A Phase 2, Multicohort Study of Daratumumab-Based Therapies in Participants with Amyloid Light Chain (AL) Amyloidosis

Phase 1

• Conditions: Amyloid Light Chain Amyloidosis; MedDRA version: 23.0Level: LLTClassification code: 10083938Term: Amyloid light-chain amyloidosis Class: 10021428; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: CTIS2023-507069-25-00
• Lead Sponsor: Janssen - Cilag International

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-10-27
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

=18 years of age, A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for a period of least 1 year after the last dose of cyclophosphamide or 100 days after discontinuation of daratumumab, whichever is longer., A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of cyclophosphamide or 100 days after discontinuation of daratumumab, whichever is longer., Signed an informed consent form (ICF)., Cohort 2 only: self-identified racial and ethnic minorities, including Black or African American., New diagnosis of systemic AL amyloidosis based on both: (a) tissue deposition of amyloid in any organ other than bone marrow and (b) an underlying clonal plasma cell disorder as demonstrated by any one of the following: • Clonal plasma cells in the bone marrow • Monoclonal gammopathy in the serum or urine • Abnormal free light chain ratio, Measurable disease at screening defined by one of the following: • difference between iFLC and uninvolved FLC (dFLC) =40mg/L per central laboratory • serum M-protein =0.5 g/dL, Cohort 1: Cardiac involvement (AL amyloidosis Mayo Cardiac Stage II and Stage IIIa; see Appendix 6) with or without other organ(s) involved Cohort 2: One or more organs impacted by systemic AL amyloidosis according to consensus guidelines, Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2, Pre-treatment clinical laboratory values meeting the following criteria during the Screening Phase: • Hemoglobin =8.0 g/dL (=5 mmol/L); red blood cell transfusion allowed until 7 days before randomization/enrollment • Platelets =50×10^9/L; platelet transfusions are allowed until 7 days before randomization/enrollment • Absolute Neutrophil count =1.0×10^9/L • Aspartate aminotransferase and alanine aminotransferase =2.5× ULN • Total bilirubin =1.5 × ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin =2×ULN is required) • Estimated glomerular filtration rate =20 mL/min/1.73 m^2, A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study, A female participant must be either of the following: a. Not of childbearing potential b. Of childbearing potential and practicing true abstinence or have a sole partner who is vasectomized or practicing at least 1 highly effective user independent method of contraception. Contraception must begin 4 weeks prior to dosing and continue for 1 year after discontinuation of cyclophosphamide or 100 days after discontinuation of daratumumab, whichever is longer., A male participant must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after discontinuation of cyclophosphamide or 100 days after discontinuation of daratumumab, whichever is longer. His female partner, if of childbearing potential, must also be practicing a highly effective method of contraception. If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not re

Exclusion Criteria

Prior therapy for systemic AL amyloidosis or multiple myeloma including medications that target CD38, with the exception of 160 mg dexamethasone or equivalent corticosteroid maximum exposure prior to randomization/enrollment., Pregnant or breastfeeding or planning to become pregnant while enrolled in this study or within 1 year after discontinuation of cyclophosphamide or 100 days after the last dose of daratumumab, whichever is longer, Plans to father a child while enrolled in this study or within 6 months after discontinuation of cyclophosphamide or 100 days after the last dose of daratumumab, whichever is longer., Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal, Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification, Participant is known to be positive for human immunodeficiency virus (HIV), with 1 or more of the following: • Not receiving highly active antiretroviral therapy (ART) • Had a change in ART within 6 months of the start of screening • Receiving ART that may interfere with study treatment (consult Sponsor for review of medication prior to enrollment) • CD4 count <350 at screening • Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of start of screening • Not agreeing to start ART and be on ART >4 weeks plus having HIV viral load <400 copies/mL at end of 4-week period (to ensure ART is tolerated and HIV controlled), Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HbsAg]). (Conditions for resolved infection are specified in protocol), Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)., Any serious underlying medical or psychiatric condition or disease, that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study, such as: • Evidence of serious active viral or bacterial infection, requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection. • Active autoimmune disease or a history of autoimmune disease within 2 years. EXCEPTION: Participants with vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing are eligible regardless of when these conditions were diagnosed. • Disabling psychiatric conditions (eg, alcohol or drug abuse), severe dementia, or altered mental status, Any other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the study site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments, Major surgical procedure within 2 weeks before randomization/enrollment or has not fully recovered from an earlier surgical procedure, or has major surgical procedure planned during the time the participant is expected to participate in the study., Previous or current diagnosis of symptomatic multiple myeloma per International Myeloma Working Group (IMWG) Criteria., Any form of non-AL amyloidosis, including ATTR amyloidosis., Participant received

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified