IsAMYP: This phase II study is trying to understand how effective a combined treatment of targeted therapy (isatuximab and pomalidomide) and steroids (dexamethasone) (IPd) is in people with AL amyloidosisA Phase 2, Open Label, Multicenter, Single-stage Study to Evaluate the Efficacy of Isatuximab Plus Pomalidomide and Dexamethasone (IPd), in Patients With AL Amyloidosis Not in VGPR or Better After Any Previous Therapy

Exclusion

1. Presence of non-AL amyloidosis
2. AL amyloidosis with isolated soft tissue involvement
3. Bone marrow plasma cells >30% and clinically symptomatic multiple myeloma with lytic bone lesions
4. NT-proBNP > 8500 ng/L and hs-troponin I > 100 ng/L or hs-troponin T > 50 ng/L (cardiac stage IIIb patients)
5. Repetitive ventricular arrhythmias on 24h Holter ECG despite anti-arrhythmic treatment sustained ventricular tachycardia, aborted ventricular fibrillation, atrioventricular nodal or sinoatrial nodal dysfunction with no pacemaker
6. Chronic atrial fibrillation with uncontrolled heart rate
7. Significant cardiac dysfunction; myocardial infarction within 12 months; unstable poorly controlled angina pectoris
8. Uncorrected valvular disease unrelated to AL amyloid cardiomyopathy
9. QT interval as corrected by Fridericia's formula >550 msec without pacemaker,
10. Undergoing dialysis
11. Ongoing toxicity (excluding alopecia and those listed in eligibility criteria) from any prior therapy >G1 (NCI-CTCAE v5.0)
12. Supine systolic blood pressure <90 mm Hg, or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of <80 mmHg despite medical management (i.e. midodrine, fludrocortisones) in the absence of volume depletion
13. Previous anti-CD38 therapy or Pomalidomide therapy (if refractory to Pomalidomide)
14. Hypersensitivity to IMiD® defined as any hypersensitivity reaction leading to stop IMiD® within the 2 first cycles or toxicity, which does meet intolerance definition
15. Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, polysorbate 80, poloxamer 188, sucrose or any of the other components of study treatment that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents
16. History of malignancy (other than AL amyloidosis) within 3 years before the date of inclusion (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
17. Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results
18. Active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics
19. Received any investigational drug within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer. In case of very aggressive disease (i.e acute leukemia) delay could be shortened after agreement between sponsor and investigator, in absence of residual toxicities from previous therapy

20. Known positive for HIV or active hepatitis A, B or C:

    • Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA

    Of note:

    Patient can be eligible if anti-HBc IgG positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative.

    • If anti-HBV therapy in relation with prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period.

    Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met.

    • Active HCV infection: positive HCV RNA and negative anti-HCV.

    Of note:

    Patients with antiviral therapy for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion.

    Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible

21. Pregnant or breast-feeding females