Multiple myeloma is a type of blood cancer that can come back even after effective treatment. After high-dose therapy and autologous stem cell transplantation (ASCT), some patients have no visible signs of disease, but small numbers of cancer cells may still remain in the body. This is called measurable residual disease (MRD). These remaining cells may lead to disease relapse.
The purpose of this study is to find out whether a new maintenance treatment can eliminate these remaining cancer cells more effectively than the current standard treatment. More effective maintenance therapy may help reduce the risk of disease progression and improve long-term outcomes for patients.
This study, called TiTan, is a phase III, multicenter clinical trial conducted in Poland. It will include 248 adult patients with newly diagnosed multiple myeloma who have undergone ASCT, have no signs of disease progression, but still have detectable MRD.
Participants will be randomly assigned (by chance) to one of two treatment groups. Neither the patient nor the doctor can choose the group.
In the experimental group, patients will receive two immunotherapy medicines, teclistamab and talquetamab. If MRD becomes undetectable after the protocol-defined period, treatment may be stopped and the patient will continue under observation.
In the standard treatment group, patients will receive daratumumab and lenalidomide, which are commonly used maintenance treatments. The duration and adjustments of treatment may depend on MRD results.
The main goal of the study is to determine how many patients achieve undetectable MRD after 12 months of treatment together with a complete response to therapy. This will show whether the new treatment is more effective in removing residual cancer cells.
The study will also evaluate how long patients live without disease progression, overall survival, treatment safety, and the impact of treatment on patients' daily functioning and quality of life. In addition, researchers will assess whether achieving undetectable MRD leads to better long-term outcomes.
Patient safety will be closely monitored throughout the study. Participants will undergo regular medical check-ups, including blood tests, bone marrow tests, and imaging studies. All side effects will be carefully recorded and assessed according to international standards. Patients may withdraw from the study at any time without giving a reason.
This non-commercial study aims to improve knowledge about maintenance treatment in multiple myeloma after ASCT and may help support future treatment decisions for patients with this disease.
Inclusion Criteria:
Exclusion Criteria:
Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the NCI CTCAE Version 5.0.
COPD with a FEV1 <50% of predicted normal. Note that FEV1 testing is required for participants with known or suspected of having COPD or asthma and participants must be excluded if FEV1 <50% of predicted normal.
Severe persistent asthma within the past 2 years (see Appendix x[DS2.1] [for severity of Asthma]), uncontrolled asthma of any classification. Note that FEV1 testing is required for participants known or suspected asthma and participants must be excluded if FEV1 <50% of predicted normal.
CNS involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.
Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary light chain amyloidosis.
Any ongoing myelodysplastic syndrome or B cell malignancy (other than multiple myeloma).
Any history of malignancy, other than multiple myeloma, which is considered at high risk of recurrence requiring systemic therapy.
Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than multiple myeloma. The only allowed exceptions are malignancies treated within the last 24 months that are considered cured:
Stroke, transient ischemic attack, or seizure within 6 months prior to signing ICF.
Presence of the following cardiac conditions:
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, such as:
Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug (daratumumab, lenalidomide, teclistamab or talquetamab) or its excipients (refer to the appropriate IBs and SmPCs) or analogues and study-required co-medication.
Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs.
Received a strong CYP3A4 inducer within 5 half-lives prior to the first dose of study treatment (Flockhart 2021).
Plasmapheresis within 28 days prior to the first dose of study treatment.
Participant 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 participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment.
NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery. If there is a question whether a procedure is considered a major surgery, the investigator must consult with the appropriate Sponsor representative and resolve any issues before enrolling a participant in the study.
Taken any disallowed therapies as noted in Section 6.8, Concomitant Therapy before the planned first dose of study treatment.
Received a live, attenuated vaccine within 4 weeks before the first dose of study drug. Non-live or replicating vaccines approved or authorized for emergency use (eg, COVID-19) by local health authorities are allowed.
HIV infection (positive, history, treatment for HIV).
Hepatitis B infection (ie, HbsAg or HBV-DNA positive). 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 positive HCV-RNA testing. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the completion of therapy, the participant is eligible for the study.
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Participants receive maintenance therapy with teclistamab in combination with talquetamab. The study evaluates whether maintenance treatment with dual immunotherapy can improve eradication of measurable residual disease in participants with newly diagnosed multiple myeloma who remain MRD-positive after autologous stem cell transplantation. Treatment is administered according to protocol-defined procedures, and participants are followed for assessment of efficacy and safety outcomes.
Participants receive maintenance therapy with daratumumab and lenalidomide. This treatment regimen represents the comparator maintenance strategy for participants with newly diagnosed multiple myeloma who remain MRD-positive after autologous stem cell transplantation. Treatment is administered according to protocol-defined procedures, and participants are followed for assessment of efficacy and safety outcomes.
A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal-DR) in Participants With Newly Diagnosed Multiple Myeloma
Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation
GMMG-HD10 / DSMM-XX / 64007957MMY2003, MajesTEC-5
A Study of Different Sequences of Cilta-cel, Talquetamab in Combination With Daratumumab and Teclistamab in Combination With Daratumumab Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in Participants With Standard-risk Newly Diagnosed Multiple Myeloma
Bispecific T-cell Redirectors as Part of First Line Treatment in Transplant Eligible Multiple Myeloma Patients
Teclistamab-Daratumumab and Talquestamab-Daratumumab in Newly Diagnosed High-risk Multiple Myeloma
A Phase II Study to Evaluate the Efficacy and Safety of Teclistamab in Combination With Daratumumab (Tec-Dara) in Newly Diagnosed Multiple Myeloma With Concurrent Light Chain Amyloidosis (MM+AL).
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