Overview

Daratumumab and Pomalidomide in Previously Treated Patients With AL Amyloidosis

Status:
Recruiting
Trial end date:
2024-03-31
Target enrollment:
0
Participant gender:
All
Summary
This study aims at establishing a new powerful combination of daratumumab and pomalidomide as rescue treatment for patients with R/R AL amyloidosis.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
IRCCS Policlinico S. Matteo
Treatments:
Daratumumab
Pomalidomide
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 agent and/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 k/l ratio;

4. Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous
system);

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 < 3.0 X Upper Limit of the normal range (ULN),

- Serum total bilirubin level<1.5x ULN, unless for subjects with Gilbert's syndrome
where the direct bilirubin should then be ≤2.0 x ULN.

8. Female patients who are postmenopausal for at least 1 year before the screening visit,
or are surgically sterile, or if they are of childbearing potential, agree to practice
effective methods of contraception from the time of signing the informed consent
through 30 days after the last dose of study drug, or agree to completely abstain from
intercourse (serum pregnancy test has to be performed for all women of childbearing
potential at the beginning of each cycle during the study. In addition, a pregnancy
test may be done at any time during the study at the discretion of the investigator if
a subject miss a period or has unusual menstrual bleeding);

9. Voluntary written consent must be given before performance of any study-related
procedure not part of standard medical care with the understanding that consent may be
withdrawn by the patient at any time without prejudice to future medical care.

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
oruncontrolled coronary artery disease);

13. Subject is:

- (Known to be) seropositive for human immunodeficiency virus (HIV)

- 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.

- (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).