Multiple MyelomaPhase 2PREDATORNCT03697655
Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma
A Phase 2 study testing Daratumumab 20 MG/ML [Darzalex] in people with Multiple Myeloma, run by Polish Myeloma Consortium at 2 sites in Poland.
Trial summary
PREDATOR is a study investigating a role of preemptive daratumumab therapy for preclinical relapse or progression of multiple myeloma (MM). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Daratumumab 20 MG/ML [Darzalex]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 274 participants
- Where
- 2 sitesPoland
- Study dates
- 10 Dec 2018to Jul 2024
- 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 with diagnosed symptomatic MM who have completed one or two prior lines of therapy; single or tandem autologous stem cell transplant is not considered a separate line of therapy and is not mandatory; and have achieved at least PR to last line of therapy, and who experience asymptomatic biochemical progression not meeting criteria for SPR.
- Males and females ≥18 years of age.
- Life expectancy of more than 3 months.
- ECOG performance status of 0-2.
- Adequate hepatic function, with bilirubin ≤1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
- ANC ≥1.0 x 109/L, hemoglobin ≥8 g/dL, platelet count ≥75 x 109/L.
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- Calculated creatinine clearance (by Cockroft-Gault) ≥50 mL/min (this equation is as follows: Creatinine clearance in ml/min: (140 - age) x body weight (kg) / 72 x plasma creatinine (mg/dL); multiplied by 0.85 for women) or serum creatinine below 2 g/dL.
- Negative pregnancy test (serum βHCG) for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (≥ 24 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential.
- FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study.
- Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy.
- Voluntary written informed consent.
- Patients with diagnosed symptomatic MM who have completed one or two prior lines of therapy; single or tandem autologous stem cell transplant is not considered a separate line of therapy and is not mandatory; and have achieved CR with negative MRD to the last line of therapy and who remain in CR MRD negative. The last response assessment confirming CR MRD negative status based on assessment of bone marrow sample using flow cytometry with sensitivity of at least 10-5 needs to be performed not earlier than 3 months before inclusion to the study.
- Males and females ≥18 years of age.
- Life expectancy of more than 3 months.
- ECOG performance status of 0-2.
- Adequate hepatic function, with bilirubin ≤1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
- ANC ≥1.0 x 109/L, hemoglobin ≥8 g/dL, platelet count ≥75 x 109/L.
- Calculated creatinine clearance (by Cockroft-Gault) ≥50 mL/min (this equation is as follows: Creatinine clearance in ml/min: (140 - age) x body weight (kg) / 72 x plasma creatinine (mg/dL); multiplied by 0.85 for women) or serum creatinine below 2 g/dL.
- Negative pregnancy test (serum βHCG) for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (≥ 24 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential
- FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study.
- Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy.
- Voluntary written informed consent.
Who cannot join
- Potential subjects with evidence of progressive disease (CRAB symptoms) as per IMWG criteria.
- Patient with SPR - significant paraprotein relapse defined as doubling of the M-component in two consecutive measurements separated by < 2 months; or an increase in the absolute levels of serum M protein by 1g/dl, or urine M protein by 500mg /24h, or involved serum FLC level by 20mg/dl (plus an abnormal FLC ratio) in two consecutive measurements separated by < 2 months.
- Patients who have already started or received post-transplant maintenance or consolidation treatment.
- Subject has received daratumumab or other anti-CD38 therapies previously.
- Patients not able to tolerate daratumumab or required concomitant medication and procedures.
- Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
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- Known moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study).
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- Plasma cell leukemia.
- Waldenström's macroglobulinemia.
- CNS involvement.
- Pregnant or lactating females.
- Radiotherapy within 14 days before randomization. Seven days may be considered if to single area.
- Major surgery within 3 weeks prior to first dose. Kyfoplasty is not considered as a major surgery.
- Myocardial infarction within 3 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening.
- Patient who in investigator's opinion is unable to comply with the protocol requirements.
- Uncontrolled hypertension or diabetes.
- Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to enter the study.
- Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
- Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone.
- Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
- PREDATOR-MRD:
- Potential subjects with evidence of progressive disease (CRAB symptoms) as per IMWG criteria.
- Patient with SPR - significant paraprotein relapse defined as doubling of the M-component in two consecutive measurements separated by < 2 months; or an increase in the absolute levels of serum M protein by 1g/dl, or urine M protein by 500mg /24h, or involved serum FLC level by 20mg/dl (plus an abnormal FLC ratio) in two consecutive measurements separated by < 2 months.
- Patients who have already started or received post-transplant maintenance or consolidation treatment.
- Subject has received daratumumab or other anti-CD38 therapies previously.
- Patients not able to tolerate daratumumab or required concomitant medication and procedures.
- Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
- Known moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study).
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- Plasma cell leukemia.
- Waldenström's macroglobulinemia.
- CNS involvement.
- Pregnant or lactating females.
- Radiotherapy within 14 days before randomization. Seven days may be considered if to single area.
- Major surgery within 3 weeks prior to first dose. Kyfoplasty is not considered as a major surgery.
- Myocardial infarction within 3 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12- lead ECG during screening.
- Patient who in investigator's opinion is unable to comply with the protocol requirements.
- Uncontrolled hypertension or diabetes.
- Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to enter the study.
- Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
- Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone.
- Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
Trial locations and contacts
2 sites in 1 country.
Poland2 sites, 2 recruiting
- Recruiting
Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu; Oddział Hematologii i Transplantacji Szpiku
Poznan, Greater Poland Voivodeship, 60-569
Dominik Dytfeld, MD, PhD, +48 602464708, dytfeld@me.com
- Recruiting
Instytut Hematologii i Transfuzjologii
Warsaw, Masovian Voivodeship, 02-776
Krzysztof Jamroziak, MD, PhD, +48 22 349 64 78, k.m.jamroziak@gmail.com
About this study
Official title: Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma (PREDATOR)
PREDATOR is a study investigating a role of preemptive daratumumab therapy for preclinical relapse or progression of multiple myeloma (MM).
Read the detailed description
The study is composed of two phase 2 randomized multi-center substudies:
- PREDATOR-BR: to investigate the role of daratumumab in the setting of biochemical relapse
- PREDATOR-MRD: to investigate the role of daratumumab in minimal residual disease (MRD) reappearance
- Conditions
- Multiple Myeloma
- Being tested
- Daratumumab 20 MG/ML [Darzalex]
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daratumumab 20 MG/ML [Darzalex]Drug
Also called Darzalex
Daratumumab dose 16 mg/kg body weight to be administered as an IV infusion. treatment given until clinical progression or SPR but no longer than 73 weeks
| Study group | Role | What they receive |
|---|---|---|
| PREDATOR-BR Cohort A | Experimental | n=46, Daratumumab 20 MG/ML [Darzalex], 16 mg/kg body weight administered as an intravenous infusion Receives: Drug: Daratumumab 20 MG/ML [Darzalex] |
| PREDATOR-BR Cohort B | No intervention | n=46, Control Group, Observation (no treatment) |
| PREDATOR-MRD Cohort A | Experimental | n=59, Daratumumab 20 MG/ML [Darzalex], 16 mg/kg body weight administered as an intravenous infusion Receives: Drug: Daratumumab 20 MG/ML [Darzalex] |
| PREDATOR-MRD Cohort B | No intervention | n=59, Control Group, Observation (no treatment) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival (ESF)
To compare (EFS) between daratumumab arm and observation arm after randomization of patients with biochemical relapse of Multiple Myeloma and MRD reappearance in Multiple Myeloma
Measured: from randomization till the date of development clinical relapse or death from any cause; up to 129 weeks
Secondary outcomes (2)
Overall Response Rate
ORR as determined by Investigator evaluation, defined as the percentage of subjects achieving an objective response (i.e. partial response or better), using IMWG Consensus Panel 1 response criteria
Measured: from randomization till progression or death from any cause, up to 129 weeks
Overall Survival
To compare overall survival between arms
Measured: throughout the duration of the study, no longer than 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2018
- Study start10 Dec 2018
- Primary completionSep 2020 (estimated)
- Study completionJul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- treatment arm and control (observation) arm
- Masking
- None (open label)
- Enrolment
- 274 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Polish Myeloma Consortium
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen-Cilag Ltd., Bioscience, S.A.
- Responsible party
- Sponsor
- Investigators
- Krzysztof Jamroziak, MD, PhD, Principal investigator, Polish Myeloma Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03697655
- Sponsor's protocol ID
- PMC008
- Acronym
- PREDATOR
- Status last verified
- Jan 2019
- First submitted
- 20 Sep 2018
- Last updated
- 3 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma (PREDATOR)
- ClinicalTrials.gov ID
- NCT03697655
- Acronym / sponsor ID
- PREDATOR / PMC008
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 274 participants (estimated)
- Lead sponsor
- Polish Myeloma ConsortiumUniversity, hospital or other
- Collaborators
- Janssen-Cilag Ltd., Bioscience, S.A.
- Study start
- 10 Dec 2018 (actual)
- Primary completion
- Sep 2020 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 5 Oct 2018 (actual)
- 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.
PREDATOR is a study investigating a role of preemptive daratumumab therapy for preclinical relapse or progression of multiple myeloma (MM).
Detailed description
The study is composed of two phase 2 randomized multi-center substudies:
- PREDATOR-BR: to investigate the role of daratumumab in the setting of biochemical relapse
- PREDATOR-MRD: to investigate the role of daratumumab in minimal residual disease (MRD) reappearance
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- treatment arm and control (observation) arm
| Arm | Type | Receives |
|---|---|---|
| PREDATOR-BR Cohort A | Experimental | Drug: Daratumumab 20 MG/ML [Darzalex]n=46, Daratumumab 20 MG/ML [Darzalex], 16 mg/kg body weight administered as an intravenous infusion |
| PREDATOR-BR Cohort B | No intervention | –n=46, Control Group, Observation (no treatment) |
| PREDATOR-MRD Cohort A | Experimental | Drug: Daratumumab 20 MG/ML [Darzalex]n=59, Daratumumab 20 MG/ML [Darzalex], 16 mg/kg body weight administered as an intravenous infusion |
| PREDATOR-MRD Cohort B | No intervention | –n=59, Control Group, Observation (no treatment) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients with diagnosed symptomatic MM who have completed one or two prior lines of therapy; single or tandem autologous stem cell transplant is not considered a separate line of therapy and is not mandatory; and have achieved at least PR to last line of therapy, and who experience asymptomatic biochemical progression not meeting criteria for SPR.
- Males and females ≥18 years of age.
- Life expectancy of more than 3 months.
- ECOG performance status of 0-2.
- Adequate hepatic function, with bilirubin ≤1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
Key exclusion criteria (45 listed)
- Potential subjects with evidence of progressive disease (CRAB symptoms) as per IMWG criteria.
- Patient with SPR - significant paraprotein relapse defined as doubling of the M-component in two consecutive measurements separated by < 2 months; or an increase in the absolute levels of serum M protein by 1g/dl, or urine M protein by 500mg /24h, or involved serum FLC level by 20mg/dl (plus an abnormal FLC ratio) in two consecutive measurements separated by < 2 months.
- Patients who have already started or received post-transplant maintenance or consolidation treatment.
- Subject has received daratumumab or other anti-CD38 therapies previously.
- Patients not able to tolerate daratumumab or required concomitant medication and procedures.
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 20 MG/ML [Darzalex]Also: DarzalexDaratumumab dose 16 mg/kg body weight to be administered as an IV infusion. treatment given until clinical progression or SPR but no longer than 73 weeks | Drug | PREDATOR-BR Cohort A, PREDATOR-MRD Cohort A |
Primary outcome
Event Free Survival (ESF)
Time frame: from randomization till the date of development clinical relapse or death from any cause; up to 129 weeks
To compare (EFS) between daratumumab arm and observation arm after randomization of patients with biochemical relapse of Multiple Myeloma and MRD reappearance in Multiple Myeloma
2 secondary outcomes
Overall Response Rate
Time frame: from randomization till progression or death from any cause, up to 129 weeks
Overall Survival
Time frame: throughout the duration of the study, no longer than 6 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2019.
- Individual participant dataSharing planned: No
Related trials for Multiple Myeloma
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Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
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Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
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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.
Krzysztof Jamroziak, MD, PhD principal investigator
Polish Myeloma Consortium
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daratumumab 20 MG/ML [Darzalex] in people with Multiple Myeloma, run by Polish Myeloma Consortium at 2 sites in Poland.
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 22 inclusion and 45 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: status not confirmed, as of the sponsor's last update on 3 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Poland. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Krzysztof Jamroziak, MD, PhD (+48 504 065 262, k.m.jamroziak@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event Free Survival (ESF) (time frame: from randomization till the date of development clinical relapse or death from any cause; up to 129 weeks). 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 3 Jan 2019.