Acute Myelogenous LeukemiaPhase 1NCT03038230
MCLA-117 in Acute Myelogenous Leukemia
A Phase 1 study testing MCLA-117 bispecific antibody in people with Acute Myelogenous Leukemia and Acute Myeloid Leukemia, run by Merus B.V. at 9 sites in 5 countries.
Trial summary
This is a First-in-Human, single arm, open-label, multi-national study designed to determine the safety, tolerability and preliminary efficacy of MCLA 117. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia, Acute Myeloid Leukemia
- What is being tested?
- MCLA-117 bispecific antibody
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 9 sitesin 5 countries
- Study dates
- Apr 2016to 11 May 2021
- Phase
- Phase 1
- 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
- Male or female age ≥18 years old;
- Signed informed consent form
- One of the two following:
- AML either de novo or secondary [any subtype except acute promyelocytic leukemia (APL)] who either:
- are in relapse to standard therapy following an initial response
- failed primary induction therapy with no CR (failed ≥2 courses of intensive induction therapy. Intensive chemotherapy defined as an intensity of ≥ 5+2)
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- newly diagnosed untreated AML in patients ≥ 65 years of age with high risk cytogenetics, if they are not candidates for standard available induction chemotherapy
- AML secondary to MDS, either relapsed or refractory, previously treated with hypomethylating agents for at least 4 cycles;
- Relapsed or refractory AML unfit for intensive chemotherapy previously treated with a low intensity regimen (e.g. low dose Ara-c, hypomethylating agent, etc.) including Venetoclax for at least 2 cycles;
- OR ii) MDS patients who meet the following criteria: very high-risk disease (IPSS-R score > 6, Greenberg et al., 2012), either relapsed or refractory, previously treated with hypomethylating agents for at least 4 cycles;
- Must have baseline BM sample taken by BMA/BMB within 28 days prior to first dose of MCLA-117 for CLEC12A detection;
- Estimated life expectancy of at least 8 weeks;
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
- Significant toxicities incurred as a result of previous anti-cancer therapy resolved to ≤ Grade 1 (NCI-CTCAE version 4.03);
- Acceptable laboratory values at screening;
- Male patients must agree to use an adequate and medically accepted method of contraception throughout the study and for at least 6 months after if their sexual partners are women of child bearing potential (WOCBP).
- WOCBP must be using highly effective and medically accepted method of contraception to avoid pregnancy throughout the study and for at least 6 months after the study ;
- WOCBP must have a negative serum or urine pregnancy test within 72 hours prior to the start of study drug.
- Peripheral blast count </= 30,000/mm3 at the time of initiation of infusion on Cycle 1 Day 1.
- Able and willing to comply with all study procedures.
Who cannot join
- Diagnosis of chronic myelogenous leukemia in blast crisis;
- Prior hematopoietic stem cell transplantation (this exclusion applies for dose escalation Part 1 and Cohort A of Part 2);
- For patients in Cohort B of Part 2, prior hematopoietic stem cell transplantation is allowed under certain circumstances.
- Treatment with anticancer medications, investigational drugs or radiotherapy is allowed within 2 weeks or 5 half-lives prior to start of MCLA-117;
- Previous receipt of live vaccines in the 4 weeks prior to study drug administration;
- Chronic concurrent need of use of corticosteroids > 10 mg/day of oral prednisone or the equivalent, except topical preparations (e.g., topical creams, steroid inhaler, nasal spray or ophthalmic solution);
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- Use of immunosuppressant medications within 4 weeks of MCLA-117 administration;
- Clinically active central nervous system (CNS) leukemia;
- Patients who are pregnant or lactating;
- Patients with an active infection or with an unexplained fever during screening or on the first scheduled day of dosing;
- Patients with known hypersensitivity to any of the components of MCLA-117 or who have had prior hypersensitivity reactions to human or humanized monoclonal antibodies;
- Patients with known HIV, hepatitis B or C;
- Patients with New York Heart Association Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%, or significant uncontrolled cardiac disease, current diagnosis of unstable angina, uncontrolled congestive heart failure, new myocardial infarction, or ventricular arrhythmia requiring medication;
- Prior malignancy (other than basal cell carcinoma and cervical in situ carcinoma) unless treated with a curative intend and without evidence of malignant disease for 1 year before screening. Patients with prior hematologic malignancies that have progressed to AML (such as Myelodysplastic syndrome, myeloproliferative neoplasms, bi-phenotypic leukemias, AcuteLymphocyticLeukemia) or AML that has relapsed are eligible;
- Urinary protein >2+ possibly indicative of renal disease. If the 24 hours urine protein shows a result of < 100 mg protein, subject can be eligible;
- Patients with any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results;
- WOCBP or males with a WOCB partners not willing to use highly effective and medically accepted methods of contraception for 6 months after last study drug administration.
- Need for concurrent other cytoreductive chemotherapy.
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
United States3 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Netherlands3 sites
Amsterdam UMC, location VUmc
Amsterdam, North Holland, 1081HV
Universitair Medisch Centrum Groningen
Groningen
Erasmus MC
Rotterdam, South Holland
About this study
Official title: A Phase 1, Multinational Study of MCLA-117 in Acute Myelogenous Leukemia
This is a First-in-Human, single arm, open-label, multi-national study designed to determine the safety, tolerability and preliminary efficacy of MCLA 117.
Read the detailed description
Study Design :
This open label, single arm, multinational, first-in-human study consists of 2 parts. Part 1 consists of dose escalation cohorts and Part 2 is a dose expansion cohort.
The study population will include adult AML patients (and all subtypes of AML, except for APL) with relapse or refractory disease and newly diagnosed elderly untreated AML patients with high risk cytogenetics. In addition, very high-risk MDS patients with relapsed or refractory disease are eligible.
In Part 1, dose escalations cohorts are followed until dose-limiting toxicity (DLT) or a maximum tolerated dose (MTD) or RecommendedPart2Dose (RP2D) is defined. Dose escalation decisions will be made by the Data Review Committee and will be primarily guided by safety data observed through the end of Cycle 1, as well as on-going assessment of safety beyond Cycle 1 in later cohorts.
Part 2 will begin once the MTD or RP2D is determined in Part 1. Part 2 will further characterize the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamic (PD), immunogenicity and to assess preliminary efficacy of MCLA-117. This part will enroll approximately 30 evaluable patients (defined as evaluable for first efficacy assessment).
For both parts, the study consists of 3 periods: a Screening period (up to 28 days prior to the first dose of study drug); a Treatment period (first dose of study drug until the last dose of study drug with treatment cycles of 28 days); and a Follow Up period (through 30 days after the last dose and quarterly checks for survival data for up to 1 year). Participants' safety will be monitored throughout the study. Patients will be permitted to receive MCLA-117 beyond Cycle 1 if conditions allow this.
Number of Sites:
Approximately 15 centers in five countries are estimated to be involved during Parts 1 and 2 of the study. Additional sites may be added to ensure there is an acceptable enrollment rate or to replace non-enrolling/withdrawn sites.
- Conditions
- Acute Myelogenous Leukemia, Acute Myeloid Leukemia
- Being tested
- MCLA-117 bispecific antibody
- Keywords
- human bispecific full length IgG antibody, CLEC12A, CD3, MCLA-117, First in Human, Antibodies, Bispecific, Immunologic Factors, relapsed, refractory patient, AML, minimal residual disease (MRD), Acute Myelogenous Leukemia, Acute Myeloid Leukemia, CD34+CD38, T-cell recruiting
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MCLA-117 bispecific antibodyDrug
Also called bispecific, human bispecific common light chain, bispecific IgG1 targeting CLEC12A and CD3
MCLA-117, a human bispecific IgG antibody which targets CLEC12A and CD3
| Study group | Role | What they receive |
|---|---|---|
| MCLA-117 bispecific antibody | Experimental | Dose escalation cohorts, with escalating doses of MCLA-117 until MTD or RP2D is reached. The dose is given weekly after initial ramp-up dosing steps. Each Cycle is 28 days. Single agent treatment.
Part 2-Expansion Cohort: The RP2D of MCLA-117 is given weekly after initial ramp-up dosing steps. Each Cycle is 28 days. Single agent treatment. Receives: Drug: MCLA-117 bispecific antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Dose Limiting Toxicities (DLT)
Evaluation of number of participants with treatment related toxicity observed during a dose escalation step for 1 Cycle
Measured: 28 days
Secondary outcomes (12)
Maximum plasma concentration [Cmax]
Maximum plasma concentration [Cmax] as measured from all individual plasma concentrations
Measured: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Clearance of plasma
Clearance of plasma
Measured: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Volume of distribution at steady state [Vss]
Volume of distribution at steady state [Vss]
Measured: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Time to reach maximum plasma concentration [Tmax]
Time to reach maximum plasma concentration [Tmax]
Measured: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Half-life [t1/2]
Half-life [t1/2] calculated as time from all individual plasma concentrations to reach 50% of maximum concentration
Measured: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Area under the concentration versus time curve from time zero to time t [AUC0-t]
Area under the concentration versus time curve [AUC0-t]
Measured: 1 week
Incidence of AntiDrugAntibodies (ADA) against MCLA-117
Number of participants with ADAs against MCLA-117 as measured in serum
Measured: 24 months
Serum titer of ADAs against MCLA-117
Serum titer of ADAs against MCLA-117 as measured in serum
Measured: Day 1 of each cycle
Serum titer of ADAs against MCLA-117
Serum titer of ADAs against MCLA-117 as measured in serum
Measured: Day 28 of each cycle
Cytokine levels
Change in profile of cytokine upon administration of MCLA-117 compared to baseline
Measured: Cycle 1: Day 1, 4, 8 and 28 at predose, 4h and 24h after end of infusion
Number of myeloblasts
number of blasts in peripheral blood and in bone marrow
Measured: Day 1 of every cycle and through study completion, an average of 2 months
Objective response
Objective response is assessed by Cheson 2003
Measured: Day 1 of every cycle and through study completion, an average of 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2017 (estimated)
- Study startApr 2016
- Primary completion11 May 2021
- Study completion11 May 2021
Why it stopped: strategic considerations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myelogenous LeukemiaStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merus B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jorge Cortes, MD, PhD, Principal investigator, Independent Protocol Advisor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03038230
- Sponsor's protocol ID
- MCLA-117-CL01
- Other IDs
- 2015-003704-23, 2015
- Status last verified
- Apr 2025
- First submitted
- 26 Jan 2017
- Last updated
- 6 Apr 2025
- 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 6 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multinational Study of MCLA-117 in Acute Myelogenous Leukemia
- ClinicalTrials.gov ID
- NCT03038230
- Acronym / sponsor ID
- MCLA-117-CL01
- Conditions
- Acute Myelogenous Leukemia, Acute Myeloid Leukemia
- Keywords
- human bispecific full length IgG antibody, CLEC12A, CD3, MCLA-117, First in Human, Antibodies, Bispecific, Immunologic Factors, relapsed, refractory patient, AML, minimal residual disease (MRD), Acute Myelogenous Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: strategic considerations
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Merus B.V.Industry (pharma, biotech, devices)
- Study start
- Apr 2016 (actual)
- Primary completion
- 11 May 2021 (actual)
- Study completion
- 11 May 2021 (actual)
- First posted
- 31 Jan 2017 (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 First-in-Human, single arm, open-label, multi-national study designed to determine the safety, tolerability and preliminary efficacy of MCLA 117.
Detailed description
Study Design :
This open label, single arm, multinational, first-in-human study consists of 2 parts. Part 1 consists of dose escalation cohorts and Part 2 is a dose expansion cohort.
The study population will include adult AML patients (and all subtypes of AML, except for APL) with relapse or refractory disease and newly diagnosed elderly untreated AML patients with high risk cytogenetics. In addition, very high-risk MDS patients with relapsed or refractory disease are eligible.
In Part 1, dose escalations cohorts are followed until dose-limiting toxicity (DLT) or a maximum tolerated dose (MTD) or RecommendedPart2Dose (RP2D) is defined. Dose escalation decisions will be made by the Data Review Committee and will be primarily guided by safety data observed through the end of Cycle 1, as well as on-going assessment of safety beyond Cycle 1 in later cohorts.
Part 2 will begin once the MTD or RP2D is determined in Part 1. Part 2 will further characterize the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamic (PD), immunogenicity and to assess preliminary efficacy of MCLA-117. This part will enroll approximately 30 evaluable patients (defined as evaluable for first efficacy assessment).
For both parts, the study consists of 3 periods: a Screening period (up to 28 days prior to the first dose of study drug); a Treatment period (first dose of study drug until the last dose of study drug with treatment cycles of 28 days); and a Follow Up period (through 30 days after the last dose and quarterly checks for survival data for up to 1 year). Participants' safety will be monitored throughout the study. Patients will be permitted to receive MCLA-117 beyond Cycle 1 if conditions allow this.
Number of Sites:
Approximately 15 centers in five countries are estimated to be involved during Parts 1 and 2 of the study. Additional sites may be added to ensure there is an acceptable enrollment rate or to replace non-enrolling/withdrawn sites.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MCLA-117 bispecific antibody | Experimental | Drug: MCLA-117 bispecific antibodyDose escalation cohorts, with escalating doses of MCLA-117 until MTD or RP2D is reached. The dose is given weekly after initial ramp-up dosing steps. Each Cycle is 28 days. Single agent treatment. Part 2-Expansion Cohort: The RP2D of MCLA-117 is given weekly after initial ramp-up dosing steps. Each Cycle is 28 days. Single agent treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Male or female age ≥18 years old;
- Signed informed consent form
- One of the two following:
- OR ii) MDS patients who meet the following criteria: very high-risk disease (IPSS-R score > 6, Greenberg et al., 2012), either relapsed or refractory, previously treated with hypomethylating agents for at least 4 cycles;
- Must have baseline BM sample taken by BMA/BMB within 28 days prior to first dose of MCLA-117 for CLEC12A detection;
Key exclusion criteria (18 listed)
- Diagnosis of chronic myelogenous leukemia in blast crisis;
- Prior hematopoietic stem cell transplantation (this exclusion applies for dose escalation Part 1 and Cohort A of Part 2);
- For patients in Cohort B of Part 2, prior hematopoietic stem cell transplantation is allowed under certain circumstances.
- Treatment with anticancer medications, investigational drugs or radiotherapy is allowed within 2 weeks or 5 half-lives prior to start of MCLA-117;
- Previous receipt of live vaccines in the 4 weeks prior to study drug administration;
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 |
|---|---|---|
| MCLA-117 bispecific antibodyAlso: bispecific, human bispecific common light chain, bispecific IgG1 targeting CLEC12A and CD3MCLA-117, a human bispecific IgG antibody which targets CLEC12A and CD3 | Drug | MCLA-117 bispecific antibody |
Primary outcome
Number of participants with Dose Limiting Toxicities (DLT)
Time frame: 28 days
Evaluation of number of participants with treatment related toxicity observed during a dose escalation step for 1 Cycle
12 secondary outcomes
Maximum plasma concentration [Cmax]
Time frame: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Clearance of plasma
Time frame: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Volume of distribution at steady state [Vss]
Time frame: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Time to reach maximum plasma concentration [Tmax]
Time frame: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Half-life [t1/2]
Time frame: Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Area under the concentration versus time curve from time zero to time t [AUC0-t]
Time frame: 1 week
Incidence of AntiDrugAntibodies (ADA) against MCLA-117
Time frame: 24 months
Serum titer of ADAs against MCLA-117
Time frame: Day 1 of each cycle
Serum titer of ADAs against MCLA-117
Time frame: Day 28 of each cycle
Cytokine levels
Time frame: Cycle 1: Day 1, 4, 8 and 28 at predose, 4h and 24h after end of infusion
Number of myeloblasts
Time frame: Day 1 of every cycle and through study completion, an average of 2 months
Objective response
Time frame: Day 1 of every cycle and through study completion, an average of 2 months
Results and safety
The study was stopped early (reason given: strategic considerations). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2025.
- 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.
Jorge Cortes, MD, PhD principal investigator
Independent Protocol Advisor
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MCLA-117 bispecific antibody in people with Acute Myelogenous Leukemia and Acute Myeloid Leukemia, run by Merus B.V. at 9 sites in 5 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 20 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: stopped early, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Netherlands, Belgium, 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 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?
The study was stopped early (reason given: strategic considerations). Results are not available in the source record.
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 with Dose Limiting Toxicities (DLT) (time frame: 28 days). 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 6 Apr 2025.