive patients are elegible if they meet all of the following: a. No detectable viral load (ie, < 50 copies/mL) at screening b. CD4+ count > 300 cells/mm3 at screening c. No AIDS defining opportunistic infection within 6 months of screening d. Receiving HAART. Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening.\n- Patient has an ECOG performance status of 0, 1 or 2.\n- Patient must have adequate organ function, defined in: Hemoglobin ≥ 8 g/dL, Platelets ≥ 75 x 109/L in participants in whom <50% of bone marrow nucleated cells are plasma cells and ≥ 50×109/L in participants in whom ≥50% of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test), ANC ≥ 1.0 x 109 /L, ALT and AST ≤ 2.5 x upper limit normal, eGFR ≥30 mL/min based on Modified Diet in Renal Disease Formula calculation or creatine clearance measured by a 24-hour urine collection, Total bilirubin ≤ 1.5 x ULN (isolated total bilirubin ≥ 1.5 x ULN with conjugated [direct] bilirubin < 1.5 x ULN is allowed for those patients Corrected serum calcium ≤14 mg/dL (≤3.5 mmol/L) or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L)\n- A female of childbearing potential must have a negative highly sensitive urine or serum (β human chorionic gonadotropin [β-hCG]) pregnancy test at screening and 24h prior to the start of study treatment and must agree to further urine or serum pregnancy tests during the study and within 6 months after receiving the last dose of study treatment\n- A woman must be: a. Not of childbearing potential, or b. Of childbearing potential and i. Practicing true abstinence; or ii. Have a sole partner who is vasectomized; or iii. Practicing 2 methods of contraception (at least 1 highly‑effective)\n- A female patient must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment\n- A male patient must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 3 months after receiving the last dose of study treatment. Male participants must also be advised of the benefit for a female partner to use a highly effective method of contraception as condoms may break or leak.\n- A male patients must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 3 months after receiving the last dose of study treatment.\n- Patient must be willing and able to adhere to the lifestyle restrictions specified in the protocol (Section 4.3)\n- All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events [NCI-CTCAE], Version 5.0 must be ≤ Grade 1 at the time of enrolment except for alopecia.\n- Patient has given voluntary written informed consent before performance of any study-related procedure nor part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care."}

Exclusion criteria

• {"criterion_text":"- Prior or current systemic therapy or SCT for any plasma cell dyscrasia, with the exception of 1 cycle of antimyeloma treatment or the emergency use of a short course of corticosteroids before treatment while waiting for results of genetic analysis\n- Patient has CNS or exhibits clinical signs of meningeal involvement of MM\n- Patient is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment\n- Patient plans to father a child while enrolled in this study or within 3 months after the last dose of study treatment\n- Patient is simultaneously enrolled in other interventional CT\n- Patient has received prior radiotherapy within 2 weeks of start of study therapy. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy ) to non CNS disease\n- Prior or concurrent exposure to any of the following: -Investigational vaccine other than SARS CoV-2 vaccine approved/ in use under emergency approval within 4 weeks -Live, attenuated vaccine within 4 weeks, before enrollment.Non-life vaccines authorized for emergency use (eg. COVID-19) and allowed (APPENDIX 22). - Monoclonal antibody therapy within 21 days (not use for the treatment of MM)\n- Received a strong CYP3A4 inducer within 5 half-lives prior to starting study treatment\n- A maximum cumulative dose of corticosteroids of ≥ 140 mg of prednisone or equivalent within 14 day period before the first dose of Tec-Dara or Tal-Dara\n- Allergy, hypersensitivity, or intolerance to boron or mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients, or sensitivity to mammalian-derived products or lenalidomide\n- Presence of the following cardiac conditions: a) New York Heart Association stage III or IV congestive heart failure (APPENDIX 19) b) Myocardial infarction or coronary artery bypass graft ≤ 6 months prior to starting study treatment c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d) Uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities.\n- Plasmapheresis within 28 days of starting study treatment defined as C1D1 of D-VRD.\n- Stroke, transient ischemic attack or seizure within 6 months prior to signing ICF\n- Any of the following: -Hepatitis B infection (ie, HBsAg or HBV-DNA +). In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status -Active hepatitis C infection as measured by + HCV-RNA testing. Patients with a history of HCV antibody + must undergo HCV-RNA testing. If a patient with history of chronic hepatitis C infection (HCV antibody and HCV-RNA positive) 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\n- 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\n- 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\n- Moderate or severe persistent asthma within the past 24 months, or uncontrolled asthma of any classification\n- Patient has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to other molecular antibodies.\n- Major surgery or significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or 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\n- Peripheral neuropathy or neuropathic pain Grade ≥ 2\n- Patient has a diagnosis of primary light chain amyloidosis, MGUS, SMM, plasma cell leukemia or active POEMS syndrome at the time of screening.\n- Myelodysplastic syndrome or active malignancies (progressing or requiring treatment change in the last 24 months) other than relapsed/refractory MM. Exceptions: malignancies treated within the last 24 months that are considered completely cured: -Non-muscle invasive bladder cancer -Skin cancer: non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone -Noninvasive cervical cancer -Localized prostate cancer, Gleason score of ≤ 7a, treated locally only -Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, localized breast cancer and receiving antihormonal agents -Other malignancy that is considered cured with minimal risk of recurrence"}

Primary endpoints

• {"endpoint_text":"- MRD measured by NGF (sensitivity level of 10-6) and FDG PET-CT scan using the Deauville score and CR evaluated per IMWG 2016 response criteria after 6 cycles of Tec-Dara therapy","definition_or_measurement_approach":"MRD measured by NGF (sensitivity level of 10-6); FDG PET-CT scan using the Deauville score; CR evaluated per IMWG 2016 response criteria after 6 cycles of Tec-Dara therapy."}

Secondary endpoints

• {"endpoint_text":"- MRD measured by NGF (sensitivity level of 10-6) and FDG PET-CT scan using the Deauville score and CR evaluated per IMWG 2016 response criteria after 4 cycles of D-VRD induction\n- MRD negative rates measured by NGS, and QIP-MS-FLC after 6 cycles of Tec-Dara therapy\n- Percentage of patients converting from positive MRD to negative MRD evaluated by NGF, NGS, QIP-MS-FLC and FDG-PET-CT scan.\n- Percentage of patients converting from positive MRD after D-VRD induction to negative MRD evaluated by NGF, NGS, QIP-MS-FLC and FDG-PET-CT scan after Tec-Dara intensification.\n- Proportion of patients with persistent MRD negative disease at month 6, 12, 18 and 24 of maintenance treatment in both Tec-Dara and Tal-Dara treatment, by NGF, NGS, QIP-MS-FLC and FDG-PET-CT scan and annually thereafter\n- Proportion of patients relapsing from MRD negative CR to MRD positive or who relapse from CR (not fulfilling criteria for disease progression) during any phase of Tec-Dara treatment (intensification or maintenance)\n- PFS, EFS, TNT, DoR and OS\n- Incidence of treatment-emergent adverse events\n- Analysis of immune subpopulation and genetic markers.","definition_or_measurement_approach":"Endpoints include MRD assessment by NGF (sensitivity 10-6), NGS, QIP-MS-FLC and imaging (FDG PET-CT with Deauville score); clinical response by IMWG 2016 criteria after specified cycles; time-to-event endpoints (PFS, EFS, TNT, DoR, OS) and safety assessed by incidence of treatment-emergent adverse events; immune profiling and genetic marker analysis as described."}

Spain

Earliest CTIS Part Ii Submission Date

31-07-2024

Latest Decision Or Authorization Date

07-05-2025

Processing Time Days

280

Number Of Sites

11

Number Of Participants

30

Primary sponsor

Full Name

Fundacion Pethema

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Contract research organisations

Name

Evidenze Health Espana S.L.

Responsibilities

codes: 1, 15 (Regulatory), 6, 8

Name

Clinigen Clinical Supplies Management

Responsibilities

code: 14

Third parties

• {"country":"Spain","full_name":"Evidenze Health Espana S.L.","duties_or_roles":"codes: 1, 15 (Regulatory), 6, 8","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}