Iberdomide as Maintenance Therapy for the Treatment of Multiple Myeloma in Patients Who Underwent Stem Cell Transplant and had Previous Lenalidomide Maintenance Therapy
This phase II trial tests whether iberdomide works as maintenance therapy in treating patients with multiple myeloma who underwent a stem cell transplant and received the standard drug lenalidomide as maintenance therapy. Maintenance therapy is given after stem cell transplant to prevent the cancer from returning. Iberdomide is a type of drug called a cereblon-modifying (CM) agent. It works by targeting and destroying proteins that help produce myeloma cancer cells. By destroying these proteins, iberdomide may prevent cancer from returning or getting worse.
Inclusion Criteria
- Histologic confirmation of multiple myeloma by the enrolling institution. Cohort specific eligibility below
- Age 18-75
- Karnofsky performance greater than or equal to 70
- Recovered to grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding grade 2 neuropathy
- Absolute neutrophil count (ANC) greater than or equal to 1,000/mm^3 without filgrastim use in the prior 14 days
- Platelet count greater than 75,000/mm^3 (without platelet transfusion in the previous 7 days or thrombopoietin mimetics in the previous 28 days)
- Hemoglobin greater than 8 g/dL (without red blood cell transfusion in the previous 7 days)
- Creatinine clearance (CrCl) greater than or equal to 30 mL/min, measured or estimated by Cockcroft-Gault equation
- Corrected serum calcium less than or equal to 13.5 mg/dL
- Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN)
- Serum total bilirubin less than or equal to 2 x ULN. Patients who have been diagnosed with Gilbert’s disease are permitted to exceed the defined bilirubin value of 2 x ULN
- International ratio (international normalized ratio [INR]) or partial thromboplastin time (PTT) less than 1.5 x ULN unless on therapeutic anticoagulation
- Females of childbearing potential have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL * A female of childbearing potential (FCBP) is a female who: ** Has achieved menarche at some point ** Has not undergone a hysterectomy or bilateral oophorectomy ** 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: *** 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 *** 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 iberdomide
- COHORT 1: Received a single prior autoHCT with melphalan >= 140mg/m^2 and a >= 2 x 10^6 CD34+ cells/kg (actual body weight) less than or equal to 15 months from initiation of systemic anti-myeloma therapy
- COHORT 1: Have been on lenalidomide maintenance at a dose of >= 5 mg every other day for at least 6 months
- COHORT 1: Have achieved a very good partial response (VGPR) or less to treatment by International Myeloma Working Group Criteria
- COHORT 1: Be within 15 months of their autoHCT
- COHORT 2: Have received 2 to 3 prior lines of systemic anti-myeloma therapy +/- prior autoHCT
- COHORT 2: Have had lenalidomide maintenance therapy after a line of treatment prior to the salvage autoHCT
- COHORT 2: Have undergone salvage autoHCT consolidation with a high dose melphalan based conditioning regimen within the prior 2-6 months
- Male subjects must practice complete abstinence (True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [e.g. calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception.) or agree to use a condom during sexual contact with a pregnant female or a FCBP while taking iberdomide, during dose interruptions and for at least 90 days following the last dose of iberdomide even he has undergone a successful vasectomy. 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
- All subjects must: * Understand that iberdomide could have potential teratogenic risk * Agree to abstain from donating blood while taking iberdomide and for 28 days following discontinuation of the iberdomide * Agree not to share iberdomide with another person * Other than the subject, FCBP and males able to father a child should not handle the investigational product (IP) or touch the capsules unless gloves are worn * Be counseled about pregnancy precautions and risks of fetal exposure as described in the Pregnancy Prevention Plan
Exclusion Criteria
- Prior allogeneic hematopoietic stem cell transplant
- Disease progression after most recent autoHCT prior to enrollment
- Known active central nervous system (CNS) involvement with MM
- Prior organ transplant requiring systemic immunosuppressive therapy
- History of a thromboembolic event while on full anticoagulation during prior therapy with an immunomodulatory agent (IMiD)
- Unwilling to take deep vein thrombosis (DVT) prophylaxis while on iberdomide maintenance
- History of greater than or equal to grade 2 hemorrhage within 30 days of enrollment
- History of plasma cell leukemia, Waldenstrom’s macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or clinically significant amyloidosis
- Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine or systemic steroids at any dose). Physiologic replacement, intermittent topical, inhaled or intranasal corticosteroids are allowed
- Seropositive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B (defined as positive hepatitis B surface antigen [HepBSAg] or hepatitis B core antibody [HepBcore Ab]) or C (hepatitis C antibody [Hep C Ab]), or acute hepatitis A. If any history of exposure to hepatitis B or C, then polymerase chain reaction (PCR) should be negative
- Prior malignancies except resected basal cell carcinoma or treated carcinoma in situ. Cancer treated with curative intent less than 5 years prior to enrollment will not be allowed unless approved by the Memorial Sloan Kettering (MSK) principal investigator (PI). Cancer treated with curative intent greater than 5 years prior to enrollment is allowed
- Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, or pomalidomide
- Uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment
- Serious medical of psychiatric illness likely to interfere with participation on this clinical study
- Unwilling or unable to provide informed consent
- Unable or unwilling to return to the transplant center for treatment and follow up
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05354557.
PRIMARY OBJECTIVE:
I. To estimate the 6-month complete response (CR) rate after iberdomide in multiple myeloma (MM) patients with suboptimal disease responses after an autologous hematopoietic stem cell transplantation (autoHCT) and lenalidomide maintenance or autoHCT performed in patients who had progressed on lenalidomide maintenance previously.
SECONDARY OBJECTIVES:
I. To estimate the 6-month response to treatment as determined by improved depth of response and conversion to minimal residual disease (MRD).
II. To estimate the disease progression and progression free survival at 6 months and 1 year.
III. To estimate the non-relapse mortality and overall survival at 6 months and 1 year.
IV. To estimate the incidence of grades 3-5 toxicities while on iberdomide maintenance.
EXPLORATORY OBJECTIVES:
I. To estimate the 12-month response to treatment as determined by improved depth of response and conversion to minimal residual disease (MRD).
II. To describe the immune reconstitution of patients and the changes in immune subsets between enrollment, 6 months, and 12 months on iberdomide.
III. To describe the mutational profile on samples at time of disease progression.
IV. To describe the patient reported outcomes using Patient Reported Outcomes Measurement Information System (PROMIS)-29 assessment.
OUTLINE:
Patients receive iberdomide orally (PO) daily on days 1-21 of each cycle. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo fludeoxyglucose F 18 (FDG) positron emission tomography (PET)/computed tomography (CT) scan at baseline, after 6 cycles and at end of treatment. Additionally, patients undergo bone marrow biopsy and aspiration and blood sample collection at baseline and throughout study.
After completion of study treatment, patients are followed up at years 2 and 3.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorGunjan L. Shah
- Primary ID22-040
- Secondary IDsNCI-2022-04102
- ClinicalTrials.gov IDNCT05354557