Daratumumab Therapy for Patients With Refractory or Relapsed AL Amyloidosis

NCT02816476 | Completed Phase 2 DMC

• 1 other identifier: I15015/AMYDARA
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 10

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

Conditions

Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  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.

  After 6 cycles treatment (6 months).

Secondary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03.

  Every month during 1 year

Study Arms (1)

Daratumumab

EXPERIMENTAL

Patient will receive Daratumumab every week for the first 2 cycles then every 2 weeks from cycle 3 through cycle 6.

Drug: Daratumumab

Interventions

Daratumumab DRUG

Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be \>18 years of age
• Histologic diagnosis of AL amyloidosis
• Genetic testing must be negative for transthyretin mutations
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Measurable hematologic disease:
• Symptomatic organ involvement
• Wash-out period of at least 4 weeks from previous antitumor therapy or any investigational treatment or 5 half-lives from previous antibodies, whichever is longer,
• Adequate bone marrow function prior to 1st drug intake
• Adequate organ function defined as:
• Women with childbearing potential must be practicing one of the effective methods of birth control
• A man who has not had a vasectomy and who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control
• Only patients who are informed of the investigational nature of this study and sign and give written informed consent

You may not qualify if:

• Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura as the only evidence of disease. The finding of isolated vascular amyloid in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis
• Isolated soft tissue involvement
• Presence of non-AL amyloidosis
• Bone marrow plasma cells \>30% on bone marrow aspirate at screening
• Cardiac mayo stage IIIb disease.
• Repetitive ventricular arrhythmias on 24h Holter ECG despite anti-arrhythmic treatment, except if a pacemaker has been implanted.
• Chronic atrial fibrillation
• Supine systolic blood pressure \<100 mmHg
• Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of any component of the treatment regimen. Or, subject is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of any component of the treatment regimen
• Clinically overt multiple myeloma with lytic bone lesions
• Patients with uncontrolled infection or active malignancy
• Any uncontrolled or severe cardiovascular or pulmonary disease
• Subjects with psychiatric illnesses or social situations that would preclude them understanding the informed consent, study compliance or the ability to tolerate study procedures and/or study therapy
• Subjects with known chronic obstructive pulmonary disease (COPD)
• Subject has known moderate or severe persistent asthma within the past 2 years

Sponsors & Collaborators

• University Hospital, Limoges: lead

Study Sites (10)

CHU d'Angers

Angers, France

Location

CHU de Caen

Caen, 14000, France

Location

CHU de Limoges

Limoges, 87042, France

Location

CHU de Lyon Sud

Lyon, France

Location

APHP - Necker

Paris, France

Location

APHP - Saint Antoine

Paris, France

Location

APHP - Saint Louis

Paris, France

Location

CHU Poitiers

Poitiers, France

Location

CHU de Rennes

Rennes, France

Location

Amyloidosis Research and Treatment Center

Pavia, Italy

Location

MeSH Terms

Conditions

Amyloidosis

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2016
• First Posted: June 28, 2016
• Study Start: September 1, 2016
• Primary Completion: October 5, 2019
• Study Completion: October 1, 2020
• Last Updated: July 9, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); FR (9)