Iberdomide vs. Iberdomide Plus Isatuximab Maintenance Therapy Post ASCT in Newly Diagnosed Multiple Myeloma

Korábbi kezelés

• Patient has known hypersensitivity (or contraindication) to any of the components of study therapy that are not amenable to premedication with steroids or H1 blockers and that would prohibit further treatment with these agents (e.g. known intolerance or hypersensitivity to infused proteins products, sucrose, histidine, and polysorbate 80 as well as intolerance to arginine and Poloxamer 188)
• Patients currently being treated with strong inhibitors or inducers of CYP3A4/5
• Previous systemic anti-myeloma treatment other than administered within the GMMG-HD8 / DSMM XIX trial or other than defined in the inclusion criteria above (including up to two cycles cycle high dose melphalan therapy (HDM) and autologous stem cell transplantation (ASCT). Local, consolidative radiotherapy for myeloma disease is permitted unless performed in case of progressive disease according to IMWG criteria
• Patients with a history of any active malignancy during the past 5 years with the exception of following malignancies after curative therapy: basal cell carcinoma of the skin, squamous cell skin carcinoma, stage 0 cervical carcinoma or any in situ malignancy. A history of an early stage malignancy during the past 5 years may be acceptable, however, in this case the GMMG study office has to be consulted prior to study inclusion
• Participant has any concurrent severe and/or uncontrolled medical condition or psychiatric 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 or that confounds the ability to interpret data from the study
• Participation in other interventional clinical trials. This does not include long-term follow-up periods without active drug treatment of previous studies during the last 6 months.

Más betegség

• Subjects with gastrointestinal disease that may significantly alter the absorption of iberdomide
• Patients with a history of serious allergic reaction to another immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide)", as angioedema and severe dermatologic reactions, including Grade 4 rash and exfoliative or bullous rash
• Severe cardiac dysfunction (NYHA classification III-IV)
• Patients with active or uncontrolled hepatitis B or C or detectable liver disease due to hepatitis B or C. In case of history of hepatitis B or C, it must be clarified whether it has been overcome and negative circulating HBV-DNA or HCV-RNA must be provided. Positive hepatitis B status may only be acceptable in absence of circulating HBV-DNA or signs of chronic or acute infection and if an adequate prophylaxis is being implemented during the course of the study. Prophylaxis for patients with history of hepatitis B or C should be set on a patient individual basis.
• HIV positivity
• Patients with active, uncontrolled infections
• Patients with acute diffuse infiltrative pulmonary and/or pericardial disease
• Autoimmune haemolytic anaemia with positive indirect Coombs test or immune thrombocytopenia

Laborértékek

• Significant hepatic dysfunction (ASAT and/or ALAT ≥ 3 times normal level and/or serum bilirubin ≥ 1.5 times normal level if not due to hereditary abnormalities as Gilbert's disease), unless related to MM or HDM/ASCT.
• Patients with severe renal insufficiency (Creatinine Clearance < 30ml/min) or requiring hemodialysis
• Platelet count < 75 x 109/l
• Haemoglobin ≤ 8.0 g/dl, unless related to MM
• Absolute neutrophil count (ANC) < 1.0 x 109/l (the use of colony stimulating factors within 14 days before the test is not allowed)
• Corrected serum calcium > 14 mg/dl (> 3.5 mmol/l)

Egyéb

• Systemic AL amyloidosis (except for localized AL amyloidosis limited to the skin or the bone marrow), plasma cell leukemia or polyneuropathy, organomegaly, endocrinopathy, monoclonal-protein and skin abnormalities or Waldenström macroglobulinemia.
• Patients with peripheral neuropathy or neuropathic pain, grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE, version 5.0)
• Unable or unwilling to undergo thromboprophylaxis
• Pregnancy and lactation
• Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

• Prior inclusion and treatment within the GMMG-HD8 / DSMM XIX trial OR
• Received a quadruplet induction/consolidation therapy that consists of a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) [e.g., bortezomib, thalidomide and dexamethasone, or bortezomib, lenalidomide and dexamethasone] with an anti-CD38 monoclonal antibody (isatuximab or daratumumab)
• Post HDM/ASCT consolidation containing similar substances as induction therapy is permitted
• Induction and consolidation therapy should make up a total of at least 4 up to 6 cycles, with a maximum of 2 consolidation cycles post HDM/ASCT AND
• Received at least one cycle high dose melphalan therapy (HDM) and autologous stem cell transplantation (ASCT)
• At least Partial Response (PR) according to IMWG criteria at inclusion in the trial
• Age of at least 18 years at trial inclusion
• WHO performance status of 0, 1, or 2
• Negative pregnancy test at inclusion (women of childbearing potential)
• For all men and women of childbearing potential: patients must be willing and capable to use adequate contraception during the complete therapy
• Ability of patient to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrolment in the trial)