Venetoclax, Daratumumab, and Dexamethasone for Systemic Light-Chain Amyloidosis With Translocation (11;14) (ALTITUDE)

Sponsor
Alfred Chung, MD
Study ID
NCT05486481
Phase
PHASE1/PHASE2
Status
Withdrawn

Conditions

  • AL Amyloidosis
  • Light Chain (AL) Amyloidosis
  • Systemic Light Chain Disease

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax — DRUG
    Given orally (PO)
  • Dexamethasone — DRUG
    Given PO
  • Daratumumab — DRUG
    Given Subcutaneously (SC)
  • Cyclin D1 gene (CCDN1) /immunoglobulin heavy chain (IGH) fluorescence in situ hybridization (FISH) assay — DEVICE
    Lab test

Study Details

This phase I/II trial tests the safety, side effects, and best dose of venetoclax, daratumumab, and dexamethasone for the treatment of systemic light-chain amyloidosis in patients with a deoxyribonucleic acid (DNA) abnormality called a translocation involving chromosomes 11 and 14, or "t(11;14)". Venetoclax works by attaching to a protein called Bcl-2, in order to kill cancer cells. Daratumumab works by binding to a target on the surface of cancer cells called Cluster of differentiation 38 (CD38). When daratumumab binds to CD38, it enables the immune system to find the cancer cell and kill it. Dexamethasone is a type of drug called a corticosteroid. A corticosteroid is a drug made of artificial steroid hormones, that are used to treat symptoms such as inflammation (swelling and irritation to a part of the body). The combination of these medications may more effectively treat patients with systemic light-chain amyloidosis and t(11;14).

Key Dates

Start date
Jan 8, 2024
Status verified
Mar 2025
Primary completion
Dec 31, 2028
Completion
Dec 31, 2028

Study Design

Enrollment
0 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase I (venetoclax, dexamethasone, daratumumab)
    All participants receive 400 mg venetoclax once a day (QD) on days 1-28 of each cycle. Depending on the number of DLTs reported for this dose-level, participants may also receive dexamethasone on days 1, 8, 15, and 22 of each cycle with or without daratumumab on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, then on day 1 of cycles thereafter. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Experimental: Phase II (venetoclax, dexamethasone, daratumumab)
    Participants will receive the RP2D of venetoclax QD on days 1-28 of each cycle, dexamethasone on days 1, 8, 15, and 22 of each cycle, and daratumumab on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, then on day 1 of cycles thereafter. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity

Primary Outcome Measure

Proportion of participants with reported dose limiting toxicities (Phase 1) [ Time Frame: Up to 1 cycle (1 cycle is equal to 28 days) ]

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