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AL AmyloidosisPhase 1/2NCT02841033

Daratumumab for the Treatment of Patients With AL Amyloidosis

A Phase 1/2 study testing daratumumab in people with AL Amyloidosis, run by Boston Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Participants with AL Amyloidosis will receive the drug daratumumab by IV infusion once weekly for two months, then every 2 weeks for four months, then once each month. Study treatment may continue until disease progression, unacceptable toxicity, or decision to withdraw from the trial. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
AL Amyloidosis
What is being tested?
daratumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
20 Mar 2017to 17 Jul 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological diagnosis of primary systemic (AL) amyloidosis:
  • At least one tissue demonstrating positive Congo Red staining with characteristic apple green birefringence AND
  • Evidence of a clonal plasma cell dyscrasia:
  • Monoclonal protein in the serum and/or urine by immunofixation electrophoresis AND/OR ii. Abnormal serum free light chain assay AND/OR iii. Clonal plasma cell population in the bone marrow demonstrated by immunohistochemistry, flow cytometry or in situ hybridization AND
  • Evidence of organ involvement other than carpal tunnel syndrome. Confirmation of tissue diagnosis at all sites of organ dysfunction is encouraged, but not required.
  • Must have relapsed after or been refractory to at least one prior treatment regimen of proven efficacy in the treatment of AL amyloidosis
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  • Must be > 18 years of age.
  • Must have a performance status of 0-2 by Eastern Cooperative Oncology Group (ECOG) criteria
  • Must have adequate hepatic function as evidenced by serum bilirubin values < 2.0 mg/dL; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) < 3x upper limit of normal (ULN).
  • Must have an absolute neutrophil count ≥1000/mm3, hemoglobin ≥7.5 g/dL, and platelet count ≥50×109/L

Who cannot join

  • • Renal Insufficiency (CrCL <20mL/min), calculated by Cockcroft-Gault Equation Creatinine Clearance = Sex * ((140 - Age) / (SerumCreat)) * (Weight / 72) Equation parameters such as sex have two or more discrete values that may be used in the calculation. The numbers in the parentheses, e.g. (1), represent the values that will be used. The default unit of measure for weight is kilograms. Please verify that the correct unit of measure has been selected.
  • Mayo clinic cardiac biomarker stage IIIb
  • Evidence of significant cardiovascular conditions as specified below:
  • B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide (NT-ProBNP) > 8500 ng/L (Mayo Stage IIIb patients are excluded)
  • New York Heart Association (NYHA) classification IIIB or IV heart failure
  • Unstable Angina, Arrhythmia, prolonged corrected QT (QTc) interval, symptomatic orthostatic hypotension, or supine systolic blood pressure < 90 mm Hg.
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  • left ventricular ejection fraction (LVEF) <40%
  • Overt multiple myeloma (>30% bone marrow plasmacytosis, extensive (>2) lytic lesions, or hypercalcemia).
  • Plan for autologous stem cell transplant in the six months prior to study drug (stem cell collection is permitted during the first six months of study treatment)
  • Any form of secondary or familial (ATTR) amyloidosis
  • The presence or history of another malignancy is not allowed except for the following:
  • adequately treated basal cell or squamous cell skin cancer,
  • in situ cervical cancer,
  • adequately treated Stage I or II cancer from which the patient is currently in complete remission, any other cancer from which the patient has been disease-free for 5 years.
  • Known to be Human Immunodeficiency Virus (HIV) positivity.
  • Pregnant or nursing women. Women and men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
  • Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume at one second (FEV1) <50% of predicted normal. Note that forced expiratory volume at one second FEV1 testing is required for patients suspected of having COPD.
  • Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Boston Medical Center

    Boston, Massachusetts, 02118

Other trials in United States

About this study

Official title: A Phase I-II Trial of Daratumumab for the Treatment of Patients With AL Amyloidosis

Participants with AL Amyloidosis will receive the drug daratumumab by IV infusion once weekly for two months, then every 2 weeks for four months, then once each month. Study treatment may continue until disease progression, unacceptable toxicity, or decision to withdraw from the trial. Disease evaluations will be performed every three months until disease progression.

Read the detailed description

This Phase I/II study is intended to evaluate the safety and tolerability of infusion of daratumumab in AL amyloidosis, specifically with respect to infusion reactions. In addition, the investigators would like to assess organ response with respect to cardiac biomarkers and proteinuria, as well as hematologic response and time to next treatment. Participants with AL Amyloidosis will receive the drug daratumumab by IV infusion once weekly for two months, then every 2 weeks for four months, then once each month. Study treatment may continue until disease progression, unacceptable toxicity, or decision to withdraw from the trial. Disease evaluations will be performed every three months until disease progression.

Conditions
AL Amyloidosis
Being tested
daratumumab
Keywords
Daratumumab
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.

  • daratumumabDrug

    Also called Darzalex

    Daratumumab by IV infusion once weekly for two months, then every 2 weeks for four months, then once each month until progression or inability to tolerate.

Study groups in NCT02841033
Study groupRoleWhat they receive
DaratumumabExperimentalDaratumumab, 16mg/kg body weight in 1000 mL for the first dose, followed by 500mL for subsequent doses, once weekly for two months, then every 2 weeks for four months, then once each month.
Receives: Drug: daratumumab

What is being measured

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

  1. Assess the Number of Patients Who Respond to Treatment

    Number of participants with response and ability to tolerate study treatment in each of these categories: Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD).

    All participants were able to tolerate study treatment.

    Per protocol, overall response designations are a combination of hematologic response.

    A CR is defined as negative serum and urine immunofixation electrophoresis with normal serum free light chain ratio; a VGPR is reduction in the dFLC* to <40 mg/L, a PR is dFLC reduction by >50%; SD is not meeting criteria for CR, VGPR, PR, or PD; and PD is an increase in FLC of 50% to >100 mg/L.

    • "dFLC" is difference in involved and uninvolved serum Free Light-Chain levels.

    Measured: 3 months

Secondary outcomes (3)

  1. Time to Next Treatment

    Number of months from study drug initiation to starting another treatment

    Measured: Up to 3 years

  2. Assess Hematologic Response Based on Blood and Urine Testing Using Standard Criteria

    Number of patients with hematologic complete response (CR), very good partial response (VGPR), or partial response (PR).

    Per protocol, a hematologic CR is defined as negative serum and urine immunofixation electrophoresis with normal serum free light chain ratio; a VGPR is reduction in the dFLC* to <40 mg/L; and a PR is dFLC reduction by >50%.

    • "dFLC" is difference in involved and uninvolved serum free light-chain levels

    Measured: 3 months

  3. Assess Organ Responses Based on Standard Criteria Included in Protocol

    Number of patients with organ response based on standard criteria included in protocol.

    Cardiac response is defined as: NT-proBNP response (>30% and >300 ng/L decrease in patients with a baseline NT-proBNP >650 ng/L; and/or NYHA class response (> two-class decrease if baseline NYHA class 3 or 4)

    Renal response is defined as: Decrease in proteinuria by > 30% or below 0.5 g/24 h without renal progression. Serum creatinine and creatinine clearance must not worsen by 25% over baseline

    Measured: 3 months

Timeline

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

  1. First posted21 Jul 2016 (estimated)
  2. Study start20 Mar 2017
  3. Primary completion28 May 2020
  4. Study completion17 Jul 2020

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02841033
Sponsor's protocol ID
H-35360
Other IDs
54767414AMY2002
Status last verified
Apr 2021
First submitted
14 Jun 2016
Last updated
7 May 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Sanchorawala V, Sarosiek S, Schulman A, Mistark M, Migre ME, Cruz R, Sloan JM, Brauneis D, Shelton AC. Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study. Blood. 2020 Apr 30;135(18):1541-1547. doi: 10.1182/blood.2019004436.

    PubMed 31978210

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing daratumumab in people with AL Amyloidosis, run by Boston Medical Center at 1 site in United States.

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 10 inclusion and 18 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: finished, as of the sponsor's last update on 7 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Yes. Results are posted in the registry (first posted 7 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Assess the Number of Patients Who Respond to Treatment (time frame: 3 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 NCT02841033, which also lists 1 linked publication.

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 7 May 2021.

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