Daratumumab and Pomalidomide in Previously Treated Patients With AL Amyloidosis (DarPAL)

  • STATUS
    Recruiting
  • End date
    Mar 31, 2024
  • participants needed
    40
  • sponsor
    IRCCS Policlinico S. Matteo
Updated on 8 August 2022
bone marrow procedure
dexamethasone
daratumumab
alkylating agent

Summary

This study aims at establishing a new powerful combination of daratumumab and pomalidomide as rescue treatment for patients with R/R AL amyloidosis.

Description

Despite recent advance in understanding the biology of the amyloidogenic clone and despite the availability of different therapeutic options, there are still patients who fail to respond to fist line therapy and experience relapse after response to first line regimens. The toxicity profile of daratumumab resulted favorable in the setting of advanced AL amyloidosis patients with severe organ damage. Pomalidomide has proven to be effective as a single agent in R/R AL amyloidosis with a better safety profile over lenalidomide because of relevant renal toxicity of the latter drug in presence of nephrotic proteinuria. Daratumumab is a recently released mAb that has shown deep hematological responses in R/R multiple myeloma with a favorable toxicity. Up-to-date clinical data have further demonstrated the high efficacy of combination regimens including an ImiD/Daratumumab combination in R/R multiple myeloma reaching unprecedented results in terms of response rate, progression free survival (PFS) and minimal residual disease (MRD) negativity.

On these bases, the present study aims to explore the doublet Daratumumab/pomalidomide in R/R AL amyloidosis. The goal of the study is to obtain rapid, durable and deep hematological responses with a low toxicity profile. The expectation is to attain a very favorable benefit/risk ratio from this combination as these patients should experience a low rate of treatment discontinuation, hospitalization due AEs and/or disease progression and/or organ failures.

Details
Condition AL Amyloidosis
Treatment daratumumab and pomalidomide
Clinical Study IdentifierNCT04895917
SponsorIRCCS Policlinico S. Matteo
Last Modified on8 August 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologic diagnosis of AL amyloidosis
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)
Measurable hematologic disease: difference between involved and uninvolved FLC > 20 mg/L with an abnormal k/l ratio
Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system)
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
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
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
Female patients who are postmenopausal for at least 1 year before the screening visit
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
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)

Exclusion Criteria

Presence of non-AL amyloidosis
AL amyloidosis with isolated soft tissue involvement
Bone marrow plasma cells >30% and clinically symptomatic multiple myeloma with lytic bone lesions
NT-proBNP >8500 ng/L and hs-troponin I >100 ng/L (cardiac stage IIIb patients)
Repetitive ventricular arrhythmias on 24h Holter ECG despite anti-arrhythmic treatment, except if a pacemaker has been implanted
Chronic atrial fibrillation with uncontrolled heart rate
Supine systolic blood pressure <100 mmHg
Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant
Subjects with known chronic obstructive pulmonary disease or persistent asthma
Previous anti-CD38 or pomalidomide therapy
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
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)
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)
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