Multiple Myeloma
Conditions
Keywords
Multiple myeloma, BCMA, CD19, CAR-T
Brief summary
This is an interventional, modular, open-label, multicenter study to primarily evaluate the safety and tolerability of AZD0120 in adult participants with multiple myeloma (MM).
Detailed description
This modular study aims to evaluate the safety, tolerability, cellular kinetics, pharmacodynamic effect, immunogenicity, and preliminary efficacy of AZD0120 in subjects with newly diagnosed or early relapsed or primary refractory multiple myeloma. Module 1 consists of early line MM (including newly diagnosed MM and early relapsed or primary refractory MM) with AZD0120 (for newly diagnosed multiple myeloma (NDMM), the intervention is with AZD0120 ± maintenance). Module 2 consists of NDMM with AZD0120 ± maintenance.
Interventions
BIOLOGICALAZD0120
AZD0120 is a BCMA/CD19 dual CAR T cell product under investigation for early-line treatment in subjects with multiple myeloma
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
AZD0120 will be administrated in one infusion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age: * Males and females ≥18 years of age at the time of consent Type of Participant and Disease Characteristics: * Participant must have documented diagnosis of MM per IMWG diagnostic criteria * ECOG performance status of 0 or 1. * Adequate organ and bone marrow function. For NDMM participants: * Participants on Module 1: Newly diagnosed multiple myeloma (NDMM) without prior anti- myeloma therapy (no more than 2 cycles of induction therapy before enrollment are acceptable) * For participants on Module 2: Newly diagnosed MM with a minimum of 4 cycles and a maximum of 6 cycles of induction therapy completed prior to screening * Classified as high-risk MM For Early Relapsed or Primary Refractory MM (1 or 2 prior lines of therapy) participants: * Have received and failed 1 or 2 lines of anti-myeloma therapy * Have received a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) as part of their previous therapy * Have documented evidence of progressive disease based on investigator's determination of response by the IMWG criteria within 1 year of starting treatment, or on or within 6 months of completing treatment of the subject's last line of anti-myeloma therapy, or have confirmed progressive disease within 6 months prior to screening and who are subsequently determined to be refractory or non-responsive to their most recent anti-myeloma treatment regimen General
Exclusion criteria
* Have received prior treatment with CAR T therapy directed at any target * Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma * Active or history of plasma cell leukemia at the time of screening * Seropositive for human immunodeficiency virus (HIV) * Active Hepatitis B infection * Active Hepatitis C infection * Serious underlying medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) | 2 years | Incidence and severity of adverse events (AEs) |
| Serious Adverse Events (SAEs) | 2 years | Incidence and severity of serious adverse events (SAEs) |
| Dose Limiting Toxicities (DLT) | 28 days | Incidence of dose limiting toxicities events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic - AUC0-28d | 0-28 Days | Area under the concentration time-curve of AZD0120 level |
| Pharmacokinetic AUC0-3M | 0 - 3 Months | Area under the concentration time-curve of AZD0120 level |
| Pharmacokinetic AUClast | 2 years | Area under the concentration time-curve of AZD0120 level |
| Pharmacokinetic - Cmax | 2 years | Maximum AZD0120 level |
| Pharmacokinetic - Tmax | 2 years | Time to reach Maximum AZD0120 level |
| Pharmacokinetic - Clast | 2 years | Observed concentration of AZD0120 at last quantifiable concentration |
| Pharmacokinetic - Tlast | 2 years | Time to last quantifiable concentration of AZD0120 level |
| Pharmacokinetic - Quantification of CAR transgene levels | 2 years | Determination of transgene level |
| Efficacy - Objective Response Rate (ORR) | 2 years | Defined as proportion of participants who achieve an overall response of PR or better according to the IMWG 2016 criteria |
| Efficacy - Complete Response Rate (CRR) | 2 years | Defined as proportion of participants who achieve a CR/sCR response according to the to the IMWG 2016 criteria |
| Efficacy - Minimal Residual Disease (MRD) Negative CR Rate at 9 Months (± 3 months) | 9 months | Defined as the proportion of participants with CR/sCR and MRD negative status at 9 months (± 3 months) following AZD0120 infusion |
| Efficacy - Sustained Minimal Residual Disease (MRD) Negative CR Rate | 2 years | Defined as the proportion of participants who achieve CR/sCR and maintain MRD negative status for at least 12 months with no positive MRD detected during that period |
| Efficacy - Duration of Response (DOR) | 2 years | Defined as the time from first documented confirmed response until date of documented PD per IMWG 2016 criteria or death due to any cause, whichever occurs first |
| Efficacy - Time to Response (TTR) | 2 years | Defined as the time from infusion until the date of first documented objective response, as assessed per IMWG 2016 criteria |
| Humoral Immunogenicity | 2 years | Prevalence and incidence ADAs against AZD0120 and the impact on PK, efficacy, and safety, as data allow |
| Module 2 Adverse Events (AEs) Maintenance | 2 years | Incidence and severity of AEs for maintenance following AZD0120 infusion in participants with NDMM |
| Module 2 Serious Adverse Events (SAEs) Maintenance | 2 years | Incidence and severity of SAEs for maintenance following AZD0120 infusion in participants with NDMM |
Countries
United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed