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.
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
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.
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 group | Role | What they receive |
|---|---|---|
| Daratumumab | Experimental | Daratumumab, 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.
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)
Time to Next Treatment
Number of months from study drug initiation to starting another treatment
Measured: Up to 3 years
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
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.
- First posted21 Jul 2016 (estimated)
- Study start20 Mar 2017
- Primary completion28 May 2020
- Study completion17 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AL AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Boston Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Vaishali Sanchorawala, MD, Principal investigator, Boston Medical Center
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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