NCT04131309

A Study of Daratumumab Monotherapy in Previously Untreated Patients With Stage 3B Light Chain (AL) Amyloidosis

Phase 2 Study of Daratumumab Monotherapy in Previously Untreated Patients With Stage 3B Light Chain (AL) Amyloidosis

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Stichting European Myeloma Network · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, multicenter, Phase 2 study in subjects with newly diagnosed stage 3B light chain (AL) amyloidosis.

Detailed description

The current study aims to investigate daratumumab as a monotherapy in patients with stage 3B AL amyloidosis who have not received prior therapy. Approximately 40 subjects will receive primary therapy with daratumumab. Subject participation will include a Screening Phase, a Treatment Phase, a Post-Treatment Observation Phase, and a Long-term Follow-up Phase. A safety run-in will be conducted in 6 subjects treated with daratumumab for at least 1 cycle to establish safety of daratumumab in patients with stage 3B AL amyloidosis. Dosing of these 6 subjects will be staggered so that no subject will receive their first dose sooner than 48 hours after the previously enrolled subject. Safety evaluation will be performed by a Data Safety Monitoring Board (DSMB) after at least 1 cycle is completed for all 6 subjects. If no safety signal is observed, the enrollment of the rest of the patients will begin. In Protocol Version 1.0, subjects receive daratumumab IV at a dose of 16 mg/kg. As of Protocol Amendment 1, all new subjects are dosed subcutaneously with daratumumab co-formulated with recombinant human hyaluronidase rHuPH20 (daratumumab SC). Subjects who already began treatment with daratumumab IV (i.e., prior to Amendment 1) switch to daratumumab SC on the next administration date according to the protocol schedule. Subjects receive daratumumab IV at a dose of 16 mg/kg and daratumumab SC at a fixed dose of 1800 mg for the first 8 weeks (Cycles 1 and 2) of treatment and then every 2 weeks for 4 cycles (Cycles 3 to 6) and then every 4 weeks until progression of disease (according to MOD-PFS), unacceptable toxicity or subsequent therapy, for a maximum of 2 years in total. All treatment cycles are 4 weeks (28 days) in length. Subjects who will not achieve either a hematologic VGPR or better, OR a hematologic PR with a major organ response by Cycle 4 Day 1 may receive at Investigator's discretion, in addition to daratumumab, bortezomib (1.3 mg/m2 weekly for a maximum of 6 cycles) and low dose dexamethasone (total maximum weekly dose of 20mg).

Conditions

• Light Chain (AL) Amyloidosis, Stage 3B

Interventions

Type	Name	Description
DRUG	Daratumumab	As of Protocol Amendment 1, all new subjects are dosed with daratumumab subcutaneous injection (SC) co-formulated with recombinant human hyaluronidase rHuPH20. Subjects who already began treatment with daratumumab intravenous (IV) infusion (i.e., prior to Am 1) switch to SC on the next administration date according to the protocol schedule. Subjects receive daratumumab IV at a dose of 16 mg/kg and daratumumab SC at a fixed dose of 1800 mg for the first 8 weeks (Cycles 1 and 2) of treatment and then every 2 weeks for 4 cycles (Cycles 3 to 6) and then every 4 weeks until progression of disease (according to MOD-PFS), unacceptable toxicity or subsequent therapy, for a maximum of 2 years in total. All treatment cycles are 4 weeks (28 days) in length.
DRUG	Bortezomib Injection	Subjects who do not achieve either a hematologic VGPR or better, OR a hematologic PR with a major organ response by Cycle 4 Day 1 may receive at Investigator's discretion, in addition to daratumumab, bortezomib at a dose of 1.3 mg/m2 weekly for a maximum of 6 cycles as a subcutaneous injection
DRUG	Dexamethasone oral tablet	Subjects who do not achieve either a hematologic VGPR or better, OR a hematologic PR with a major organ response by Cycle 4 Day 1 may receive at Investigator's discretion, in addition to daratumumab low dose dexamethasone at a maximum total dose of 20 mg weekly.

Timeline

• Start date: 2019-09-23
• Primary completion: 2025-01-27
• Completion: 2025-01-27
• First posted: 2019-10-18
• Last updated: 2025-04-16

Locations

5 sites across 4 countries: France, Greece, Italy, Netherlands