Elranatamab in Relapsed/Refractory Multiple Myeloma

Официальное название

Phase II MRD-Adapted Study of Elranatamab in Relapsed/Refractory

Обзор

This study evaluates the efficacy of elranatamab alone in patients with relapsed and/or refractory Multiple myeloma who has previously received 1 to 3 combinations of treatment.

Подробное описание

Phase II study of elranatamab in patients with relapsed/refractory multiple myeloma who has received 1 to 3 prior lines of therapy. Patients may enter treatment-free observation period if they have a sustained MRD negative response for greater than 12 months.

Вмешательства

• Препарат Elranatamab
  Subcutaneous injection of elranatamab. If patient achieves MRD negative remission, patient would enter treatment-free observation period with MRD monitoring.

Первичные конечные точки

• MRD negativity rate as best response [Срок оценки: 1 year of starting treatment]

Вторичные конечные точки (7)

• Sustained MRD negativity rate at 10^-5 [Срок оценки: Through study completion, up to 5 years]
• Overall response rate [Срок оценки: Within 1 year of treatment]
• Complete response rate [Срок оценки: Within 1 year of treatment]
• Progression free survival [Срок оценки: Through study completion, up to 5 years]
• Duration of response [Срок оценки: Through study completion, up to 5 years]
• Safety (cytokine release syndrome, neurotoxicity, treatment-related adverse events) [Срок оценки: Through study completion, on average 4 weeks (cytokine release syndrome, neurotoxicity); Through study completion, up to 5 years (treatment-related adverse events as assessed by CTCAE v5.0 )]
• Quality of life (questionnaire and by EORTC QLQ-MY20 questionnaire) [Срок оценки: Through study completion, up to 5 years]

Критерии участия

Критерии включения

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Prior diagnosis of relapsed/refractory MM and have received 1 to 3 prior lines of therapy as defined by the IMWG criteria (Rajkumar et al., 2014) including anti-CD38 monoclonal antibody, proteosome inhibitor (PI), and immunomodulatory drug (IMiD), and BCMA-directed chimeric antigen receptor T-cell (CAR T-cell) therapy

• Refractory is defined as having disease progression while on therapy or within 60 days of last dose in any line, regardless of response.
• If participant has not received BCMA-directed CAR T-cell therapy, must be ineligible for CAR T-cell therapy or deferred such treatment by participant
• Aged greater or equal to 18 years
• Measurable disease as defined by any of the following:

• Serum M-protein level ≥ 0.5 g/dL by serum protein electrophoresis (SPEP), or
• Urine M-protein ≥ 200mg/24 hours by urine protein electrophoresis (UPEP), or
• Involved serum free light chain ≥ 10 mg/dL (≥100mg/L) AND an abnormal serum free light chain ratio in patients without measurable disease in the serum or urine
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Adequate hematological function defined as

• Absolute neutrophil count (ANC) ≥1,000/mm3 (G-CSF not permitted for at least 1 week prior to the first dose of elranatamab)
• Hemoglobin ≥8.0 g/dL (transfusion support is permitted if completed at least 1 week prior to planned start of dosing)
• Platelet count ≥75,000/mm3 or ≥50,000/mm3 if >50% involvement with plasma cells in the screening bone marrow (transfusion support is permitted if completed at least 1 week prior to planned start of dosing)
• Adequate renal function with estimated creatinine clearance (CrCl) ≥30 mL/min as calculated using Cockcroft-Gault equation.
• Adequate liver function defined as

• Aspartate and alanine aminotransferase (AST and ALT) ≤2.5 x upper limit of normal (ULN); ≤5.0 x ULN if there is liver involvement by the tumor.
• Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN in case of bone metastasis).
• Total bilirubin ≤2.0 mg/dL, except in patients with Gilbert Syndrome who must have a total bilirubin less than 3.0 mg/dL.
• Able to receive outpatient treatment of elranatamab by meeting the following criteria:

• Lives within 30minutes from the site of medication administration
• Reliable caregiver present, who is able to watch participant continuously for at least until 48 hours after administration of first full treatment dose
• No history of grade 3-4 CRS or grade 3-4 ICANS from other immune effector cell or bispecific antibody therapies
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1
• Serum pregnancy test (for females of childbearing potential) negative at screening.

a. Female patients of non-childbearing potential must meet at least 1 of the following criteria: i. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state.

ii. Have undergone a documented hysterectomy and/or bilateral oophorectomy. iii. Have medically confirmed ovarian failure. b. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.

• Agreement to adhere to Lifestyle Considerations (see section 5.3 and Appendix 2) throughout study duration

Критерии исключения

• Subjects with smoldering multiple myeloma, IgM multiple myeloma, Waldenstrom's macroglobulinemia, amyloidosis, POEMS syndrome, and primary and secondary plasma cell leukemia, defined as circulating plasma cells ≥ 5%
• Extramedullary relapse who does not meet criteria for measurable disease as above
• Active malignancy other than Multiple Myeloma requiring treatment in the past 3 years, with the exception of successfully treated non-metastatic squamous or basal skin carcinoma
• Known CNS involvement by multiple myeloma
• Active, uncontrolled autoimmune disorders
• Active uncontrolled infection. Active infections must be resolved and/or controlled at least 14 days prior to enrollment.
• Radiation therapy within 2 weeks prior to study entry (bone lesions requiring radiation may be treated with limited \[ie, ≤25% of bone marrow in field\] radiation therapy during this period).
• Last systemic treatment within 2 weeks or 5 half lives, whichever is shorter. Subjects can receive a maximum of 160mg of dexamethasone or equivalent during screening, but at least 7 days prior to start of therapy.
• Last radiation treatment to multiple sites within 2 weeks and single site within 1 week
• History of autologous stem cell transplant within 100 days prior to study enrollment.
• History of allogeneic transplant within 1 year prior to study enrollment or active graft versus host disease.
• On immunosuppressive therapy for concurrent comorbid conditions
• Other major uncontrolled medical comorbidities that may put patients at risk of serious adverse event with treatment with study medication.
• Clinically significant, uncontrolled cardiac disease
• Grade ≥2 peripheral sensory or motor neuropathy
• History of Guillan-Barre syndrome
• Other surgical (including major surgery within 14 days prior to enrollment) or psychiatric conditions including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
• Pregnancy or lactation
• Known or suspected hypersensitivity to the study intervention or any of its excipients.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of California San Diego — La Jolla

Идентификаторы

NCT: NCT06711705 · 810312

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗