A Phase III, Multicentre Study to Evaluate Consolidation Treatment With AZD0120 Compared With ASCT, in Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible (DURGA-6).

Официальное название

A Phase III, Open-label, Multicentre, Randomised Study Comparing Consolidation Treatment With AZD0120, an Autologous Dual Targeting Chimeric Antigen Receptor T-cell (CAR-T) Therapy Directed Against BCMA and CD19, Versus Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible (TE NDMM) (DURGA-6)

Обзор

The purpose of this study is to measure the efficacy of AZD0120 compared with ASCT in terms of progression-free survival (PFS) according to the International Myeloma Working Group (IMWG) criteria 2016, and MRD negative complete response (CR) rate at 9 months as assessed by Blinded Independent Central Review (BICR), in participants with TE NDMM. Study details include: * The study duration is estimated to be up to 13 years from the date the first participant is randomised. * For participants in Arm A (AZD0120), the total duration of participant follow-up will be 15 years (including a Long Term Follow-up study) after the last participant has received the AZD0120 infusion. * The treatment duration will be:- Arm A (AZD0120): lymphodepletion over 3 days, a single-day infusion of AZD0120, followed by a maximum of 2 years lenalidomide monotherapy maintenance treatment. * Arm B (ASCT): conditioning therapy over 24 to 48 hours, ASCT, followed by a maximum of 2 years lenalidomide monotherapy maintenance treatment. Disclosure Statement: This is an open-label, randomised study with 2 treatment arms.

Вмешательства

• Биопрепарат AZD0120
  Arm A: AZD0120 - autologous BCMA/CD19 dual-targeting CAR-T cells. Participants will receive lymphodepletion conditioning (cyclophosphamide and fludarabine) followed by AZD0120 CAR-T cell infusion.
• Препарат Cyclophosphamide
  Arm A: Cyclophosphamide will be given intravenously as lymphodepletion conditioning.
• Препарат Fludarabine
  Arm A: Fludarabine will be given intravenously as lymphodepletion conditioning.
• Препарат Melphalan (part of ASCT)
  Arm B - Autologous stem cell transplant: High-dose melphalan will be given over 1-2 days, followed by autologous stem cell rescue.
• Препарат Lenalidomide
  Arm A and Arm B: Lenalidomide maintenance treatment will be started in both Arm A and Arm B after AZD0120 therapy or ASCT, respectively. Lenalidomide maintenance on study will be continued up to 2 years.

Первичные конечные точки

• Progression-Free Survival (PFS) [Срок оценки: Up to approximately 13 years.]
• Minimal Residual Disease (MRD) negative Complete Response Rate (CRR) [Срок оценки: Up to approximately 13 years.]

Вторичные конечные точки (6)

• Secondary: Overall Survival (OS) [Срок оценки: Up to approximately 13 years.]
• Secondary: Complete Response Rate (CRR) [Срок оценки: Up to approximately 13 years.]
• Secondary: Overall Response Rate (ORR) [Срок оценки: Up to approximately 13 years.]
• Secondary: Duration of Response (DoR) [Срок оценки: Up to approximately 13 years.]
• Other secondary: Time to Response (TTR) [Срок оценки: Up to approximately 13 years.]
• Safety - Adverse Events [Срок оценки: Up to approximately 13 years.]

Критерии участия

Критерии включения

• ≥18 years of age.
• Documented diagnosis of NDMM according to IMWG diagnostic criteria.
• Documented measurable disease at diagnosis (serum M-protein ≥ 1.0 g/dL, urine M-protein 200 mg/24 hour, or serum Ig FLC 10 mg/dL (100 mg/L) and abnormal serum Ig kappa lambda FLC ratio)
• Must have completed 4 to 6 cycles of induction therapy with any of the following approved regimens: anti-CD38+VRd, DVTd, DRd or VRd
• Participant must have at least SD or better per IMWG response criteria (2016) after completion of induction, and prior to randomisation.
• ECOG performance status score of 0 or 1.
• Eligible for treatment with high-dose melphalan (200 mg/m²) followed by ASCT.
• Adequate organ and bone marrow function.

Критерии исключения

• Known active, or prior history of CNS involvement or exhibits clinical signs of meningeal involvement of MM.
• Primary amyloidosis, active plasma cell leukaemia (at diagnosis and/or at time of screening), Waldenstrom macroglobulinemia or POEMS syndrome.
• Significant neurological or psychiatric condition
• Significant medical condition that places the participant at an unacceptable risk for treatment-related complications
• Participants who required the introduction of an additional agent therapy due to inadequate response.
• Prior T-cell engager therapy directed at any target.
• Prior CAR-T and/or CAR-NK cell therapy directed at any target for any indications
• Prior any therapy that is targeted to BCMA and CD19.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• Research Site — Tampa
• Research Site — Atlanta
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• Research Site — Chicago
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• … и ещё 2 центра

Германия · 8 центров

• Research Site — Berlin
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Испания · 7 центров

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Австралия · 6 центров

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Италия · 6 центров

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Польша · 6 центров

• Research Site — Gdansk
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Франция · 5 центров

• Research Site — Lille
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South Korea · 4 центра

• Research Site — Seoul
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Бразилия · 3 центра

• Research Site — Salvador
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Дания · 3 центра

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Сингапур · 2 центра

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Великобритания · 2 центра

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Канада · 1 центр

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Норвегия · 1 центр

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Тайвань · 1 центр

• Research Site — Taipei

Идентификаторы

NCT: NCT07735637 · D8316C00001 · AZD0120

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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