Acute Lymphoblastic LeukemiaPhase 1NCT04524455
Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL
A Phase 1 study testing Blinatumomab, AMG 404 and Dexamethasone Premedication in people with Acute Lymphoblastic Leukemia, run by Amgen at 19 sites in 9 countries.
Trial summary
The primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV)… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- Blinatumomab, AMG 404 and Dexamethasone Premedication
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 19 sitesin 9 countries
- Study dates
- 2 Oct 2020to 24 Jan 2023
- Phase
- Phase 1
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years at enrollment.
- Greater than or equal to 5% blasts in the bone marrow.
- Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2.
- Negative pregnancy test in women of childbearing potential.
Who cannot join
- Cancer chemotherapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy) within 14 days prior to study Day 1.
- Known hypersensitivity to blinatumomab or AMG 404 or to any component of the product formulation.
Trial locations and contacts
19 sites in 9 countries.
19 sites in 9 countries
United States5 sites
University of Chicago
Chicago, Illinois, 60637
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
City of Hope National Medical Center
Duarte, California, 91010
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Germany3 sites
Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universität Frankfurt am Main
Frankfurt am Main, 60590
Universitätsklinikum Schleswig-Holstein
Kiel, 24105
Universitaetsklinikum Regensburg
Regensburg, 93053
Australia2 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
The Royal Melbourne Hospital
Parkville, Victoria, 3050
France2 sites
Hôpital Saint Louis
Paris, 75010
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69645
Italy2 sites
Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola Malpighi
Bologna, 40138
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Brescia, 25123
Spain2 sites
Hospital Universitari Germans Trias i Pujol
Badalona, Catalonia, 08916
Hospital Clinic i Provincial de Barcelona
Barcelona, Catalonia, 08036
Netherlands1 site
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
About this study
Official title: A Phase 1b Open-label Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Administration of Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (ALL)
The primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV) blinatumomab.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- Blinatumomab, AMG 404, Dexamethasone Premedication
- Keywords
- Blinatumomab, AMG 404, Leukemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BlinatumomabDrug
Also called Blincyto
Blinatumomab will be administered as a continuous intravenous infusion (cIV).
AMG 404Drug
AMG 404 will be administered as an intravenous infusion (IV).
Dexamethasone PremedicationDrug
Dexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed.
| Study group | Role | What they receive |
|---|---|---|
| Blinatumomab and AMG 404 | Experimental | Not described Receives: Drug: Blinatumomab; Drug: AMG 404; Drug: Dexamethasone Premedication |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Investigators determined whether an adverse event (AE) qualified as a DLT per pre-specified protocol defined criteria. An AE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment.
Measured: Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days
Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs)
A TEAE was defined as any AE starting on or after first dose of blinatumomab or AMG 404. The investigator used clinical judgment to assess causal relationship. A serious AE (SAE) was defined as any AE that:
- results in death,
- immediately life-threatening,
- requires in-patient hospitalization or prolongation of existing hospitalization,
- results in persistent or significant disability/incapacity,
- is a congenital anomaly/birth defect, and/or
- other medically important serious AE.
AEs of interest (EOIs) for blinatumomab included capillary leak syndrome, cytokine release syndrome, decreased immunoglobulins, elevated liver enzyme, embolic and thrombotic events, immunogenicity, infections, infusion reactions without considering duration, leukoencephalopathy, progressive multifocal leukoencephalopathy, neurologic events, neutropenia and febrile neutropenia, pancreatitis, and tumor lysis syndrome. EOIs for AMG 404 included non-infectious diarrhea and hemorrhages.
Measured: Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days
Secondary outcomes (10)
Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)
Hematological remissions were defined by the following criteria:
CR:
- Less than 5% blasts in the bone marrow (BM)
- No evidence of disease
- Full recovery of peripheral blood (PB) counts:
- Platelets > 100 000/μl
- Absolute neutrophil count (ANC) > 1000/μl
CR with only CRh:
- Less than 5% blasts in the BM
- No evidence of disease
- Partial recovery of PB counts:
- Platelets > 50 000/μl and
- ANC > 500/μl
Percentage of participants with CR/CRh were summarized along with corresponding 95% exact confidence interval (CI) using the Clopper-Pearson method.
Measured: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
Percentage of Participants Who Achieved CR
Hematological remissions were defined by the following criteria:
CR:
- Less than 5% blasts in the BM
- No evidence of disease
- Full recovery of PB counts:
- Platelets > 100 000/μl
- ANC > 1000/μl
Percentage of participants with CR were summarized along with corresponding 95% exact CI using the Clopper-Pearson method.
Measured: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles
Duration of CR was calculated from the date CR was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR to event/censor date, divided by 30.5.
Median time to event and 95% CI was summarized using the Kaplan-Meier (KM) method.
Measured: Up to approximately 274 days
Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles
Duration of CR/CRh was calculated from the date CR/CRh was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR/CRh to event/censor date, divided by 30.5.
Median time to event and 95% CI was summarized using the KM method.
Measured: Up to approximately 274 days
Steady-state Concentrations (Css) of Blinatumomab
Pharmacokinetic (PK) parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Measured: Cohort 1: C1D1 and D8 (predose, 2 to 24 h postdose), and D11, D18 and D29; C2D1 (predose, 2 to 24 h postdose) and D29. Cohort 2a: C1D3 and D10 (predose, 2 to 48 h postdose), and D29, D30 and D31; C2D1 (predose, 2 to 24 h postdose), D13 and D29
Maximum Observed Concentration (Cmax) of AMG 404
PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Measured: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Time to Cmax (Tmax) of AMG 404
PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Measured: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404
PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.
Measured: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Number of Participants With Incidences of Anti-Blinatumomab Antibodies
Only samples testing positive for anti-blinatumomab binding antibodies were to be tested for neutralizing antibodies (NAbs) as pre-specified in the protocol.
Measured: Up to approximately 274 days
Number of Participants With Incidences of Anti-AMG 404 Antibodies
Only samples testing positive for anti-AMG 404 binding antibodies were to be tested for NAbs as pre-specified in the protocol.
Measured: Up to approximately 274 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2020
- Study start2 Oct 2020
- Primary completion24 Jan 2023
- Study completion24 Jan 2023
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.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by AmgenThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04524455
- Sponsor's protocol ID
- 20190177
- Status last verified
- Oct 2023
- First submitted
- 20 Aug 2020
- Last updated
- 8 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Open-label Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Administration of Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (ALL)
- ClinicalTrials.gov ID
- NCT04524455
- Acronym / sponsor ID
- 20190177
- Conditions
- Acute Lymphoblastic Leukemia
- Keywords
- Blinatumomab, AMG 404, Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 2 Oct 2020 (actual)
- Primary completion
- 24 Jan 2023 (actual)
- Study completion
- 24 Jan 2023 (actual)
- First posted
- 24 Aug 2020 (actual)
- Results
- Posted 8 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV) blinatumomab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blinatumomab and AMG 404 | Experimental | Drug: Blinatumomab, Drug: AMG 404, Drug: Dexamethasone Premedication |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years at enrollment.
- Greater than or equal to 5% blasts in the bone marrow.
- Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2.
- Negative pregnancy test in women of childbearing potential.
Key exclusion criteria (2 listed)
- Cancer chemotherapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy) within 14 days prior to study Day 1.
- Known hypersensitivity to blinatumomab or AMG 404 or to any component of the product formulation.
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 |
|---|---|---|
| BlinatumomabAlso: BlincytoBlinatumomab will be administered as a continuous intravenous infusion (cIV). | Drug | Blinatumomab and AMG 404 |
| AMG 404AMG 404 will be administered as an intravenous infusion (IV). | Drug | Blinatumomab and AMG 404 |
| Dexamethasone PremedicationDexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed. | Drug | Blinatumomab and AMG 404 |
Primary outcome
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time frame: Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days
Investigators determined whether an adverse event (AE) qualified as a DLT per pre-specified protocol defined criteria. An AE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment.
Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs)
Time frame: Median (min, max) overall duration from first dose until 30 days after last dose is: 83.4 (40.2, 274.1) days
A TEAE was defined as any AE starting on or after first dose of blinatumomab or AMG 404. The investigator used clinical judgment to assess causal relationship. A serious AE (SAE) was defined as any AE that: * results in death, * immediately life-threatening, * requires in-patient hospitalization or prolongation of existing hospitalization, * results in persistent or significant disability/incapacity, * is a congenital anomaly/birth defect, and/or * other medically important serious AE. AEs of interest (EOIs) for blinatumomab included capillary leak syndrome, cytokine release syndrome, decreased immunoglobulins, elevated liver enzyme, embolic and thrombotic events, immunogenicity, infections, infusion reactions without considering duration, leukoencephalopathy, progressive multifocal leukoencephalopathy, neurologic events, neutropenia and febrile neutropenia, pancreatitis, and tumor lysis syndrome. EOIs for AMG 404 included non-infectious diarrhea and hemorrhages.
10 secondary outcomes
Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)
Time frame: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
Percentage of Participants Who Achieved CR
Time frame: Within the first 2 cycles: Up to approximately 86 days; across all cycles: Up to approximately 274 days
Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles
Time frame: Up to approximately 274 days
Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles
Time frame: Up to approximately 274 days
Steady-state Concentrations (Css) of Blinatumomab
Time frame: Cohort 1: C1D1 and D8 (predose, 2 to 24 h postdose), and D11, D18 and D29; C2D1 (predose, 2 to 24 h postdose) and D29. Cohort 2a: C1D3 and D10 (predose, 2 to 48 h postdose), and D29, D30 and D31; C2D1 (predose, 2 to 24 h postdose), D13 and D29
Maximum Observed Concentration (Cmax) of AMG 404
Time frame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Time to Cmax (Tmax) of AMG 404
Time frame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404
Time frame: Cohort 1: C1D11 (predose, end of infusion to 48 h postdose), D18, D29, and D39 (predose and end of infusion). Cohort 2a: C1D1 (predose, end of infusion to 168 h postdose), D12 and D29 (predose and end of infusion)
Number of Participants With Incidences of Anti-Blinatumomab Antibodies
Time frame: Up to approximately 274 days
Number of Participants With Incidences of Anti-AMG 404 Antibodies
Time frame: Up to approximately 274 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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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.
MD study director
Amgen
19 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Blinatumomab, AMG 404 and Dexamethasone Premedication in people with Acute Lymphoblastic Leukemia, run by Amgen at 19 sites in 9 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 4 inclusion and 2 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 8 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Germany, Australia, France, Italy and 4 more countries. 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 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.
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 8 Apr 2024). 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?
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (time frame: Cohort 1: Up to 67 days; Cohort 2a: Up to 56 days). The study lists 2 primary outcomes in all. 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 8 Apr 2024.