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Testing the Investigational Medication Combination of Teclistamab and Pomalidomide Compared to the Usual Treatment (Carfilzomib, Pomalidomide, and Dexamethasone) for Patients With Multiple Myeloma Who Have Relapsed Shortly After Treatment

RecruitingPhase 1, Phase 2Ages 18 Years - anyAllNational Cancer Institute (NCI)
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In plain words

What the trial is, and whether it could suit you

This phase Ib/II trial compares the effect of teclistamab and pomalidomide to standard treatment with carfilzomib, pomalidomide and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed). Teclistamab is a bispecific antibody that can bind to two different antigens at the same time. Teclistamab binds to B-cell maturation antigen (BCMA), a protein found on some B-cells and myeloma cells, and CD3 on T-cells (a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Pomalidomide is in a class of medications called immunomodulatory agents. It works by helping the immune system kill cancer cells and by helping the bone marrow to produce normal blood cells. Carfilzomib blocks the action of enzymes called proteasomes, which may help keep cancer cells from growing and may kill them. It is a type

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📋 Eligibility rules (as published)
Inclusion Criteria: * Patient must be ≥ 18 years of age * Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Patient must have an identifiable dominant sequence (clonotype) established based on Adaptive Biotechnologies clonoSEQ® assay for Phase II only * Patient must have multiple myeloma and meet both of the following criteria for the original diagnosis of myeloma following the International Myeloma Working Group (IMWG) myeloma diagnostic criteria: * Bone marrow plasmacytosis with ≥ 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma. * Tissue biopsy of any bone lesion or extramedullary plasmacytoma if applicable (positive/negative for clonal plasma cells) * Any one or more of the following symptomatic myeloma-defining events that prompted initiation of therapy as well as end-organ damage: * Anemia (hemoglobin value of \> 2 g/dL below the lower limit of normal, or a hemoglobin value \< 10 g/dL) * Hypercalcemia (serum calcium \> 1 mg/dL higher than the upper limit of normal or \> 11 mg/dL) * Bone disease (one or more osteolytic lesions on skeletal radiography, CT, or FDG-PET/CT) * Renal dysfunction (creatinine clearance \< 40 mL/min or serum creatinine \> 2 mg/dL). * Clonal bone marrow plasma cells (BMPCs) ≥ 60% * Involved/uninvolved serum free light chain ratio ≥ 100 * \> 1 focal lesions on magnetic resonance imaging (MRI) studies ≥ 5 mm * NOTE: Patients with smoldering myeloma (serum m protein ≥ 3 gm/dL or bone marrow plasma cells ≥ 10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) and monoclonal gammopathy of undetermined significance (serum m protein \< 3 gm/dL and bone marrow plasma cells \< 10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) are not eligible * Patient must have experienced relapse disease defined as relapse after one line of lenalidomide therapy including single agent lenalidomide or lenalidomide/dexamethasone or CD38 antibody/lenalidomide +/- dexamethasone. The relapse can be progressive disease as determined by the treating clinician and meeting measurable disease criteria * Patient must have received no more than two lines of IMWG defined therapy (induction +/- transplant + maintenance is considered a single line of therapy) * Patient must not receive non-protocol concurrent chemotherapy for the study disease, or any ancillary therapy considered investigational while participating in the study * Patient must have received an immunomodulatory drug (lenalidomide) and a CD38 antibody (daratumumab or isatuximab) * Patient must have measurable disease as defined by having one or more of the following, obtained within 28 days prior to registration/randomization: * ≥ 0.5 g/dL monoclonal protein (M-protein) on serum protein electrophoresis * ≥ 200 mg/24 hrs of monoclonal protein (M-protein) on a 24-hour urine protein electrophoresis * Involved free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (\< 0.26 or \> 1.65) * Exception: patients without measurable disease in the serum or urine, but with bone or soft tissue plasmacytoma(s) ≥ 2 cm or who have bone marrow plasma cells ≥ 30% are eligible on study * NOTE: Urine protein electrophoresis (UPEP) (on a 24 hour collection) is required, no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is ≥ 200 mg/24 hr. Please note that if both serum and urine m-components are present, both must be followed in order to evaluate response * Patient must not be known to be refractory to carfilzomib or pomalidomide * Patient must not have received a prior BCMA therapy * Patient must not be pregnant due to the potential harm to an unborn fetus with the treatment regimens being used * All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration/randomization to rule out pregnancy. Patients must also agree to a second pregnancy test completed within 24 hours prior to the first dose of pomalidomide and teclistamab and agree to ongoing pregnancy testing while on protocol treatment * A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: * 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) * Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 6 months after the last dose of protocol treatment for patients on Arms A, B, and C and for 1 month after the last dose of protocol treatment for patients on Arm D. In addition, all patients must also agree to register to the mandatory Risk Evaluation and Mitigation Strategies (REMS)® program and be willing and able to comply with the requirements of the REMS® program * Patient must agree to not breastfeed while on protocol treatment due to the potential risk for adverse events in nursing infants, and must agree to continue not breastfeeding for an additional 5 months after the last dose of Arm A, B, or C protocol treatment and for an additional 28 days after the last dose of Arm D protocol treatment * Patient must agree to abstain for donating eggs (ova, oocytes) while on study treatment and for 6 months after the last dose of Arm A, B or C protocol treatment * Patient must agree to abstain from donating sperm while on study treatment and for 3 months after the last dose of protocol treatment even if they have had a succ
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What it tests

  • Biospecimen Collection
  • Bone Marrow Aspiration
  • Bone Marrow Biopsy
  • Carfilzomib
  • Computed Tomography
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Where

1 site
City of Hope Comprehensive Cancer Center
Duarte, United States
🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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