IBERDOMIDE for Multiple myeloma | Newly diagnosed multiple myeloma

Inclusion criteria

• {"criterion_text":"-Participants with newly diagnosed MM, requiring therapy due to the presence of CRAB symptoms or myeloma defining events and measurable disease (sPEP ≥0.5 g/dL and/or uPEP ≥ 200 mg/24h and/or FLC involved ≥ 10 mg/dL with abnormal FLC ratio) before induction therapy with a PI and IMID-containing regimen\n-Male participants must: Practice true abstinence* (which must be reviewed on a monthly basis and source documented) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the trial, during dose interruptions and for at least 90 days following the last dose of trial treatment, even if he has undergone a successful vasectomy. *True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the participant. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.]\n-Males must agree to refrain from donating sperm while on trial treatment, during dose interruptions and for at least 90 days following last dose of trial treatment.\n-All participants must agree to refrain from donating blood while on study treatment, during dose interruptions and for at least 28 days following the last dose of trial treatment.\n-All male and female participants must follow all requirements defined in the Pregnancy Prevention Program (v5.1).\n-Participant agree to refrain from donating blood while on iberdomide, during dose interruption and for at least 28 days following the last iberdomide dose\n-Baseline values: -\tANC ≥1.0 x 10^9/L without use of growth factors; -\tPLTs≥75 x10^9/L (transfusions within 14 days from Day1 cycle 1 to achieve this cut off are not allowed); -\tHb >8 g/dL (transfusions within 14 days from Day1 cycle 1 to achieve this cut off are not allowed);\n-Life expectancy ≥ 3 months\n-Participants with complete baseline evaluation at the time of diagnosis according to revised International Staging System (R-ISS) (cytogenetic profile, ISS and LDH)\n-Participants treated with proteasome inhibitor plus immunomodulatory drug-based induction (3-6 cycles), followed by single or double autologous stem cell transplant (ASCT) with melphalan as condItioning regimen +/- consolidation.\n-Participants within 15 months from diagnosis and 120 days after last ASCT or consolidation treatment, if performed, who achieved at least a partial response (PR), according to IMWG criteria\n-Participants willing and able to follow the trial procedures\n-Participants must understand and voluntary sign an ICF prior to any study related assessment/procedurs being conducted\n-Age ≥18 years\n-ECOG performance status 0-1\n-A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) and must: -\tHave two negative pregnancy tests as verified by the Investigator prior to starting trial treatment. She must agree to ongoing pregnancy testing during the course of the trial, and after end of trial treatment. This applies even if the participant practices true abstinence* from heterosexual contact. -\tEither commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the trial treatment (including dose interruptions), and for at least 28 days after the last dose of CC-220."}

Exclusion criteria

• {"criterion_text":"-Systemic AL amyloidosis or plasma cell leukemia (>2.0x109/L circulating plasma cells by standard differential) or Waldenstrom’s macroglobulinemia\n-Participant has current or prior use of immunosuppressive medication within 14 days prior to starting therapy with iberdomide (exceptions are intranasal, inhaled, topical or local steroids injections; systemic corticosteroids at doses not exceeding 10 mg/day of prednisone or equivalent; steroids as premedication for hypersensitivity reactions)\n-Participant has taken a strong inhibitor or inducer of CYP3A4/5 including grapefruit, St John’s wort or related products within 2 weeks prior to dosing and during the course of trial\n-Participant known to test positive for HIV or have active hepatitis A, B or C\n-Participant is unable or unwilling to undergo protocol required thromboembolism prophylaxis\n-Participant is a female who is pregnant nursing or breastfeeding or who intends to become pregnant during the participation\n-Baseline lab values: -\tCreatinine clearance ≤30 ml/min. -\tSignificant hepatic dysfunction (total bilirubin > 1.5x ULN or AST/ALT > 2.5x ULN), or > 3.0 mg/dL for participants with documented Gilbert’s syndrome unless related to myeloma -\tCorrected serum calcium>13.5 mg/dL (3.4 mmol/L)\n-Any clinical condition at screening that would preclude participant from completing the trial\n-Participant has known meningeal involvement of multiple myeloma\n-History of active malignancy during the past 5 years, except squamous cell and basal cell carcinomas of the skin and carcinoma in situ of the cervix or breast and incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is cured, or malignancy that in the opinion of the local investigator, with concurrence with the principal investigator, is considered cured with minimal risk of recurrence within 3 years.\n-Participant with any one of the following: clinically significant abnormal electrocardiogram (ECG) findings at screening; congestive heart failure (New York Heart Association Class III or IV); myocardial infarction within 12 months prior to starting iberdomide; unstable or poorly controlled angina pectoris, including Prinzmetal variant; clinically significant pericardial disease\n-Peripheral neuropathy of ≥grade 2.\n-Participant has any concurrent severe and/or uncontrolled medical condition or psychiatric disease that is likely to interfere with trial procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this trial or that confounds the ability to interpret data from the trial.\n-Participant with gastrointestinal disease that may significantly alter the absorption of iberdomide\n-Participant with known history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide\n-Participant with known or suspected hypersensitivity to excipients contained in the formulation of iberdomide"}

Primary endpoints

• {"endpoint_text":"-Response improvement rate within 6 months will be measured as the number of participants that improve response according to IMWG criteria (from PR to ≥VGPR; from VGPR to ≥CR; from CR to >sCR) within the end of sixth cycle of treatment.","definition_or_measurement_approach":"Measured as the number of participants whose response improves according to IMWG criteria (from PR to ≥VGPR; from VGPR to ≥CR; from CR to >sCR) by the end of the sixth cycle of treatment (i.e., within 6 months)."}

Secondary endpoints

• {"endpoint_text":"-TTP will be measured by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmation to the date of first observation of PD, or deaths for PD. Participants who have not progressed or who withdraw from the trial or die from causes other than PD will be censored at the time of the last disease assessment. Participants lost to FU will also be censored at the time of last complete disease assessment.","definition_or_measurement_approach":"Measured from date of start of therapy (protocol) and by ITT from eligibility confirmation to first observation of progressive disease (PD) or death due to PD; censoring rules specified for withdrawal, no progression, lost to follow-up."}
• {"endpoint_text":"-PFS will be measured by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmation to the date of first observation of PD, or death from any cause as an event. Participants who have not progressed or who withdraw from the trial or who were lost to FU will be censored at the time of the last disease assessment.","definition_or_measurement_approach":"Measured from start of therapy (protocol) and by ITT from eligibility confirmation to first observation of PD or death from any cause; censoring at last disease assessment for non-progressors/withdrawals/lost to follow-up."}
• {"endpoint_text":"-TNT will be measured by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmation to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event. Participants who have not progressed or who withdraw from the trial will be censored at the time of the last disease assessment. Participants lost to FU will also be censored at the time of last contact.","definition_or_measurement_approach":"Measured from start of therapy (protocol) and by ITT from eligibility confirmation to date of next anti-myeloma therapy; death before next therapy counts as event; censoring rules provided."}
• {"endpoint_text":"-PFS2 will be measured by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmationto the date of observation of second disease progression (i.e. progression after the second line of therapy) or death to any cause as an event. In case of date of second progression is not available, date of start of third line treatment can be used.","definition_or_measurement_approach":"Measured from start of therapy (protocol) and by ITT from eligibility confirmation to second disease progression (after second-line therapy) or death; if second progression date unavailable, start of third-line treatment may be used."}
• {"endpoint_text":"-OS is defined by protocol from the date of start of therapy and according to ITT from the date of eligibility confirmation to the date of death, regardless cause of death. Participants who withdraw consent will be censored at the time of withdrawal. Participants who are still alive at the cut-off date of final analysis will be censored at the date of last contact. Participants lost to FU will also be censored at the time of last contact.","definition_or_measurement_approach":"Overall survival measured from start of therapy (protocol) and by ITT from eligibility confirmation to date of death from any cause; censoring rules specified."}
• {"endpoint_text":"-Response rate (sCR, CR, VGPR) will be evaluated according to IMWG Response criteria","definition_or_measurement_approach":"Response categories (sCR, CR, VGPR) evaluated per IMWG response criteria."}
• {"endpoint_text":"-Rate of NGF Minimal residual disease (MRD) conversion from positive to negative","definition_or_measurement_approach":"Measured as rate of conversion from MRD-positive to MRD-negative by next-generation flow (NGF)."}
• {"endpoint_text":"-The MRD conversion rate at 6 months is determined as the proportion of participants with MRD negativity (≥10-5 sensitivity level, by NGF) after 6 months converted from status as Positive at screening.","definition_or_measurement_approach":"Proportion of participants who were MRD-positive at screening and are MRD-negative (sensitivity ≥10^-5 by NGF) at 6 months."}
• {"endpoint_text":"-The MRD conversion rate at 12 months is determined as the proportion of participants with MRD negativity (≥10-5 sensitivity level, by NGF) after 12 months converted from status as Positive at screening. Participants who withdraw from the trial or are lost to follow up before post 12 months MRD evaluation, the best MRD assessment will be considered.","definition_or_measurement_approach":"Proportion of participants MRD-positive at screening converting to MRD-negative (≥10^-5 by NGF) at 12 months; best available MRD assessment used if post-12-month evaluation missing."}
• {"endpoint_text":"-The best MRD conversion rate within 12 months is determined as the proportion of participants with MRD negativity (≥10-5 sensitivity level, by NGF) within 12 months converted from status as Positive at screening. The best MRD assessment will be considered. Participants who withdraw from the trial or are lost to follow up before MRD evaluation, the best MRD assessment will be considered.","definition_or_measurement_approach":"Best observed MRD conversion to negativity (≥10^-5 by NGF) within 12 months among those MRD-positive at screening."}
• {"endpoint_text":"-The analysis of safety as defined by type, frequency and severity will be done primarily by tabulation of the incidence of AEs as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. In the by-participant analysis, a participant having the same event more than once will be counted only once. AEs will be summarized by worst CTCAE grade","definition_or_measurement_approach":"Safety analysed by tabulating incidence of adverse events per NCI CTCAE v5.0; by-participant counting and summary by worst CTCAE grade."}
• {"endpoint_text":"-Dose reduction will be done primarily by tabulation of the incidence of participant with at least one dose reduction and causes.","definition_or_measurement_approach":"Tabulation of number of participants with ≥1 dose reduction and reasons."}
• {"endpoint_text":"-Relative dose will be evaluated consider the ratio between the administered and the planned dose.","definition_or_measurement_approach":"Relative dose assessed as ratio of administered to planned dose."}
• {"endpoint_text":"-Time to discontinuation for toxicity will be measured from the date of first dose of study drugs to the date of discontinuation due to AE or Death for AE/SPM. Participants who discontinued drugs due to PD, or death for cause other than AE/SPM will be considered a competing event. Participants has not discontinued and are still alive and on treatment at the cut-off date of final analysis will be censored at the cut-off date.","definition_or_measurement_approach":"Measured from first dose to discontinuation due to AE or death from AE/SPM; competing events and censoring rules defined."}
• {"endpoint_text":"-Quality of life defined by EORTC QLQ-C30.","definition_or_measurement_approach":"Quality of life assessed using the EORTC QLQ-C30 questionnaire."}
• {"endpoint_text":"-Determine whether tumor response and outcome (PFS, PFS2, TTP, TNT and OS) may change in subgroups with different prognosis according to current prognostic factors.","definition_or_measurement_approach":"Subgroup analyses to evaluate whether tumor response and outcomes (PFS, PFS2, TTP, TNT, OS) differ by prognostic factor-defined subgroups."}

Italy

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

579

Number Of Sites

9

Number Of Participants

33

Greece

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

09-03-2026

Processing Time Days

550

Number Of Sites

2

Number Of Participants

23

Netherlands

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

551

Number Of Sites

4

Number Of Participants

24

France

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

551

Number Of Sites

4

Number Of Participants

40

Primary sponsor

Full Name

European Myeloma Network B.V.

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands

Third parties

• {"country":"Netherlands","full_name":"Stichting Amsterdam UMC","duties_or_roles":"For substudy: flow cytometry; code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Central depot for the IMP","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)","duties_or_roles":"MRD by NGF; For substudy: Monitoring immune competence at the single cell level; code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Greece","full_name":"Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.","duties_or_roles":"codes 1 and 12","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Fisher Clinical Services UK Limited","duties_or_roles":"Central depot for the IMP","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Celgene International II SARL","duties_or_roles":"code 14; contract with central depots","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Emn Trial Office S.r.l. Impresa Sociale","duties_or_roles":"Other - MRD by NGF for Greece and Italy Laboratory analysis; code 4","organisation_type":"Laboratory/Research/Testing facility"}

Co-sponsors

• Emn Trial Office S.r.l. Impresa Sociale