Amyloidosis Clinical Trial
— AMYDARAOfficial title:
A Multicentre Open Label Phase II Study of Daratumumab in AL Amyloidosis Patients Not in VGPR or Better
Verified date | July 2021 |
Source | University Hospital, Limoges |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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
Status | Completed |
Enrollment | 40 |
Est. completion date | October 2020 |
Est. primary completion date | October 5, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Patients must be >18 years of age 2. Histologic diagnosis of AL amyloidosis 3. Genetic testing must be negative for transthyretin mutations 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 5. Patients should have received at least one line with an alkylating agent and/or a proteasome inhibitor and dexamethasone and not be in VGPR or CR at the time of inclusion 6. Measurable hematologic disease: 7. Symptomatic organ involvement 8. 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, 9. Adequate bone marrow function prior to 1st drug intake 10. Adequate organ function defined as: 11. Women with childbearing potential must be practicing one of the effective methods of birth control 12. 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 13. Only patients who are informed of the investigational nature of this study and sign and give written informed consent Exclusion Criteria: 1. 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 2. Isolated soft tissue involvement 3. Presence of non-AL amyloidosis 4. Bone marrow plasma cells >30% on bone marrow aspirate at screening 5. Cardiac mayo stage IIIb disease. 6. Repetitive ventricular arrhythmias on 24h Holter ECG despite anti-arrhythmic treatment, except if a pacemaker has been implanted. 7. Chronic atrial fibrillation 8. Supine systolic blood pressure <100 mmHg 9. 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 10. Clinically overt multiple myeloma with lytic bone lesions 11. Patients with uncontrolled infection or active malignancy 12. Any uncontrolled or severe cardiovascular or pulmonary disease 13. 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 14. Subjects with known chronic obstructive pulmonary disease (COPD) 15. Subject has known moderate or severe persistent asthma within the past 2 years 16. Previous anti-CD38 therapy 17. Hypersensitivity to Dexamethasone that would prohibit treatment with study therapy 18. Known positive for HIV or active hepatitis B or C 19. Refusal to consent or protected by legal regime |
Country | Name | City | State |
---|---|---|---|
France | CHU d'Angers | Angers | |
France | CHU de Caen | Caen | |
France | CHU de Limoges | Limoges | |
France | CHU de Lyon Sud | Lyon | |
France | APHP - Necker | Paris | |
France | APHP - Saint Antoine | Paris | |
France | APHP - Saint Louis | Paris | |
France | CHU Poitiers | Poitiers | |
France | CHU de Rennes | Rennes | |
Italy | Amyloidosis Research and Treatment Center | Pavia |
Lead Sponsor | Collaborator |
---|---|
University Hospital, Limoges |
France, Italy,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03. | Every month during 1 year |
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