Daratumumab Therapy for Patients With Refractory or Relapsed AL Amyloidosis

• Status: Completed
• Trial end date: 2020-10-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Limoges
• Treatments: Antibodies, Monoclonal; Daratumumab

Criteria

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