Trials / Withdrawn
WithdrawnNCT05486481
Venetoclax, Daratumumab, and Dexamethasone for Systemic Light-Chain Amyloidosis With Translocation (11;14) (ALTITUDE)
A Multicenter Phase 1/2 Study of Venetoclax/Daratumumab/Dexamethasone for Previously Treated Systemic Light-Chain Amyloidosis With Translocation (11;14)
- Status
- Withdrawn
- Phase
- Phase 1 / Phase 2
- Study type
- Interventional
- Enrollment
- 0 (actual)
- Sponsor
- Alfred Chung, MD · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
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).
Detailed description
PRIMARY OBJECTIVES: I. To determine the maximum-tolerated dose (MTD)/ the recommended phase 2 dose (RP2D) of venetoclax (VEN) with or without daratumumab subcutaneous (DARA SC) and dexamethasone (DEX), in previously treated light chain (AL) amyloidosis (PTAL) participants with t(11;14). (Phase I). II. To evaluate the efficacy of the combination VEN/DARA SC and DEX as measured by Complete Hematologic Response (CHR rate) in PTAL participants with t(11;14). (Phase II) SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of VEN/DARA SC, and DEX in the treatment of PTAL participants with t(11;14). (Phase I) II. To evaluate the efficacy of VEN/DARA SC and DEX in the treatment of PTAL participants with t(11;14) as measured by overall hematologic response rate (ORR), progression free survival (PFS), overall survival (OS), organ response rate (orRR), major organ deterioration PFS (MOD-PFS), time to complete response (TTCR), duration of response (DOR), and time to new treatment (TTNT). To evaluate safety of VEN/DARA SC and DEX in the treatment of PTAL participants with t(11;14). (Phase II) IV. To evaluate the death rate, therapy-related death rate, infection rate, and cardiac event rate, in the VEN/DARA SC and DEX arm and the DARA SC and DEX arm. (Phase II). EXPLORATORY OBJECTIVES: I. To evaluate the feasibility of performing M protein detection by MALDI TOF mass spectrometry on the EXENT® system on serum and urine participant-samples collected by each site during the first 6 months of the study. II. To evaluate the agreement between MALDI TOF mass spectrometry results by the EXENT® system and standard serologic and urine measures of disease after the enrollment for both phase 1 and 2 has been complete. III. To evaluate the complete response (CR) rate, ORR, PFS, MOD-PFS, OS, OrRR, TTCR, TTNT and DOR separated by participants who are minimal residual disease (MRD) negative versus positive by EXENT®. IV. To evaluate the CR rate, overall hematologic response rate (ORR), progression-free survival (PFS), major organ deterioration PFS (MOD-PFS), overall survival (OS), organ response rate (OrRR), time to complete response (TTCR), time to next treatment (TTNT) and duration of response (DOR) and relationship to light-chain glycosylation patterns over time by EXENT®. OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study. If dose level 3 (VEN/DARA SC and DEX) is not the recommended phase 2 doses/maximum tolerated dose in phase 1, the study will not open to phase 2. PHASE I: All participants receive venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle. Depending on dose-level assignment, participants may also receive dexamethasone PO on days 1, 8, 15, and 22 of each cycle with or without daratumumab SC 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. PHASE II: Participants receive venetoclax PO QD on days 1-28 of each cycle, dexamethasone PO on days 1, 8, 15, and 22 of each cycle, and daratumumab SC 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. After completion of study treatment, participants are followed up at 30 days and then every 3 months until the last participant on the study completes 2 years of treatment.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Venetoclax | Given orally (PO) |
| DRUG | Dexamethasone | Given PO |
| DRUG | Daratumumab | Given Subcutaneously (SC) |
| DEVICE | Cyclin D1 gene (CCDN1) /immunoglobulin heavy chain (IGH) fluorescence in situ hybridization (FISH) assay | Lab test |
Timeline
- Start date
- 2024-01-08
- Primary completion
- 2028-12-31
- Completion
- 2028-12-31
- First posted
- 2022-08-03
- Last updated
- 2025-03-06
Regulatory
- FDA-regulated drug study
- FDA-regulated device study
Source: ClinicalTrials.gov record NCT05486481. Inclusion in this directory is not an endorsement.