AL amyloidosis MedDRA version: 20.0 Level: PT Classification code 10002022 Term: Amyloidosis System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: Imnovid
Product Name: Pomalidomide
Product Code: [Pomalidomide]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: pomalidomide
CAS Number: 19171-19-8
Current Sponsor code: ---
Concen
Sponsors
FONDAZIONE I.R.C.C.S. POLICLINICO SAN MATTEO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologic diagnosis of AL amyloidosis; 2. Patients should have received at least one line (and no more than 3 lines) with an alkylating agentand/or a PIn and dexamethasone and not be in VGPR or CR at the time of inclusion (patients who did not reach VGPR or patients in VGPR or better but with an hematological relapse can be included); 3. Measurable hematologic disease: difference between involved and uninvolved FLC > 20 mg/L with an abnormal ¿/¿ ratio; 4. Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system) (See attachment 1); 5. 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. Treatment from previous therapy should be in accordance to the local clinical practice in which a 4 weeks period is required for the evaluation of response; 6. Adequate bone marrow function prior to 1st drug intake (C1D1), without transfusion or growth factor support within 5 days prior to 1st drug intake, defined as: - Absolute neutrophils = 1000/mm3, - Platelets = 50000/mm3, - Hemoglobin = 9.0 g/dL, 7. Adequate organ function defined as: - Serum SGOT/AST or SGPT/ALT =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 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 (cardiac stage IIIb patients); 5. Repetitive ventricular arrhythmias on 24h Holter ECG despite anti-arrhythmic treatment, except if a pacemaker has been implanted; 6. Chronic atrial fibrillation with uncontrolled heart rate; 7. Supine systolic blood pressure <100 mmHg; 8. Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant; 9. Subjects with known chronic obstructive pulmonary disease or persistent asthma ; 10. Previous anti-CD38 or pomalidomide therapy; 11. Presence of other active malignancy with the exception of non-melanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate specific antigen is within normal limit, or any completely resected carcinoma in situ; 12. Subjects with known/underlying medical conditions that, in the investigator’s opinion would make the administration of the study drug hazardous (ie: uncontrolled diabetes or uncontrolled coronary artery disease); 13. Subject is: o (Known to be) seropositive for human immunodeficiency virus (HIV) o seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. o (Known to be) seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the rate good quality (i.e. CR+VGPR) hematologic response at the completion of 6 cycles of Daratumumab plus pomalidomide in patients with R/R AL amyloidosis not in VGPR or better after any previous therapy.;Secondary Objective: To determine safety and tolerability of Daratumumab plus pomalidomide (type, frequency, severity, drug discontinuation for toxicity or intolerance, dose modification/delay and relationship of adverse events to study treatment). To assess in all patients • Overall Hematologic Response Rate • The Overall Hematologic Response Rate including PR at the completion of 6 cycles; • The duration of hematologic response; • The rate of organ response and organ improvement, according to standard criteria; • The time to hematologic and organ response; • The hematologic disease progression free survival (PFS) and 1-year PFS; • The overall survival (OS) and 1-year OS; • MRD negativity rate according to next generation flow cytometry. To assess quality of life (QoL) using EQ5D-5L.;Primary end point(s): VGPR;Timepoint(s) of evaluation of this end point: 6 months | — |
Countries
Italy
Contacts
Public ContactUOC Laboratorio Biochimica - Biotec
Fondazione IRCCS Policlinico San Matteo
Outcome results
None listed