IRB Study Number 23-393
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
To compare the efficacy of iberdomide versus lenalidomide in participants with NDMM after ASCT, as measured by PFS
Secondary Objectives
To compare the MRD negativity rate (at a threshold of 10–5 by next-generation flow) in participants with a response of CR or better at 12 (± 3) months of maintenance treatment with iberdomide versus lenalidomide
To evaluate OS in participants with NDMM after ASCT treated with iberdomide compared to lenalidomide
Inclusion Criteria
1) Signed Written Informed Consent
a) Participants must have signed and dated an Institutional Review Board (IRB) /Independent Ethics Committee (IEC) approved written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
2) Type of Participant and Target Disease Characteristics
a) At the time of diagnosis:
i) Participants with confirmed diagnosis of symptomatic MM, defined as monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy-proven plasmacytoma and documented MM, satisfying at least 1 of the myeloma-defining events as detailed in the International Myeloma Working Group (IMWG) criteria for the diagnosis of myeloma.60 (Refer to Appendix 11: International Myeloma Working Group Diagnostic Criteria for Multiple Myeloma)
b) At enrollment:
i) Eastern Cooperative Oncology Group performance status (ECOG) performance status score of 0, 1, or 2. (Refer to Appendix 7: ECOG performance status) ii) Participant has received 3 to 6 cycles of an induction therapy that includes a PI and IMiD (eg, VTd, RVd) with or without a CD38 monoclonal antibody, or VCd, and followed by a single or tandem ASCT. Post-stem cell transplant consolidation is permitted.
iii) Participants within 12 months from initiation of induction who achieved at least a PR after ASCT with or without consolidation, according to IMWG 2016 criteria.61 (Refer to Appendix 6: International Myeloma Working Group Uniform Response Criteria)
(1) For participants who have not received consolidation therapy, the participant must be within 120 days posttransplant at the time of randomization.
(2) For participants treated with consolidation therapy, the participant must be within 30-60 days of the last dose of consolidation therapy at the time of randomization and within 180 days posttransplant at the time of randomization.
iv) Participants are willing and able to follow the study procedures.
v) Availability of complete documentation for:
(1) Details of initial disease state, initial therapy, and response
(2) Cytogenetics assessment at diagnosis or any timepoint prior to ASCT (If local cytogenetic data unavailable, archival sample collected from any time point before ASCT should be submitted to central laboratory for FISH analysis)
(3) ISS staging at diagnosis (requiring serum β2 Microglobulin and albumin results at diagnosis)
3) Age of Participant:
a) Participant is ≥ 18 years of age at the time of signing the ICF.
4) Reproductive Status
Investigators shall counsel females of childbearing potential (FCBP) (as defined in Appendix 4 and Appendix 5) participants, and male participants who are sexually active with FCBP, on the importance of pregnancy prevention, the implications of an unexpected pregnancy, and the potential of fetal toxicity occurring due to transmission of study intervention, present in seminal fluid, to a developing fetus, even if the participant has undergone a successful vasectomy or if the partner is pregnant.
The investigator shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
Local laws and regulations may require the use of alternative and/or additional contraception methods.
Participants must agree to refrain from donating blood while on the study treatment, during dose interruptions, and for at least 28 days following the last dose of the study treatment.
a) Female Participants:
i) Female participants must have documented proof that they are not of childbearing potential.
(1) Females who are not of childbearing potential (as defined in Appendices 4 and 5) are exempt from contraceptive requirements.
ii) FCBP must have two negative pregnancy tests (sensitivity of at least 25 mIU/mL) prior to starting the study treatment. The first pregnancy test must be performed within 10 to 14 days prior to the start of study treatment and the second pregnancy test must be performed within 24 hours prior to the start of study treatment. The participant may not receive study treatment until the study doctor has verified that the results of these pregnancy tests are negative.
Additional requirements for pregnancy testing during and after study intervention are in Section 2: Schedule of Activities.
The investigator is responsible for the review of the medical history, menstrual history, and recent sexual activity to potentially decrease the risk for inclusion of a woman with an undetected pregnancy.
iii) FCBP and male participants who are sexually active with FCBP must agree to follow instructions for method(s) of contraception as described below and included in the ICF.
FCBP are permitted to use hormonal contraception methods (as described in Appendix 4:
Iberdomide Pregnancy Prevention Plan for Subjects in Clinical Trials (v7.0) and the Lenalidomide Pregnancy Prevention Plan for Subjects in Clinical Trials (v4.0) (Appendix 5).
iv) A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
(1) Is not an FCBP OR
(2) Is an FCBP and either commits 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, 2 forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting the study treatment, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of iberdomide or lenalidomide.
b) Male Participants:
i) Azoospermic males are not exempt from contraceptive requirements and will be required to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with a FCBP, even if the participant has undergone a successful vasectomy or if the partner is pregnant.
ii) Male participants must practice true abstinence* (which must be reviewed on a monthly basis and source documented) or agree to always use a latex or other synthetic condom during any sexual activity (eg, vaginal, anal, oral) with a FCBP, even if the participant has undergone a successful vasectomy or if the partner is pregnant or breastfeeding. Male participants should continue to use a condom during the intervention period and for at least 28 days after the last dose of iberdomide, or 28 days after last dose of lenalidomide.
iii) Female partners of male participants should be advised to use a highly effective method of contraception during the intervention period and for at least 28 days after the last dose of iberdomide, or 28 days after last dose of lenalidomide for the male participant.
iv) Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from sexual activity or use a male condom during any sexual activity (eg, vaginal, anal, oral), even if the participant has undergone a successful vasectomy, during the intervention period and for at least 28 days after the last dose of iberdomide, or 28 days after last dose of lenalidomide.
v) Male participants must agree to refrain from donating sperm while on the study treatment, during dose interruptions, and for at least 28 days following last dose of iberdomide or 28 days after the last dose of lenalidomide, as applicable.
vi) Breastfeeding partners of male participants should be advised to consult their health care provider about using appropriate highly effective contraception during the time the male participant is required to use condoms.
Exclusion Criteria
1) Medical Conditions
a) Participant has progressive disease or clinical relapse (as defined by IMWG response criteria)61 following ASCT with or without consolidation or is not responsive to primary therapy.
b) Participant has systemic amyloid light-chain amyloidosis or plasma cell leukemia (> 2.0 x 109/L circulating plasma cells by standard differential) or polyneuropathy, organomegaly, endocrinopathy, monoclonal-protein, and skin abnormalities (POEMS syndrome) or Waldenstrom’s macroglobulinemia.
c) Participant has smoldering myeloma, solitary plasmacytoma or nonsecretory myeloma.
d) Participant has known central nervous system/meningeal involvement of MM.
e) Participant has prior history of malignancies, other than MM, unless the participant has been free of the disease for ≥ 5 years, except for the following noninvasive malignancies:
i) Basal cell carcinoma of the skin
ii) Squamous cell carcinoma of the skin in situ (stage 0)
iii) Carcinoma in situ of the cervix
iv) Carcinoma in situ of the breast
v) Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative
f) Participant has clinically significant impaired cardiac function, or cardiac disease including any of the following:
i) Myocardial infarction within 6 months before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure New York Heart Association Class III-IV) or pericardial disease.
ii) Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities, including prolongation of QT interval on screening ECG as defined by a QTc interval > 470 msec using Fridericia’s QT correction formula
g) Peripheral neuropathy of Grade ≥ 2.
h) 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.
i) Participant has had severe acute respiratory syndrome coronavirus 2 infection within 14 days for mild or asymptomatic infections or 28 days for severe/critical illness prior to initiating study treatment.
j) Participant has received major surgery (as defined by the investigator) within 28 days of initiating study treatment.
k) Participant has active systemic infection that is likely to interfere with the study procedures or results or that, in the opinion of the investigator, would constitute a hazard for participating in this study.
l) Participant has gastrointestinal disease that may significantly alter the absorption of iberdomide or lenalidomide.
m) Participant has received a live vaccine within 3 months of initiating study treatment.
n) Known active hepatitis A, B, or C virus infection, or participant is known to be seropositive for human immunodeficiency virus (HIV).
2) Reproductive Status
a) Women who are breastfeeding
b) Participant is a female who is pregnant, nursing, or breastfeeding, or who intends to become pregnant during participation in the study.
3) Prior/Concomitant Therapy
a) Participant is unable or unwilling to undergo protocol-required thromboembolism prophylaxis.
b) Inability to comply with restrictions and prohibited treatments as listed in Section 7.7: Concomitant Therapy.
c) Participant has current or prior use of immunosuppressive medication within 14 days prior to starting therapy with study treatment (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).
d) Concurrent administration of a strong inhibitor or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment). Refer to Appendix 10: CYP3A4/5 strong inhibitor and inducers.
e) Received any prior BCMA-directed therapy.
f) Any previous therapy with an immune cell redirecting agent or gene modified adoptive cell therapy (e.g., chimeric antigen receptor modified T cells, NK cells).
4) Physical and Laboratory Test Findings
a) Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population.
b) Participant has any of the following laboratory test results abnormalities:
i) ANC < 1,000/μL. It is not permissible to administer granulocyte colony-stimulating factor (GCSF) to achieve minimum ANC levels within 14 days prior to screening.
ii) Platelet count: < 75,000 /μL. It is not permissible to transfuse participants to achieve minimum platelet counts within 7 days prior to screening complete blood count.
iii) Hemoglobin < 8 g/dL (< 4.9 mmol/L). It is not permissible to transfuse participants within 7 days prior to screening.
iv) Creatinine clearance (CrCL) < 30 mL/min or requiring dialysis.
v) Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L).
vi) Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN).
vii) Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for participants with documented Gilbert’s syndrome.
5) Allergies and Adverse Drug Reactions
a) Participant with known history of anaphylaxis or hypersensitivity to thalidomide, pomalidomide, or lenalidomide.
b) Participant with known or suspected hypersensitivity to excipients contained in the formulation of iberdomide or lenalidomide.
6) Other Exclusion Criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific circumstances and only in countries where local regulations permit, a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply, and Sponsor approval is required.)
b) Participant received any investigational agent within 28 days.
i) Participants who are participating in other interventional trials may not participate in Sponsor’s clinical trials, except for those who have completed treatment with the prior investigational agent(s) and are currently in LTFU.
