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Testing the Investigational Medication Combination of Daratumumab and Teclistamab Compared to the Usual Treatment (Daratumumab, Pomalidomide, Dexamethasone or Daratumumab, Carfilzomib, Dexamethasone) for Patients With High-risk Multiple Myeloma Refractory or in First Relapse

RecruitingPhase 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 II trial compares the effect of the combination of daratumumab-hyaluronidase (daratumumab) and teclistamab to the usual treatment of daratumumab, pomalidomide, dexamethasone or daratumumab, carfilzomib and dexamethasone in treating patients with multiple myeloma that has not responded to previous treatment (refractory) or that has come back after a period of improvement (relapsed). Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Teclistamab is a bispecific antibody that can bind to two different antigens at the same time. Teclistamab binds to B-cell maturation antigen, a protein found on some B-cells and myeloma cells, and CD3 on T-cells (a type of white blood c

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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 (PS) of 0-2 (PS 3 allowed if secondary to pain) * Patient must have an identifiable dominant sequence (clonotype) established based on Adaptive Biotechnologies clonoSEQ® assay * Patient must have received only one prior line of therapy * One prior line of systemic therapy is defined as 1 or more cycles of single agent or combination therapy, as well as a series of treatment regimens administered in a sequential manner (e.g., lenalidomide, bortezomib and dexamethasone induction therapy for 4 cycles followed by autologous stem cell transplantation and then lenalidomide +/- proteasome inhibitor or anti-CD38 monoclonal antibody \[mAb\] maintenance therapy would be considered 1 line of prior therapy) * NOTE: Autologous stem cell transplant is allowed provided the stem cell infusion was \> 90 days prior to randomization. Allogeneic stem cell transplantation (SCT) patients are ineligible * Patient must be diagnosed with relapsed or refractory (RR) multiple myeloma, as defined by disease progression, either an increase in serum or urine M protein of any level, or other evidence of progression biochemical or clinical as specified in the IMWG progression criteria (including disease which becomes non-responsive or progressive on therapy or within 60 days of the last treatment in patients who had achieved a partial response or better on prior therapy) * Patient must be daratumumab-hyaluronidase (or isatuximab) naïve or daratumumab-hyaluronidase (or isatuximab) sensitive and \> 180 days from their last dose of daratumumab-hyaluronidase (or isatuximab) at the time of randomization * Patient must have high-risk multiple myeloma (HR-MM) as defined by one of the following either at diagnosis or at refractory status or at first relapse: * Evidence of deletion 17p by fluorescence in situ hybridization (FISH) testing on bone marrow * Evidence of t(4;14) by FISH testing on bone marrow * Evidence of t(14;16) by FISH testing on bone marrow * Evidence of t(14;20) by FISH testing on bone marrow * Evidence of chromosome 1 abnormalities either gain/amp 1q or deletion 1p by FISH testing on bone marrow OR * Evidence of non-hyperdiploid karyotype OR * Revised International Staging System (R-ISS) stage III beta2 microglobulin ≥ 5.5 mg/L and serum lactate dehydrogenase (LDH) \> institutional upper limit of normal (ULN) OR * Patient in first relapse and ≤ 24 months from the start of induction for both allogeneic stem cell transplantation (ASCT) eligible or ASCT ineligible patients (regardless of FISH, cytogenetic or RISS stage) * Patient must have measurable disease as defined by having one or more of the following, obtained within 28 days prior to randomization: * Serum M protein ≥ 0.5 g/dL (≥ 5 g/L) * Urine M protein ≥ 200 mg/24 hours * Serum free light chain (FLC) assay: Involved free light chain level ≥ 10 mg/dL (≥ 100 mg/L) provided serum FLC ratio is abnormal (\< 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 * Patient must have serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and serum FLC assays along with bone marrow biopsy or aspirate performed within 28 days prior to randomization * NOTE: 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. If both serum and urine M-components are measurable, both must be followed in order to confirm response * NOTE: The serum free light chain test is required to be done at each cycle * Patient must not have any known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or investigator's brochure), or known sensitivity to mammalian-derived products * Patients who have received prior systemic therapy for myeloma, including experimental therapy and steroids must have recovered from clinically significant adverse events prior to randomization * Patient may not be on steroids (prednisone \> 40mg/day or equivalent) at the time of randomization * Patient may have received prior palliative and/or localized radiation, provided that it is completed by the time of randomization * Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible * Absolute neutrophil count (ANC) ≥ 1,000/uL (=\< 28 days prior to protocol randomization) * Untransfused platelet count ≥ 50,000/uL (for patients with ≥ 50% plasma cells in the marrow) and untransfused platelet count \> 75,000/uL (for patients with \< 50% plasma cells in the marrow) (=\< 28 days prior to protocol randomization) * Untransfused hemoglobin ≥ 8.0 g/dL (=\< 28 days prior to protocol randomization) * Total bilirubin ≤ 1.5 x institutional ULN (upper limit of normal) (=\< 28 days prior to protocol randomization) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 × institutional ULN (=\< 28 days prior to protocol randomization) * Calculated creatinine clearance \> 30 mL/min (=\< 28 days prior to protocol randomization) * NOTE: Cockcroft-Gault equation should be used to calculate creatinine clearance * Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used * All patients of childbearing potenti
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What it tests

  • Biospecimen Collection
  • Bone Marrow Biopsy
  • Carfilzomib
  • Computed Tomography
  • Daratumumab and Recombinant Human Hyaluronidase
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Where

31 sites
Kootenai Health - Coeur d'Alene
Coeur d'Alene, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, United States
Illinois CancerCare-Bloomington
Bloomington, United States
Illinois CancerCare-Canton
Canton, United States
Illinois CancerCare-Carthage
Carthage, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, United States
Decatur Memorial Hospital
Decatur, United States

…and 23 more on ClinicalTrials.gov.

🤝 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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