Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02816476 |
Other study ID # |
I15015/AMYDARA |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
September 2016 |
Est. completion date |
October 2020 |
Study information
Verified date |
July 2021 |
Source |
University Hospital, Limoges |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This is a Phase II, single-arm, multicentre study of Daratumumab (16mg/kg IV route) in adult
patients with Light-Chain (AL) Amyloidosis who are not in VGPR or better after previous
treatment. A sample size of 40 patients who meet all eligibility criteria will be enrolled to
receive study treatment. Patients will receive treatment until either disease progression or
toxicity has occurred with a maximum planned of six 28-day cycles.
Daratumumab will be administrated every week for the first 2 cycles then. every 2 weeks from
cycle 3 through cycle 6.
Patients will also receive best supportive care (BSC) to mitigate Daratumumab side-effects,
and to address underlying Amyloidosis, including blood product transfusions, antimicrobials,
and (as appropriate) growth factors including granulocyte colony-stimulating factors for
neutropenia, erythropoietin for anaemia, and/or transfusions for thrombocytopenia
Description:
Systemic AL amyloidosis is a rare disease caused by the deposition of misfolded monoclonal
immunoglobulin free light chains (FLC) in various tissues and organs. It is usually
associated with a clonal plasma cell dyscrasia with a low tumour burden. Treatment of AL
amyloidosis relies mainly on chemotherapy aimed at suppressing the underlying plasma cell
clone secreting monoclonal FLC. The organ responses and the survival are greatly influenced
by the degree of hematological response evaluated by the decrease in serum FLC that has been
the principal endpoint in recent trials in AL amyloidosis. The goal of treatment is to reach
at least a very good partial response (VGPR) defined as a difference between the involved FLC
and the normal <40 mg/l.
Over the last 2 years, Daratumumab, a novel, high-affinity, therapeutic, human monoclonal
antibodies (mAb) that specifically recognizes the CD38 epitope has emerged as a breakthrough
targeted therapy for patients with myeloma. Taking into account that, in 90% of AL patients,
the monoclonal cells producing amyloidogenic FLC are Cluster of Differentiation 38 (CD38)
expressing plasma cells Daratumumab should be a promising treatment in AL amyloidosis.
The study will consist of 4 steps:
- A 21 day screening period This period start with screening visit which may occurs up to
21 days before the first study drug administration. After signature of the informed
consent form, procedures will be performed to ensure patient meet all
inclusion/exclusion criteria and document health status to receive study treatment.
These assessments will include quality of life questionnaires
- A treatment period Patient eligible to enter the study will receive 6 cycles of 28 days
of intra venous Daratumumab. During cycles 1 and 2, Daratumumab will be administered
weekly at days 1, 8, 15, and 22 then from cycles 3 to 6, Daratumumab will be
administered every two weeks at days 1 and 15. Patient will have assessments at the
ignition of a new cycle to document haematological and organs response and intra cycle
to watch for toxicities.
- An end of study visit (when PD or unacceptable adverse events occurs, or planned end of
study visit). Study procedures will be performed at 28 days (± 15) after the last dose
of study medication for all patients, including early termination patients.
- Followup period After treatment discontinuation, followup will be made to the patient
every 3 months for at least 1 year to inquire about the patient's hematological and
organ status, general health, and information on any new medical events.
DOSING REGIMEN
Daratumumab. Six 28-day cycles, 16 mg/kg administered by IV route, During cycle 1 and 2,
Daratumumab will be administered weekly at days 1, 8, 15, and 22
For cycles 3 to 6, Daratumumab will be administered every other week at days 1 and 15