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AL AmyloidosisPhase 2DarPALNCT04895917

Daratumumab and Pomalidomide in Previously Treated Patients With AL Amyloidosis

A Phase 2 study testing daratumumab and pomalidomide in people with AL Amyloidosis, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 3 sites in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 99 years
Conditions the study is for
AL Amyloidosis
What is being tested?
daratumumab and pomalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
3 sitesItaly
Study dates
23 Jun 2021to 15 Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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, 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);
  • 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.

Who cannot join

  • 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;
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  • 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).

Trial locations and contacts

3 sites in 1 country.

Italy3 sites

  • Policlinico Universitario "Mater Domini"

    Catanzaro

  • Foundation IRCCS Policlinico San Matteo

    Pavia, 27100

  • Università Campus Biomedico

    Rome

Other trials in Italy

About this study

Official title: A Multi-center Open Label Phase II Study of Daratumumab and Pomalidomide in Previously Treated Patients With AL Amyloidosis.

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

Read the detailed 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.

Conditions
AL Amyloidosis
Being tested
daratumumab and pomalidomide
Keywords
AL Amyloidosis, Daratumumab, Pomalidomide, relapsed/refractory AL Amyloidosis
Medical subject headings
Immunoglobulin Light-chain Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • daratumumab and pomalidomideDrug

    Patient eligible to enter the study will receive 6 cycles of 28 days of subcutaneous Daratumumab (1800 mg SC) and oral pomalidomide 4 mg from day 1 to day 21. During cycle 1 and 2, Daratumumab will be administered weekly at days 1, 8, 15, and 22 then from cycle 3 to 6, Daratumumab will be administered every other week at days 1 and 15.

Study groups in NCT04895917
Study groupRoleWhat they receive
Pomalidomide and daratumumabExperimentalNot described
Receives: Drug: daratumumab and pomalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of good quality (i.e. CR+VGPR) hematologic response.

    To assess the rate of good quality (i.e. CR+VGPR) hematologic response at the completion of 6 cycles of Daratumumab plus pomalidomide in patients with relapsed/refractory AL amyloidosis not in VGPR or better after any previous therapy.

    Measured: 6 months

Secondary outcomes (9)

  1. To assess in all patients according to their disease history the overall Hematologic Response Rate (CR, VGPR, LowdFLC partial response and PR) at the completion of 1st and 3rd cycles.

    Measured: At the end of Cycle 1 and Cycle 3 (each cycle is 28 days)

  2. To assess in all patients the overall Hematologic Response Rate including PR at the completion of 6 cycles.

    Measured: 6 months

  3. To assess in all patients duration of hematologic response. After treatment discontinuation, follow-up will be made to the patient every 3 months for at least 1 year.

    Measured: 1 year after treatment discontinuation

  4. To assess in all patients the rate of organ response (i.e. cardiac response: NT-proBNB measurement; renal response: proteinuria measurement) and organ improvement, according to standard criteria (Palladini et al JCO 2012, Palladini et al Blood 2014).

    Measured: 6 months

  5. To assess in all patients the time from the screening to hematologic and organ response.

    Measured: 6 months

  6. To assess in all patients the hematologic disease progression free survival (PFS) from screening and 1-year PFS from screening (months).

    Measured: 1 year

  7. To assess in all patients the overall survival (OS) from screening and 1-year OS from screening (months).

    Measured: 1 year

  8. To assess in all patients the MRD negativity rate according to next generation flow cytometry.

    Measured: 6 months

  9. To assess quality of life (QoL) using EQ5D-5L.

    Measured: 1 year after treatment discontinuation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2021
  2. Study start23 Jun 2021
  3. Primary completion18 Dec 2024
  4. Study completion15 Jan 2025

Why it stopped: low patient enrollment rate

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04895917
Sponsor's protocol ID
AC-016-IT
Acronym
DarPAL
Status last verified
Feb 2025
First submitted
10 May 2021
Last updated
20 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing daratumumab and pomalidomide in people with AL Amyloidosis, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 3 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: low patient enrollment rate). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of good quality (i.e. CR+VGPR) hematologic response. (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04895917.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2025.

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