Phase 3 study with Teclistamab in combination with Lenalidomide compared to Lenalidomide alone in participants with newly diagnosed bone marrow cancer (multiple myeloma) as maintenance therapy after autologous stem cell transplantation.
Résumé de l'étude
This study aims to further improve treatment options for the cancer arising from bone marrow plasma cells. The so-called multiple myeloma is caused by the growth of abnormal plasma cells in the bone marrow. It will primarily investigate how well the addition of Teclistamab to the standard treatment of Lenalidomide works. For comparison, one trial group will be treated with Teclistamab and Lenalidomide, and another group will be treated only with Lenalidomide. Since existing therapies usually delay the course of the disease, the standard treatment is also referred to as maintenance therapy. The maintenance therapy follows an autologous stem cell transplantation. Teclistamab is a body defense substance (antibody) that can bind to malignant cells of multiple myeloma and kill them. The planned study will be conducted at multiple sites in various countries. A total of approximately 1020 patients will participate in the study worldwide. The study is organized by the European Myeloma Network (EMN) and funded by the company Janssen. The study will last a total of 10 years (2 years of treatment and 8 years of long-term observations). Data will be continuously collected from the treated patients. Patients will be randomly assigned to one of the two treatment groups. Both patients and investigators are aware of which treatment is being administered. Patients will be invited to a series of examinations such as bone marrow and blood tests. No patients will be allowed in this study who have, for example, received a previous BCMA-directed therapy (BCMA means B-cell maturation antigen, a protein on the cell surface), received radiation therapy within 14 days prior to this study, have a history of allogeneic stem cell transplantation, or have myelodysplastic syndrome.
(BASEC)
Intervention étudiée
We want to further improve the treatment of multiple myeloma. There are a number of different treatment options for multiple myeloma. Unfortunately, the disease almost always returns, even after a very good response to treatment, so multiple myeloma must currently be considered an incurable disease.
This study will primarily investigate how well the addition of Teclistamab to the standard maintenance therapy with Lenalidomide works compared to the standard treatment with Lenalidomide alone.
Teclistamab (also known as JNJ-64007957) is a humanized bispecific antibody that binds to a specific receptor complex on T-cells and a specific protein (BCMA, which means B-cell maturation antigen) on plasma cells. With its two binding sites, Teclistamab can attract specific T-cells close to myeloma cells. This activates the T-cells, which can then find and destroy the myeloma cells.
The duration of the study is about 10 years. The duration of treatment will be about 2 years. The exact duration depends on how the disease responds to the treatment. After the treatment is completed, patients will be observed for about 8 years.
Before participants can take part in the study, they must complete several tests. These tests include a physical examination (including neurological examination), measurements of weight, height, blood pressure, heart rate, respiratory rate, oxygen saturation, and temperature, an electrocardiogram (ECG), a chest X-ray or low-dose chest CT scan, a pregnancy test (if applicable), bone marrow tests, blood tests for safety laboratory tests, multiple myeloma cells, and biomarkers, as well as 24-hour urine tests.
This phase 3 study will be conducted in several hospitals in multiple countries worldwide. Participants will be selected from those with newly diagnosed multiple myeloma who have completed induction therapy followed by autologous stem cell transplantation with or without consolidation. Participants will be randomly assigned to the new treatment or the control group. Randomization will occur in 3 phases: screening (up to 28 days), treatment, and follow-up.
There will be two different treatment groups in this study. It is important that the groups receiving the respective treatment are as similar as possible at the start of the study. To ensure this, participants will be randomly assigned to the individual groups. Each study participant will be assigned to one of the two groups. The groups will be selected by a computer that has no information about the person, i.e., randomly, like flipping a coin. The subjects in each group will then receive a different treatment and will be compared with each other. The drugs in this study will be allocated in a 1:1 ratio, so that participants have a 50% chance of receiving one of the two study treatments. Approximately 1000 additional participants will also be distributed in a 1:1 ratio to both groups. Randomization will be based on individual medical history and disease progression.
However, before randomization begins, there will be a safety portion of the study where about the first 20 patients in the study will receive Lenalidomide and Teclistamab according to the same scheme as in Arm A (TecLen) of the randomized part of the study. A committee will review the safety data from at least the first two treatment cycles, and as long as no safety issues (side effects) are identified, the randomized part of the study will begin, where the remaining eligible patients will be admitted to randomization into one of the two treatment groups.
Patients will receive the study treatment continuously over a period of 2 years or until confirmed disease progression, until death, until the occurrence of intolerable toxic side effects, or until withdrawal of consent, whichever occurs first.
After the completion of maintenance therapy, laboratory tests will be performed every 8 weeks to obtain information about the patient's myeloma response.
After disease progression, information about the patient's condition, new treatments received for multiple myeloma, response to these treatments, questionnaires, development of new cancers, and survival will be collected every 4 months. This information can be obtained during regular doctor visits or through phone contacts every 4 months, with no additional visits required for the study.
After the end of study participation, the study doctor may also access public records if necessary to collect information on survival, as permitted by local regulations.
Bone marrow, blood, and urine samples will be taken for the study and must be repeated. Other tests/procedures are part of standard treatment but may sometimes need to be repeated for the study. Blood samples will be taken to determine the concentrations of Teclistamab in the body over time. If for any reason a tissue sample (biopsy) is performed, a sample should be sent to the central laboratory.
At 7 time points and at specific evaluation points, additional samples for biomarkers will be taken. Biomarkers are substances that provide information about the effectiveness of treatment.
At 9 time points during the study and additionally in cases where clinically indicated, blood will be drawn to determine the concentration of Teclistamab in the patient's body. This type of examination is called pharmacokinetics (PK) and will be performed only in Arm A (TecLen).
Peripheral blood and bone marrow samples will be taken from participants in both treatment groups. The evaluation will focus on the following objectives: 1) evaluation of biomarkers indicating the mechanism of action of Teclistamab and Lenalidomide; 2) determination of the ability of the study treatment to induce and maintain the negativity of minimal residual disease; 3) investigation of biomarkers for response or resistance in both peripheral blood and bone marrow.
It is important to know whether the treatment improves the quality of life of patients. For this reason, patients will be asked to complete four questionnaires every three months during treatment and every four months thereafter. These four questionnaires consist of simple questions, where patients can usually choose from 4 options. Completing the questionnaires takes about 30 to 45 minutes in total. Patients will also be asked to fill out a questionnaire about symptoms and side effects of the treatment every week during the first six treatment cycles.
(BASEC)
Maladie en cours d'investigation
Multiple myeloma is a cancer that affects a type of white blood cell called plasma cells. It is characterized by bone damage, increased susceptibility to infections, elevated calcium levels in the blood, anemia (a condition in which red blood cells are unable to provide sufficient oxygen to body tissues), and kidney failure. Each year, the disease is diagnosed in about 130,000 patients worldwide, and the number of patients has increased over the past 20 years in all parts of the world. It accounts for about 10% of all cancers affecting the blood and blood-forming organs. In patients with multiple myeloma, plasma cells produce antibodies (proteins that the immune system uses to recognize and neutralize, for example, bacteria and viruses) that have lost their function. These abnormal antibodies are called M-proteins, and their overproduction causes the characteristic symptoms of the disease. Treatment options for multiple myeloma have improved significantly over time and depend on the aggressiveness of the disease, underlying prognostic factors (characteristics of a patient that can help estimate the chances of cure), the physical condition of the patient, and the presence of other diseases. These options include, for example, drugs that block proteasomes (cellular complexes that break down proteins), immunomodulatory drugs (drugs that regulate immune responses), or monoclonal antibodies (antibodies derived from white blood cells that target only one objective). Despite the development of such drugs or antibodies that have significantly improved patient outcomes, the disease still cannot be cured and will recur over the patient's lifetime. With each recurrence of the disease, the chances of responding to treatment decrease and may eventually approach zero. Therefore, many efforts have focused on improving the initial treatment, as this offers the highest likelihood of a long disease-free interval. In younger, fit patients, treatment with high doses of the drug Melphalan in combination with stem cell transplantation (blood-forming cells) remains an important treatment strategy that has been shown to improve the duration during and after treatment in which the patient lives without the disease worsening. With increasing tolerability of new drugs, treatment approaches aimed at preventing cancer from reappearing after the initial therapy has disappeared (so-called maintenance therapy) have allowed patients to achieve extended disease control and better outcomes after stem cell transplantation. Compared to placebo (control treatment with an inactive substance), maintenance therapy with the drug Lenalidomide after such a stem cell transplantation has been shown to improve the duration during which the disease does not relapse and to extend the overall survival of patients. Therefore, this treatment is now considered the standard treatment for all patients. However, the symptoms of the disease return in most patients even with this treatment. In particular, in older patients, for whom stem cell transplantation is often not an option, and in patients who have exhausted all available therapies, multiple myeloma remains an incurable cancer and an unmet medical need with high complication and mortality rates. This opens the possibility of introducing new drugs for maintenance therapy that could further improve the duration of the absence of disease damage and overall survival.
(BASEC)
Each potential participant must meet all of the following criteria to be included in the study: 1. ≥18 years old 2. Have a recent diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) criteria and have received 4 to 6 cycles of initial therapy with 3 or 4 drugs containing a proteasome inhibitor and/or an immunomodulatory drug (IMiD ) with or without anti-CD38 monoclonal antibody and single or tandem autologous stem cell transplantation (ASCT). Post-ASCT treatment is allowed for up to 2 cycles as long as the total number of cycles does not exceed 6 and all pre-screening treatment is completed. 3. You must have received only one line of therapy and have achieved at least a partial response (≥PR) according to the 2016 IMWG Response Criteria. Participants with a plasma cell tumor (plasmocytoma) at the time of diagnosis must complete the IMWG Meet 2016 response criteria for ≥PR based on re-imaging during screening using the same modality. 4. There must be no intolerance to the starting dose of lenalidomide.) 5. Must have received high-dose chemotherapy and ASCT within 12 months of starting initial therapy and be within 6 months of last ASCT at time of initial treatment dose. a) For participants who have not received consolidation therapy (which is administered after the cancer has resolved after the initial therapy), the participant must be within 120 days of transplantation at the time of the first treatment dose. b) For participants treated with consolidation therapy, the last dose of consolidation therapy must be less than 90 days at the time of the first treatment dose. 6. The participant must not receive maintenance therapy (which serves to prevent the cancer from coming back after it has gone after initial therapy). 7. An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening and immediately prior to study treatment initiation. 8. Clinical laboratory values that meet certain criteria during the screening phase. In addition, these laboratory values must be taken again within 72 hours before the first dose and the participant must also meet all criteria. If one or more criteria are not met within 72 hours prior to administration, a repeat laboratory test is allowed. If more than one repeat laboratory test is required, the sponsor must be consulted prior to administration. 9. A woman of childbearing potential must have a negative high-sensitivity serum pregnancy test within 10-14 days prior to the start of study treatment and within Re-take either a serum or urine pregnancy test within 24 hours of the start of study treatment and must consent to further serum or urine pregnancy tests during the study. 10. A woman must be: a) Not of childbearing age, or b) be of childbearing age and 1) practice real abstinence; or 2) Use 2 reliable contraceptive methods concurrently, including one highly effective method of contraception and one other effective method of contraception, from 4 weeks prior to dosing, throughout the study, including dose interruptions, and for at least 4 weeks after the last lenalidomide dose, or for at least 90 Days after the last Teclistamab dose, whichever is later. In participants who are of childbearing potential, concomitant use of estrogen-containing products and lenalidomide may increase the risk of thrombosis. If use of this combination is required, these drugs should be used with caution and the participant should be monitored for possible thromboembolic events. NOTE: If a woman becomes of childbearing potential after the start of the study, she must comply with point (b) as described above. NOTE: Sexual abstinence is considered a highly effective method only when defined as abstaining from heterosexual intercourse throughout the range of risk associated with the study treatment. The reliability of sexual abstinence needs to be assessed depending on the duration of the study and the participant's preferred and usual lifestyle. 11. A woman must agree not to receive oocytes (oocytes) during the study and for at least 4 weeks after the last dose of lenalidomide or for at least 90 days after the last dose of Teclistamab, whichever is later. to donate or freeze for future use to facilitate artificial insemination. 12. The male must wear a condom (with spermicidal foam/gel/film/cream/suppository) if during the study and at least four weeks after the last dose of lenalidomide, or at least 90 days after the last dose of Teclistamab, as appropriate , whichever is later, engages in an activity where ejaculate may be given to another person. If his partner is of childbearing potential, she must also be using a highly effective method of contraception. NOTE: If the male participant is vasectomized, he must continue to wear a condom (with spermicidal foam/gel/film/cream/suppository), but his partner is not required to use contraception. 13. A male participant must agree to be available during the study and for at least 4 weeks after the last dose of lenalidomide or for at least 90 days after Teclistamab, whichever is later, not to donate sperm for reproductive purposes. 14. You must be willing and able to comply with the lifestyle restrictions specified in the study protocol. 15. The participant (or their legal representative) to sign an Informed Informed Consent Form (ICF) confirming that they understand the purpose of the study and the procedures required to achieve it, and that they are willing to participate in the study. (BASEC)
Critères d'exclusion
1. You have already received B cell maturation antigen (BCMA) targeted therapy. 2. Any prior therapy with an immune cell redirecting agent or genetically engineered adoptive cell therapy 3. Discontinuation of treatment due to lenalidomide-related adverse events, as determined by the investigator. 4. History of allogeneic stem cell transplantation or previous organ transplantation requiring immunosuppressive therapy. 5. Progression of multiple myeloma therapy according to the 2016 IMWG response criteria prior to screening. 6. Radiation therapy within 14 days or focal irradiation within 7 days after the first treatment dose. 7. Receiving a cumulative dose of corticosteroids equivalent to ≥140 mg prednisone within the 14 days prior to the first treatment dose. 8. You have received a live attenuated vaccine within 4 weeks prior to the first dose of treatment. For emergency approved non-live vaccines (e.g. COVID-19) are allowed. 9. Myelodysplastic syndrome or active malignancy (i.e. disease progression or need for a treatment switch within the last 24 months). The only allowed exceptions are: a) Non-muscle invasive bladder cancer (treated within the last 24 months and considered fully cured) b) Skin cancer (non-melanoma or melanoma) (treated within the last 24 months and considered fully cured) c) Non-invasive cervical cancer (treated within the last 24 months and considered fully cured) d) Localized prostate cancer (N0M0): 1) With a Gleason score ≤6, treated/untreated within the last 24 months and under surveillance 2) With a Gleason score of 3+4, treated >6 months prior to full screening in the study and at very low risk of recurrence, or 3) with a localized prostate carcinoma a history of being treated with androgen deprivation therapy and who are at very low risk of disease recurrence. e) Breast cancer: Adequately treated lobular carcinoma in situ or ductal carcinoma in situ or history of localized breast cancer treated with anti-hormonal agents and for which the risk of recurrence is estimated to be very low f) Other malignancies considered cured and where the risk of recurrence is minimal. 10. Plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) or primary light chain amyloidosis. 11. Central nervous system involvement or clinical evidence of meningeal involvement of multiple myeloma. If multiple myeloma is suspected, a magnetic resonance imaging of the brain (MRI) and a Lumbar cytology required. 12. Stroke or seizure within 6 months of the first treatment dose. 13. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study treatment Treatment or its excipients (see investigator information and latest valid RSI). 14. The participant is pregnant or breastfeeding, or plans to become pregnant while participating in this study or within 90 days of the last dose of study drug. 15. The participant plans to father a child while participating in this study or within 90 days of the last Dose of study drug. 16. Presence of the following cardiac conditions: a) New York Heart Association stage III or IV congestive heart failure b) Myocardial infarction or coronary bypass surgery ≤6 months prior to initial treatment dose c) Clinically significant ventricular arrhythmia in the History or unexplained syncope that is not that are not considered vasovagal or due to dehydration d) Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) anomalies. 17. HIV-positive participants with one or more of the following: - History of Acquired Immune Deficiency Syndrome (AIDS) - defining conditions - CD4 count <350 at screening - Detectable viral load at screening or within the last 6 months prior to screening (see - Table 2) - Not on highly active antiretroviral therapy (ART) - Switched antiretroviral therapy within 6 months of starting screening - You are receiving antiretroviral therapy which may interfere with treatment in the study, as determined following consultation with the Medical Monitor. 18. Hepatitis B infection (i.e., HBsAg or HBV DNA positive): If infection status is unclear, viral counts are quantitative required to determine infection status according to the protocol. 19. Active hepatitis C infection as measured by a positive hepatitis C virus (HCV) ribonucleic acid (RNA) test. Participants with a history of HCV antibody positivity must undergo HCVRNA testing. If a participant with a history of chronic HCV infection (defined as being both HCV antibody and HCV RNA positive) has completed antiviral therapy and has undetectable HCVRNA 12 weeks after stopping therapy, the participant is eligible for approved the study. 20. Concomitant medical or psychiatric conditions or illnesses that are likely to interfere with the study procedures or results or that the investigator considers to pose a risk to participation in this study, e.g. e.g.: a) Uncontrolled diabetes b) Peripheral neuropathy grade 3 or higher c) Acute diffuse infiltrative lung disease d) Evidence of active systemic viral, fungal or bacterial infection causing a systemic antimicrobial therapy e) History of an autoimmune disease with the exception of: i. Vitiligo that is not treated systemically ii. type I diabetes iii. previous autoimmune thyroiditis, currently based on clinical symptoms and laboratory tests f) Disabling psychiatric illness (e.g. alcohol or drug abuse), severe dementia or altered mental status g) Any other problem that would affect the participant's ability to receive or tolerate the planned treatment at the study site receiving or tolerating the proposed treatment at the trial site, understanding informed consent, or a condition where, in the investigator's opinion, participation is not in the participant's interest (e.g., participant's interest (e.g., impairment of well-being) or the test plan prevent, limit or frustrate the investigations provided for in the investigation plan h) Failure to comply with recommended medical treatments in the past 21. Major surgery within 2 weeks prior to study treatment initiation. Or the participant has not fully recovered from prior surgery or is planning major surgery during the time the participant is expected to participate in the study or within 2 weeks of the last dose of study treatment. NOTE: Participants with planned surgical procedures to be performed under local anesthesia may participate. Vertebral augmentations are not considered major surgical procedures. If there is a question as to whether a procedure qualifies as a major surgical procedure, the investigator must consult the sponsor and clarify any questions before admitting a participant to the study (BASEC)
Lieu de l’étude
Bâle, Berne, St-Gall
(BASEC)
Sponsor
Sponsor: European Myeloma Network – EMN Legal representative: GCP-Service International Ltd. & Co. KG
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Sarah Lonergan
0031 10 703 3740
secretariaat.psonneveld@cluttererasmusmc.nlEuropean Myeloma Network – EMN
(BASEC)
Informations générales
European Myeloma Network - EMN
0031107033740
secretariaat.psonneveld@cluttererasmusmc.nl(ICTRP)
Informations scientifiques
European Myeloma Network - EMN
0031107033740
secretariaat.psonneveld@cluttererasmusmc.nl(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Ethikkommission Ostschweiz EKOS
(BASEC)
Date d'approbation du comité d'éthique
11.08.2022
(BASEC)
Identifiant de l'essai ICTRP
EUCTR2021-002531-27 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
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 – MajesTEC4 (BASEC)
Titre académique
Phase 3 Study of Teclistamab in Combination with Lenalidomide versus Lenalidomide Alone in Participants with Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation - MajesTEC-4 (ICTRP)
Titre public
Phase 3 Study of Teclistamab in Combination with Lenalidomide versus Lenalidomide Alone in Participants with Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation (ICTRP)
Maladie en cours d'investigation
Newly Diagnosed Multiple Myeloma
MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)
Intervention étudiée
Product Name: Teclistamab 90mg/ml
Product Code: JNJ-64007957
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Teclistamab
CAS Number: 2119595-80-9
Current Sponsor code: JNJ-64007957-AAA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 90-
Product Name: Teclistamab 10mg/ml
Product Code: JNJ-64007957
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Teclistamab
CAS Number: 2119595-80-9
Current Sponsor code: JNJ-64007957-AAA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Product Name: Lenalidomide 2.5mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lenalidomide
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Product Name: Lenalidomide 5mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lenalidomide
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Product Name: Lenalidomide 10mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lenalidomide
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Product Name: Lenalidomide 15mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lenalidomide
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
(ICTRP)
Type d'essai
Interventional clinical trial of medicinal product (ICTRP)
Plan de l'étude
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2 (ICTRP)
Critères d'inclusion/exclusion
Gender:
Female: yes
Male: yes
Inclusion criteria:
1 =18 years of age
2 Must have a new diagnosis of MM according to IMWG criteria and have received 4 to 6 cycles of 3 or 4 drug-induction therapy that includes a proteasome inhibitor and/or an IMiD with or without anti-CD38 monoclonal antibody and a single or tandem ASCT. Post ASCT consolidation is permitted for up to 2 cycles as long as the total number of induction plus consolidation cycles does not exceed 6 and all treatment has completed prior to screening.
3 Must have received only one line of therapy and achieved at least a partial response (=PR) as per IMWG 2016 response criteria. Participants with plasmacytomas at the time of diagnosis must meet IMWG 2016 response criteria for =PR based on repeat imaging during screening utilizing the same modality.
4 Must not be intolerant to the starting dose of lenalidomide.
5 Must have received high-dose chemotherapy and ASCT within 12 months of the start of induction therapy and be within 6 months of the last ASCT at the time of first treatment dose. a) For participants who have not received consolidation therapy, the participant must be within 120 days post-transplant at the time of first treatment dose. b)For participants treated with consolidation therapy, the participant must be within 90 days of the last dose of consolidation therapy at the time of first treatment dose
6 Must not have received any maintenance therapy.
7 Have an ECOG performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment.
8 Have clinical laboratory values meeting the following criteria during the Screening Phase. In addition, these laboratory values must be re-evaluated within 72 hours prior to the first dose and the participant must also meet all criteria. If one or more criteria are not met within 72 hours prior to dosing, one repeat of laboratory testing is permitted. If >1 repeat laboratory test is necessary, the sponsor must be consulted prior to dosing.
9 A woman of childbearing potential must have a negative highly sensitive serum pregnancy test within 10-14 days prior to the start of study treatment and again either a serum or urine pregnancy test within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
10 A woman must be: a) Not of childbearing potential, or b) Of childbearing potential and 1) Practicing true abstinence; or 2) Practicing 2 reliable methods of contraception simultaneously including one highly effective method of contraception and one other effective method of contraception starting 4 weeks prior to dosing, throughout the study including during dose interruptions and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of 90 days after the last dose of teclistamab, whichever occurs later. For participants who are of childbearing potential, see Section 6.11.3 for details regarding concomitant use of estrogen containing products and lenalidomide.
11 A woman must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for a minimum of 4 weeks after the last dose of lenalidomide or for a minimum of 90 days after the last dose of teclistamab, whichever occurs later.
12 A man must wear a condom (with spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 4 (ICTRP)
Exclusion criteria:
1 Received any prior BCMA-directed therapy.
2 Any previous therapy with an immune cell redirecting agent or gene modified adoptive cell therapy.
3 Discontinued treatment due to any AE related to lenalidomide as determined by the investigator.
4 History of allogeneic stem cell transplantation or prior organ transplant requiring immunosuppressive therapy.
5 Progressed on multiple myeloma therapy as per IMWG 2016 response criteria at any time prior to screening.
6 Radiotherapy within 14 days or focal radiation within 7 days of first treatment dose.
7 Received a cumulative dose of corticosteroids equivalent to =140 mg of prednisone within the 14 days prior to first treatment dose.
8 Received a live, attenuated vaccine within 4 weeks before first treatment dose. Non-live vaccines authorized for emergency use are allowed.
9 Myelodysplastic syndrome or active malignancies. The only allowed exceptions are: a)Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured b)Skin cancer treated within the last 24 months that is considered completely cured c) Noninvasive cervical cancer treated within the last 24 months that is considered completely cured d)Localized prostate cancer: 1) With a Gleason score of =6, treated within the last 24 months or untreated and under surveillance 2)With a Gleason score of 3+4 that has been treated >6 months prior to full study screening and considered to have a very low risk of recurrence or 3)History of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence. e)Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence f)Other malignancy that is considered cured with minimal risk of recurrence.
10 Plasma cell leukemia, Waldenstr?m?s macroglobulinemia, POEMS syndrome or primary light chain amyloidosis.
11 Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain MRI and lumbar cytology are required.
12 Stroke or seizure within 6 months of first treatment dose.
13 Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study treatment or its excipients .
14 Participant is pregnant or breast-feeding or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study drug.
15 Participant plans to father a child while enrolled in this study or within 90 days after the last dose of study drug.
16 Presence of the following conditions: a)New York Heart Association stage III or IV congestive heart failure b)Myocardial infarction, or coronary artery bypass graft =6 months prior to first treatment dose 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 electrocardiogram (ECG) abnormalities.
17 HIV -positive participants with 1 or more of the following: -History of AIDS defining conditions -CD4 count <350 at screening -Detectable viral load during screening or within 6 months prior to screening -Not receiving highly ART -Had a change in antiretroviral therapy within 6 months of the start of screening -Receiving antiretroviral therapy that may interfere wit
Critères d'évaluation principaux et secondaires
Main Objective: To compare the efficacy of teclistamab in combination with lenalidomide (Tec-Len; Arm A) with that of lenalidomide (Len; Arm B) as assessed by PFS.
;Secondary Objective: To further compare the efficacy of Tec Len maintenance compared with Len.
To assess the safety profile of Tec Len, characterize the PK of Tec Len, assess the immunogenicity of Tec Len, evaluate the impact of treatment with Tec Len on PROs compared with Len.
EXPLORATORY OBJECTIVES:
To evaluate the efficacy of Tec-Len in high-risk subgroups, explore pharmacodynamic biomarkers of antimyeloma and immune activity for Tec-Len, explore relationships between pharmacodynamic markers and clinical activity of Tec Len compared with Len, explore predictive biomarkers of response and resistance for Tec Len.
To evaluate MRD negative conversion and CR or better conversion.
To explore the relationships between PK, pharmacodynamic, AE profile, and clinical activity of Tec-Len.
To explore time to symptomatic progression in both treatment arms.
To explore the impact of treatment with Tec-Len on MRU compared with Len.;Primary end point(s): The primary endpoint is PFS, defined as the time from the date of randomization to the date of first confirmed disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.
;Timepoint(s) of evaluation of this end point: From the date of randomization to the date of first confirmed disease progression or death due to any cause, whichever occurs first.
(ICTRP)
Secondary end point(s): CR or better (sCR+CR) is defined as participants who achieve a CR or better response per IMWG criteria.
MRD negative CR is defined as participants who achieve CR or better and are MRD negative before initiation of subsequent therapy.
Sustained MRD negativity is defined as the proportion of participants who achieve MRD-negative CR, confirmed minimum 1 year apart and without any examination showing MRD-positive status in between.
OS will be measured from the date of randomization to the date of the participant?s death. If the participant is alive or the vital status is unknown, then the participant?s data will be censored at the date the participant was last known to be alive.
PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as PD as assessed by investigator on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first. Those who are alive and for whom a second
disease progression has not been observed will be censored at the last date of follow-up.
Incidence and severity of AEs
The PK of teclistamab will be assessed.
Presence and activity of ADAs to teclistamab
Time to worsening in overall HRQoL, symptoms, and functioning
Change from baseline in overall HRQoL, symptoms, and functioning
PFS, depth of response, etc will be determined in participants with high-risk molecular features as defined by IMWG criteria
As part of the PROs, treatment effect will be assessed by change from baseline in overall HRQoL symptoms and functioning at each time point summarized by treatment arm. Time to worsening of symptoms will be measured as the interval from the date of randomization to the start date of worsening. Death due to disease progression will be considered as worsening.
Participants who have not met the definition of worsening will be censored as of the last assessment date.
The analysis methods for binary endpoints (eg, CR/sCR, and MRD negativity) will be conducted using stratified Cochran Mantel Haenszel test. The Mantel Haenszel odds ratio will be provided along with its 2-sided 95% CI and will be provided as the measure of treatment
effect. For time-to-event endpoints (eg, PFS2, OS, and time of worsening symptoms), similar statistical methods will be applied as for PFS.
EXPLORATORY ENDOPOINTS:
To evaluate the efficacy of Tec-Len in high-risk subgroups
To explore pharmacodynamic biomarkers of antimyeloma and immune activity for Tec-Len
To explore relationships between pharmacodynamic markers and clinical activity of Tec-Len compared with Len
To explore predictive biomarkers of response and resistance for Tec-Len, including prognostic and disease markers, at baseline, during treatment, and in relation to efficacy parameters
To evaluate rate of conversion to CR and MRD negative CR
To explore the relationships between PK, pharmacodynamic, AE profile, and clinical activity of Tec-Len
To explore time to symptomatic progression in both treatment arms
To explore the impact of treatment with Tec-Len on MRU compared with Len
;Timepoint(s) of evaluation of this end point: During the entire duration of the study (ICTRP)
Date d'enregistrement
23.03.2022 (ICTRP)
Inclusion du premier participant
21.07.2022 (ICTRP)
Sponsors secondaires
non disponible
Contacts supplémentaires
Sarah Lonergan, secretariaat.psonneveld@erasmusmc.nl, 0031107033740, European Myeloma Network - EMN (ICTRP)
ID secondaires
EMN30/64007957MMY3003, 2021-002531-27-GR (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-002531-27 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible