Amyloid Light Chain (AL) Amyloidosis
Conditions
Keywords
Amyloid Light Chain Amyloidosis, Newly Diagnosed AL Amyloidosis, Etentamig, ABBV-383, VCd
Brief summary
Amyloid light chain (AL) amyloidosis is a rare disease caused by abnormal plasma cells producing misfolded light chain proteins that deposit in organs, leading to organ dysfunction and failure. The goal of this study is to evaluate the safety and efficacy of etentamig compared to daratumumab plus cyclophosphamide plus bortezomib plus dexamethasone (Dara-CyBorD) in participants with newly diagnosed AL amyloidosis. Etentamig is an investigational drug being developed for the treatment of newly diagnosed AL amyloidosis. This is an open-label study. The study consists of 2 parts: a Safety Run-in where participatns will receive etentamig, and a Randomized Portion with 2 treatment arms where participants will receive etentamig, or Dara-CyBorD. Approximately 370 participants will be enrolled in the study at approximately 130 sites worldwide. Participants will receive injected etentamig, in the Safety Run-in. Participants will receive injected etentamig, or Dara-CyBorD per the local label, in the Randomized Portion of the study. The total study duration is approximately 96 months. There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The effects of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Interventions
DRUGEtentamig
Injection
DRUGDaratumumab
Injection
DRUGCyclophosphamide
Oral
DRUGBortezomib
Injection
DRUGDexamethasone
Oral
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red-stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance. * Evidence of a monoclonal plasma cell proliferative disorder (serum or urine monoclonal protein, abnormal free light-chain ratio, or clonal plasma cells in the bone marrow). * Measurable disease of amyloid light chain (AL) amyloidosis as defined by difference in free light chains (dFLC) \>= 50 mg/L * No history of treatment with anti-amyloidosis therapy. * Presence of an amyloid-related systemic syndrome with at least 1 organ impacted by AL amyloidosis according to International Myeloma Working Group (IMWG) diagnostic criteria. * Considered AL amyloidosis cardiac risk stage 1, 2, or 3a (or 3b \[randomized portion only\]). * Eastern Cooperative Oncology Group performance status \<= 2.
Exclusion criteria
* Known allergic reaction, significant sensitivity, or intolerance to constituents of the study treatments. * Active hepatitis B or hepatitis C infection. * History of other active malignancies within the past 3 years (with specified exceptions).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Randomized Portion: Major Organ Deterioration Progression-Free Survival (MOD-PFS) | Up to Approximately 60 Months | MOD-PFS is defined as the time from the date of randomization to the date of MOD-PFS event or death from any cause, whichever occurs first. MOD-PFS includes: Development of hematologic progressive disease per consensus guidelines or high-risk difference in free light chain (dFLC) progression; Clinical manifestation of cardiac failure (defined as need for cardiac transplant, left ventricular assist device, or intra-aortic balloon pump); Clinical manifestation of renal failure (defined as development of end-stage renal disease needing hemodialysis or renal transplant); Death. MOD-PFS will be assessed by an Independent Review Committee. |
| Number of Participants With Adverse Events | Up to Approximately 96 Months | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. Safety and tolerability assessed through adverse events, laboratory tests, vital signs, physical examinations, and other safety assessments. |
| Randomized Portion: Complete Hematologic Response (HemeCR) Rate | Up to Approximately 60 Months | HemeCR rate is defined as the proportion of subjects with the best overall response of hemeCR as determined by International Amyloidosis Consensus Criteria (IACC) and assessed by the independent review committee (IRC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Run-In and Randomized Portion: Time to Liver Response | Up to Approximately 60 Months | Time from randomization to first achievement of liver response. |
| Safety Run-In and Randomized Portion: Duration of Cardiac Response | Up to Approximately 60 Months | Time from first achievement of cardiac response to cardiac progression. |
| Safety Run-In and Randomized Portion: Duration of Renal Progression | Up to Approximately 60 Months | Time from first achievement of renal response to renal progression. |
| Safety Run-In and Randomized Portion: Duration of Liver Response | Up to Approximately 60 Months | Time from first achievement of liver response to liver progression. |
| Safety Run-In and Randomized Portion: Time to Cardiac Progression | Up to Approximately 60 Months | Time from randomization to first occurrence of cardiac progression. |
| Safety Run-In and Randomized Portion: Time to Renal Progression | Up to Approximately 60 Months | Time from randomization to first occurrence of renal progression. |
| Safety Run-In and Randomized Portion: Time to Liver Progression | Up to Approximately 60 Months | Time from randomization to first occurrence of liver progression. |
| Safety Run-In and Randomized Portion: Maximum Serum Concentration (Cmax) of Etentamig | Up to Approximately 60 Months | Cmax of etentamig. |
| Safety Run-In and Randomized Portion: Time to Maximum Serum Concentration (Tmax) of Etentamig | Up to Approximately 60 Months | Tmax of etentamig. |
| Safety Run-In and Randomized Portion: Area Under the Concentration-Time Curve (AUC) of Etentamig | Up to Approximately 60 Months | AUC of etentamig. |
| Safety Run-In and Randomized Portion: Percentage of Participants With Anti-Drug Antibodies (ADA) | Up to Approximately 60 Months | Immunogenicity assessed through summary of antidrug antibody (ADA) status, ADA titers, and neutralizing antidrug antibodies (NAbs), if NAbs samples are analyzed. |
| Randomized Portion: Change from Baseline in Physical Functioning as Measured by 36-Item Short Form Health Survey Version 2 (SF-36 v2) Physical Component Summary Score | Up to Approximately 60 Months | The SF-36 v2 is a 36-item questionnaire measuring health-related quality of life across eight domains. Higher scores indicate better health status. |
| Randomized Portion: Change from Baseline in Mental Functioning as Measured by SF-36 v2 Mental Component Summary Score | Up to Approximately 60 Months | The SF-36 v2 is a 36-item questionnaire measuring health-related quality of life across eight domains. Higher scores indicate better health status. |
| Randomized Portion: Change from Baseline in Health-Related Quality of Life as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Fatigue Scale Score | Up to Approximately 60 Months | The EORTC QLQ-C30 is a 30-item questionnaire assessing cancer-specific quality of life. Higher scores indicate worse symptoms. |
| Randomized Portion: Change from Baseline in Fatigue as Measured by EORTC QLQ-C30 Fatigue Scale Score | Up to Approximately 60 Months | The EORTC QLQ-C30 is a 30-item questionnaire assessing cancer-specific quality of life. Higher scores indicate worse symptoms. |
| Randomized Portion: Change from Baseline in Disease Symptoms as Measured by Additional EORTC Questionnaire Symptom Scales/Items | Up to Approximately 60 Months | The EORTC questionnaires assess cancer-specific symptoms and quality of life. |
| Safety Run-In: Major Organ Deterioration Progression-Free Survival (MOD-PFS) | Up to Approximately 60 Months | MOD-PFS is defined as the time from the date of randomization to the date of MOD-PFS event or death from any cause, whichever occurs first. MOD-PFS includes: Development of hematologic progressive disease per consensus guidelines or high-risk difference in free light chain (dFLC) progression; Clinical manifestation of cardiac failure (defined as need for cardiac transplant, left ventricular assist device, or intra-aortic balloon pump); Clinical manifestation of renal failure (defined as development of end-stage renal disease needing hemodialysis or renal transplant); Death. |
| Safety Run-In and Randomized Portion: Overall Survival (OS) | Up to Approximately 60 Months | Overall survival defined as the time from randomization to death from any cause. |
| Safety Run-In and Randomized Portion: Percentage of Participants With Hematologic Very Good Partial Response (VGPR) or Better | Up to Approximately 60 Months | Percentage of participants achieving hematologic very good partial response or better based on International Amyloidosis Consensus Criteria. |
| Safety Run-In and Randomized Portion: Cardiac Response Rate | Up to Approximately 60 Months | Percentage of participants achieving cardiac response as assessed per graded criteria. |
| Safety Run-In and Randomized Portion: Renal Response Rate | Up to Approximately 60 Months | Percentage of participants achieving renal response as assessed per the International Amyloidosis Consensus Criteria (IACC) criteria. |
| Safety Run-In and Randomized Portion: Liver Response Rate | Up to Approximately 60 Months | Percentage of participants achieving liver response as assessed per the International Amyloidosis Consensus Criteria (IACC) criteria. |
| Safety Run-In and Randomized Portion: Time to Next Treatment | Up to Approximately 60 Months | Time from randomization to initiation of next anti-AL amyloidosis treatment. |
| Safety Run-In and Randomized Portion: Duration of Complete Hematologic Response | Up to Approximately 60 Months | Duration of complete hematologic response (hemeCR) defined as the time from first documentation of hemeCR to the date of loss of hemeCR. |
| Safety Run-In and Randomized Portion: Time to Complete Hematologic Response | Up to Approximately 60 Months | Time from randomization to first documentation of complete hematologic response (hemeCR) as determined by International Amyloidosis Criteria Committee. |
| Randomized Portion: Time to Cardiac Response | Up to Approximately 60 Months | Time from randomization to first achievement of cardiac response. |
| Safety Run-In and Randomized Portion: Time to Renal Response | Up to Approximately 60 Months | Time from randomization to first achievement of renal response. |
Contacts
CONTACTABBVIE CALL CENTER
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed