Clinical Trial: Daratumumab Therapy for Patients With Refractory or Relapsed AL Amyloidosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Multicentre Open Label Phase II Study of Daratumumab in AL Amyloidosis Patients Not in VGPR or Better

Brief 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

Detailed Summary:

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 Dar
  Sponsor: University Hospital, Limoges
  

  Current Primary Outcome: Overall Response Rate [ Time Frame: After 6 cycles treatment (6 months). ]

  Overall Response Rate (CR+VGPR) at the completion of 6 cycles of Daratumumab using the new response criteria (J Clin Oncol, 2012. 30(36): p. 4541-9.
  
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome: Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03. [ Time Frame: Every month during 1 year ]
  
  

  Original Secondary Outcome: Same as current
  
  Information By: University Hospital, Limoges
  

  Dates:
  Date Received: June 22, 2016
  Date Started: September 2016
  Date Completion: June 2019
  Last Updated: September 13, 2016
  Last Verified: June 2016