AmyloidosisPhase 2AMYDARANCT02816476
Daratumumab Therapy for Patients With Refractory or Relapsed AL Amyloidosis
A Phase 2 study testing Daratumumab in people with Amyloidosis, run by University Hospital, Limoges at 10 sites in 2 countries.
Trial summary
This is a Phase II, single-arm, multicentre study of Daratumumab (16mg/kg IV route) in adult patients with Light-Chain (AL) Amyloidosis who are not in VGPR or better after previous treatment. A sample size of 40 patients who meet all eligibility criteria will be enrolled to receive study treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyloidosis
- What is being tested?
- Daratumumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Sep 2016to Oct 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be >18 years of age
- Histologic diagnosis of AL amyloidosis
- Genetic testing must be negative for transthyretin mutations
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Patients should have received at least one line with an alkylating agent and/or a proteasome inhibitor and dexamethasone and not be in VGPR or CR at the time of inclusion
- Measurable hematologic disease:
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- Symptomatic organ involvement
- 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,
- Adequate bone marrow function prior to 1st drug intake
- Adequate organ function defined as:
- Women with childbearing potential must be practicing one of the effective methods of birth control
- A man who has not had a vasectomy and who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control
- Only patients who are informed of the investigational nature of this study and sign and give written informed consent
Who cannot join
- Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura as the only evidence of disease. The finding of isolated vascular amyloid in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis
- Isolated soft tissue involvement
- Presence of non-AL amyloidosis
- Bone marrow plasma cells >30% on bone marrow aspirate at screening
- Cardiac mayo stage IIIb disease.
- Repetitive ventricular arrhythmias on 24h Holter ECG despite anti-arrhythmic treatment, except if a pacemaker has been implanted.
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- Chronic atrial fibrillation
- Supine systolic blood pressure <100 mmHg
- Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of any component of the treatment regimen. Or, subject is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of any component of the treatment regimen
- Clinically overt multiple myeloma with lytic bone lesions
- Patients with uncontrolled infection or active malignancy
- Any uncontrolled or severe cardiovascular or pulmonary disease
- Subjects with psychiatric illnesses or social situations that would preclude them understanding the informed consent, study compliance or the ability to tolerate study procedures and/or study therapy
- Subjects with known chronic obstructive pulmonary disease (COPD)
- Subject has known moderate or severe persistent asthma within the past 2 years
- Previous anti-CD38 therapy
- Hypersensitivity to Dexamethasone that would prohibit treatment with study therapy
- Known positive for HIV or active hepatitis B or C
- Refusal to consent or protected by legal regime
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
France9 sites
CHU d'Angers
Angers
CHU de Caen
Caen, 14000
CHU de Limoges
Limoges, 87042
CHU de Lyon Sud
Lyon
APHP - Necker
Paris
APHP - Saint Antoine
Paris
APHP - Saint Louis
Paris
CHU Poitiers
Poitiers
CHU de Rennes
Rennes
About this study
Official title: A Multicentre Open Label Phase II Study of Daratumumab in AL Amyloidosis Patients Not in VGPR or Better
This is a Phase II, single-arm, multicentre study of Daratumumab (16mg/kg IV route) in adult patients with Light-Chain (AL) Amyloidosis who are not in VGPR or better after previous treatment. A sample size of 40 patients who meet all eligibility criteria will be enrolled to receive study treatment. Patients will receive treatment until either disease progression or toxicity has occurred with a maximum planned of six 28-day cycles.
Daratumumab will be administrated every week for the first 2 cycles then. every 2 weeks from cycle 3 through cycle 6.
Patients will also receive best supportive care (BSC) to mitigate Daratumumab side-effects, and to address underlying Amyloidosis, including blood product transfusions, antimicrobials, and (as appropriate) growth factors including granulocyte colony-stimulating factors for neutropenia, erythropoietin for anaemia, and/or transfusions for thrombocytopenia
Read the detailed description
Systemic AL amyloidosis is a rare disease caused by the deposition of misfolded monoclonal immunoglobulin free light chains (FLC) in various tissues and organs. It is usually associated with a clonal plasma cell dyscrasia with a low tumour burden. Treatment of AL amyloidosis relies mainly on chemotherapy aimed at suppressing the underlying plasma cell clone secreting monoclonal FLC. The organ responses and the survival are greatly influenced by the degree of hematological response evaluated by the decrease in serum FLC that has been the principal endpoint in recent trials in AL amyloidosis. The goal of treatment is to reach at least a very good partial response (VGPR) defined as a difference between the involved FLC and the normal <40 mg/l.
Over the last 2 years, Daratumumab, a novel, high-affinity, therapeutic, human monoclonal antibodies (mAb) that specifically recognizes the CD38 epitope has emerged as a breakthrough targeted therapy for patients with myeloma. Taking into account that, in 90% of AL patients, the monoclonal cells producing amyloidogenic FLC are Cluster of Differentiation 38 (CD38) expressing plasma cells Daratumumab should be a promising treatment in AL amyloidosis.
The study will consist of 4 steps:
- A 21 day screening period This period start with screening visit which may occurs up to 21 days before the first study drug administration. After signature of the informed consent form, procedures will be performed to ensure patient meet all inclusion/exclusion criteria and document health status to receive study treatment. These assessments will include quality of life questionnaires
- A treatment period Patient eligible to enter the study will receive 6 cycles of 28 days of intra venous Daratumumab. During cycles 1 and 2, Daratumumab will be administered weekly at days 1, 8, 15, and 22 then from cycles 3 to 6, Daratumumab will be administered every two weeks at days 1 and 15. Patient will have assessments at the ignition of a new cycle to document haematological and organs response and intra cycle to watch for toxicities.
- An end of study visit (when PD or unacceptable adverse events occurs, or planned end of study visit). Study procedures will be performed at 28 days (± 15) after the last dose of study medication for all patients, including early termination patients.
- Followup period After treatment discontinuation, followup will be made to the patient every 3 months for at least 1 year to inquire about the patient's hematological and organ status, general health, and information on any new medical events.
DOSING REGIMEN
Daratumumab. Six 28-day cycles, 16 mg/kg administered by IV route, During cycle 1 and 2, Daratumumab will be administered weekly at days 1, 8, 15, and 22
For cycles 3 to 6, Daratumumab will be administered every other week at days 1 and 15
- Conditions
- Amyloidosis
- Being tested
- Daratumumab
- Medical subject headings
- Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaratumumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Daratumumab | Experimental | Patient will receive Daratumumab every week for the first 2 cycles then every 2 weeks from cycle 3 through cycle 6. Receives: Drug: Daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Overall Response Rate (CR+VGPR) at the completion of 6 cycles of Daratumumab using the new response criteria (J Clin Oncol, 2012. 30(36): p. 4541-9.
Measured: After 6 cycles treatment (6 months).
Secondary outcomes (1)
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03.
Measured: Every month during 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2016 (estimated)
- Study startSep 2016
- Primary completion5 Oct 2019
- Study completionOct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AmyloidosisStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02816476
- Sponsor's protocol ID
- I15015/AMYDARA
- Acronym
- AMYDARA
- Status last verified
- Jul 2021
- First submitted
- 22 Jun 2016
- Last updated
- 9 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Open Label Phase II Study of Daratumumab in AL Amyloidosis Patients Not in VGPR or Better
- ClinicalTrials.gov ID
- NCT02816476
- Acronym / sponsor ID
- AMYDARA / I15015/AMYDARA
- Conditions
- Amyloidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- 5 Oct 2019 (actual)
- Study completion
- Oct 2020 (actual)
- First posted
- 28 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II, single-arm, multicentre study of Daratumumab (16mg/kg IV route) in adult patients with Light-Chain (AL) Amyloidosis who are not in VGPR or better after previous treatment. A sample size of 40 patients who meet all eligibility criteria will be enrolled to receive study treatment. Patients will receive treatment until either disease progression or toxicity has occurred with a maximum planned of six 28-day cycles.
Daratumumab will be administrated every week for the first 2 cycles then. every 2 weeks from cycle 3 through cycle 6.
Patients will also receive best supportive care (BSC) to mitigate Daratumumab side-effects, and to address underlying Amyloidosis, including blood product transfusions, antimicrobials, and (as appropriate) growth factors including granulocyte colony-stimulating factors for neutropenia, erythropoietin for anaemia, and/or transfusions for thrombocytopenia
Detailed description
Systemic AL amyloidosis is a rare disease caused by the deposition of misfolded monoclonal immunoglobulin free light chains (FLC) in various tissues and organs. It is usually associated with a clonal plasma cell dyscrasia with a low tumour burden. Treatment of AL amyloidosis relies mainly on chemotherapy aimed at suppressing the underlying plasma cell clone secreting monoclonal FLC. The organ responses and the survival are greatly influenced by the degree of hematological response evaluated by the decrease in serum FLC that has been the principal endpoint in recent trials in AL amyloidosis. The goal of treatment is to reach at least a very good partial response (VGPR) defined as a difference between the involved FLC and the normal <40 mg/l.
Over the last 2 years, Daratumumab, a novel, high-affinity, therapeutic, human monoclonal antibodies (mAb) that specifically recognizes the CD38 epitope has emerged as a breakthrough targeted therapy for patients with myeloma. Taking into account that, in 90% of AL patients, the monoclonal cells producing amyloidogenic FLC are Cluster of Differentiation 38 (CD38) expressing plasma cells Daratumumab should be a promising treatment in AL amyloidosis.
The study will consist of 4 steps:
- A 21 day screening period This period start with screening visit which may occurs up to 21 days before the first study drug administration. After signature of the informed consent form, procedures will be performed to ensure patient meet all inclusion/exclusion criteria and document health status to receive study treatment. These assessments will include quality of life questionnaires
- A treatment period Patient eligible to enter the study will receive 6 cycles of 28 days of intra venous Daratumumab. During cycles 1 and 2, Daratumumab will be administered weekly at days 1, 8, 15, and 22 then from cycles 3 to 6, Daratumumab will be administered every two weeks at days 1 and 15. Patient will have assessments at the ignition of a new cycle to document haematological and organs response and intra cycle to watch for toxicities.
- An end of study visit (when PD or unacceptable adverse events occurs, or planned end of study visit). Study procedures will be performed at 28 days (± 15) after the last dose of study medication for all patients, including early termination patients.
- Followup period After treatment discontinuation, followup will be made to the patient every 3 months for at least 1 year to inquire about the patient's hematological and organ status, general health, and information on any new medical events.
DOSING REGIMEN
Daratumumab. Six 28-day cycles, 16 mg/kg administered by IV route, During cycle 1 and 2, Daratumumab will be administered weekly at days 1, 8, 15, and 22
For cycles 3 to 6, Daratumumab will be administered every other week at days 1 and 15
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Daratumumab | Experimental | Drug: DaratumumabPatient will receive Daratumumab every week for the first 2 cycles then every 2 weeks from cycle 3 through cycle 6. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must be >18 years of age
- Histologic diagnosis of AL amyloidosis
- Genetic testing must be negative for transthyretin mutations
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Patients should have received at least one line with an alkylating agent and/or a proteasome inhibitor and dexamethasone and not be in VGPR or CR at the time of inclusion
Key exclusion criteria (19 listed)
- Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura as the only evidence of disease. The finding of isolated vascular amyloid in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis
- Isolated soft tissue involvement
- Presence of non-AL amyloidosis
- Bone marrow plasma cells >30% on bone marrow aspirate at screening
- Cardiac mayo stage IIIb disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daratumumab | Drug | Daratumumab |
Primary outcome
Overall Response Rate
Time frame: After 6 cycles treatment (6 months).
Overall Response Rate (CR+VGPR) at the completion of 6 cycles of Daratumumab using the new response criteria (J Clin Oncol, 2012. 30(36): p. 4541-9.
1 secondary outcome
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03.
Time frame: Every month during 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daratumumab in people with Amyloidosis, run by University Hospital, Limoges at 10 sites in 2 countries.
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 13 inclusion and 19 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 9 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France, 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall Response Rate (time frame: After 6 cycles treatment (6 months).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jul 2021.