The goal of this phase 2 clinical trial is to learn if patients with Multiple Myeloma who are minimal residual disease positive after initial therapy (including an autologous stem cell transplant \[ASCT\]) will benefit from maintenance therapy with Iberdomide and subcutaneous (SC) Daratumumab. The main questions it aims to answer are:
* Assess if giving Iberdomide and the SC Daratumumab in the maintenance setting is an effective treatment and warrants further investigation in patients with residual disease * Is giving Iberdomide and SC Daratumumab maintenance post ASCT a safe option
Participants will:
* provide informed consent and complete screening assessments for eligibility within 28 days of starting treatment * Screening assessments include specific laboratory tests, a medical history assessment and a physical examination (including temperature, pulse, blood pressure, respirations, height and weight), an assessment of your heart function, a breathing test, cancer imaging, a bone marrow biopsy, minimal residual disease testing (MRD) and a questionnaire * If eligible, patients will start treatment with Iberdomide (1.0 mg on day 1-21 of each 28 day cycle, with an increase to 1.3 mg on Cycle 4 if the 1.0 mg dose was tolerated, to a maximum of 26 cycles or progressive disease, whichever is first) and SC Daratumumab (1800 mg SC on days 1, 8, 15 and 22 of cycle 1 and 2, then 1800 mg SC on Day 1 and 15 of cycle 3-6 and 1800 mg SC on Day 1 for cycles 7-26 to a maximum of 26 cycles or progressive disease, whichever is first) * while receiving treatment on study, physical exams (including temperature, pulse, blood pressure, respirations, height and weight), toxicity assessments, laboratory assessments and questionnaires will be done at various times over the course of the 26 cycles * an MRD assessment is required at 6, 12 and 24 months after starting treatment * End of treatment will occur once 26 cycles are completed, or cancer has progressed whichever comes first. At that time, specific laboratory tests, a physical examination (including temperature, pulse, blood pressure, respirations, height and weight), cancer imaging, a bone marrow biopsy and minimal residual disease testing (MRD) will occur.
Multiple Myeloma patients who have received prior DARA-containing induction therapy and have attained at least a partial response.
Patients who have completed Autologous Stem Cell Transplant (ASCT) 90-150 days prior to registration, without any post-ASCT therapy and without post-ASCT disease progression (according to IMWG criteria)
Patients who are Minimal Residual Disease positive (MRD (+)) as measured by the ClonoSEQ assay using a sensitivity of 10-5, measured 90-150 days following ASCT.
Prior DARA-containing induction therapy (at least 3 cycles), attaining at least a partial response.
Active HIV, or HCV (defined as detectable viremia for any of these conditions).
Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen[HBsAg]). Patients with resolved infection (i.e., patients who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time PCR (polymerase chain reaction) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded.
Unable to assess MRD status at entry or is MRD(-) at 10-5 threshold at entry
Heart attack or stroke within 90 days of study enrollment
Single group
Iberdomide
DrugIberdomide 1.0mg daily for days 1-21 of a 28-day cycle, an increase to 1.3 mg daily on Day 1-21 of a 28-day cycle is allowed at cycle 4 or higher if the 1.0 mg dose was well tolerated.
Daratumumab/rHuPH20 Co-formulation
DrugDaratumumab/rHuPH20 will be dosed as follows: * Daratumumab/rHuPH20 1800 mg SC days 1, 8, 15, 22 (28-day cycle; cycles 1-2) * Daratumumab/rHuPH20 1800 mg SC days 1, 15 (28-day cycle; cycles 3-6) * Daratumumab/rHuPH20 1800 mg SC day 1 (28-day cycle; cycles 7-26)
Rate of MRD (-) at 12 months
Summarized by a binomial response rate and its associated 2-sided 90% confidence interval (CI) using Pearson-Klopper method.
Rate of Sustained MRD (-)
The rate at which IMWG (International Myeloma Working Group) response category improves by at least one grade during maintenance and the rate of treatment interruptions and dosage adjustments during maintenance will be summarized by a binomial response rate and 2-sided 95% CI using Pearson-Klopper method. Two or more consecutive negative measurements during therapy which are at least 6 months apart.
Progression-Free Survival
Duration from the start date of treatment until the date of progression (as defined by IMWG criteria) or death from any cause.
Progression Free Survival
Duration from the start date of treatment until the date of progression (as defined by IMWG criteria) or death from any cause.
Overall Survival
Duration from the start date of treatment until the date of death from any cause
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Barbara Ann Karmanos Cancer Institute
Lead sponsor
Bristol-Myers Squibb
Collaborator
Janssen Pharmaceuticals
Collaborator
Multiple Myeloma Research Consortium
Collaborator
