Iberdomide: IBERDOMIDE (CC220) IN MAINTENANCE AFTER AUTOLOGOUS STEM CELL TRANSPLANTION IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS
Study summary
This is a phase II study to evaluate the efficacy and safety of different doses of iberdomide continuous therapy as maintenancetreatment after transplant.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Subjects 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-
* Subjects with complete baseline evaluation at the time of diagnosis according to revised International Staging System (R-ISS) (cytogenetic profile, ISS and LDH)
* Subjects 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.
* Subjects within 12 months from diagnosis and 120 days after last ASCT, who achieved at least a partial response (PR) after ASCT, according to IMWG criteria
* Subjects willing and able to follow the trial procedures
* Subjects must understand and voluntary sign an ICF prior to any study related assessment/procedurs being conducted
* Age ≥18 years
* ECOG performance status 0-1
* 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:
1. Have two negative pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence\* from heterosexual contact.
2. Either 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 study treatment (including dose interruptions), and for at least 28 days after the last dose of CC-220, 90 days after the last dose of cyclophosphamide, whichever is longer. Contraception requirements are detailed in Appendix H.
* Male subjects must:
a. 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 study, during dose interruptions and for at least 90 days following the last dose of study 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 subject. \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.\]
* Males must agree to refrain from donating sperm while on study treatment, during dose interruptions and for at least 90 days following last dose of study treatment.
* All subjects 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 study treatment.
* All male and female subjects must follow all requirements defined in the Pregnancy Prevention Program (v5.1). See Appendix I for CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.
* Subject agree to refrain from donating blood while on iberdomide, during dose interruption and for at least 28 days following the last iberdomide dose
* Baseline values:
ANC ≥1.0 x 109/L without use of growth factors; PLTs≥75 x109/L (transfusions within 14 days from Day1 cycle 1 to achieve this cut off are not allowed); Hb \>8 g/dL (transfusions within 14 days from Day1 cycle 1 to achieve this cut off are not allowed); • Life expectancy ≥ 3 months
Exclusion Criteria:
* • Systemic AL amyloidosis or plasma cell leukemia (\>2.0x109/L circulating plasma cells by standard differential) or Waldenstrom's macroglobulinemia
* Subject has known meningeal involvement of multiple myeloma
* 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.
* Subject 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
* Peripheral neuropathy of ≥grade 2.
* Subject 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.
* Subjects with gastrointestinal disease that may significantly alter the absorption of iberdomide
* Subject with known history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide
* Subject with known or suspected hypersensitivity to excipients contained in the formulation of iberdomide
* Subjects 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)
* Subject 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 study
* Subject known to test positive for HIV or have active hepatitis A, B or C
* Subjects is unable or unwilling to undergo protocol required thromboembolism prophylaxis
* Subject is a female who is pregnant nursing or breastfeeding or who intends to become pregnant during the participation
* Baseline lab values:
* Creatinine clearance ≤30 ml/min.
* Significant hepatic dysfunction (total bilirubin \> 1.5x ULN or AST/ALT \> 2.5x ULN), or \> 3.0 mg/dL for subjects with documented Gilbert's syndrome unless related to myeloma
* Corrected serum calcium\>13.5 mg/dL (3.4 mmol/L) • Any clinical condition at screening that would preclude subject from completing the study
Primary outcome measure(s)
Efficacy: rate of improvement in response with iberdomide maintenance after autologous stem cell transplantation (ASCT) — 6 months of treatment Response improvement rate within 6 months will be measured as the number of subjects 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.
Rate of dose reductions/discontinuations with iberdomide maintenance after ASCT — 6 months of treatment Dose reductions/discontinuation rate within 6 months will be measured as the number of subjects that discontinued treatment or have a dose modification within the end of sixth cycle of treatment
Trial sites (22)
Facility
City
Region
Status
Centre Hospitalier Universitaire de Bordeaux
Bordeau
France
Centre Hospitalier Universitaire de Dijon
Dijon
France
CHU Hôtel-Dieu, 1, place Alexis Ricordeau, 44093 NANTES Cedex 1, FRANCE
Nantes
France
CHU Hôtel-Dieu
Nantes
France
Saint Antoine Hospital, Hematology Department
Paris
France
C.H.U. Strasbourg
Strasbourg
France
Institut Universitaire Du Cancer De Toulose
Toulouse
France
Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens
Athens
Greece
Theagenio Cancer Hospital
Thessaloniki
Greece
A.O.U. Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi di Ancona
Ancona
Italy
A.O.U. di Bologna - Policlinico S. Orsola Malpighi
Bologna
Italy
Ospedale Generale Regionale-Divisione di Ematologia e Centro Trapianto Midollo Osseo
Bolzano
Italy
A.O. Spedali Civili di Brescia
Brescia
Italy
A.O.U. Careggi
Florence
Italy
A.O.U. Policlinico S. Martino - Ematologia
Genova
Italy
Policlinico S. Matteo Fondazione IRCCS
Pavia
Italy
A.O. S. Maria
Terni
Italy
A.O.U. Città della Salute e della Scienza di Torino-Ematologia U
Torino
Italy
Vrije Universiteit Medical Center (VUMC)
Amsterdam
Netherlands
Breda-Amphia Ziekenhuizen
Breda
Netherlands
Albert Schweitzer Hospital
Dordrecht
Netherlands
Erasmus University Medical Center
Rotterdam
Netherlands
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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