MCLA-117 in Acute Myelogenous Leukemia
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|ClinicalTrials.gov Identifier: NCT03038230|
Recruitment Status : Recruiting
First Posted : January 31, 2017
Last Update Posted : February 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|Acute Myelogenous Leukemia Acute Myeloid Leukemia||Drug: MCLA-117 bispecific antibody||Phase 1|
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) with relapse or refractory disease and newly diagnosed elderly untreated AML patients.
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 at least 15 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 7 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 Additional sites may be added to ensure there is an acceptable enrollment rate or to replace non-enrolling/withdrawn sites.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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Multinational Study of MCLA-117 in Acute Myelogenous Leukemia|
|Study Start Date :||April 2016|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Experimental: MCLA-117 bispecific antibody
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.
Drug: MCLA-117 bispecific antibody
MCLA-117, a human bispecific IgG antibody which targets CLEC12A and CD3
- 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
- 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 ]Maximum plasma concentration [Cmax] as measured from all individual plasma concentrations
- 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 ]Clearance of plasma
- 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 ]Volume of distribution at steady state [Vss]
- 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 ]Time to reach maximum plasma concentration [Tmax]
- 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 ]Half-life [t1/2] calculated as time from all individual plasma concentrations to reach 50% of maximum concentration
- Area under the concentration versus time curve from time zero to time t [AUC0-t] [ Time Frame: 1 week ]Area under the concentration versus time curve [AUC0-t]
- Incidence of AntiDrugAntibodies (ADA) against MCLA-117 [ Time Frame: 24 months ]Number of participants with ADAs against MCLA-117 as measured in serum
- Serum titer of ADAs against MCLA-117 [ Time Frame: Day 1 of each cycle ]Serum titer of ADAs against MCLA-117 as measured in serum
- Serum titer of ADAs against MCLA-117 [ Time Frame: Day 28 of each cycle ]Serum titer of ADAs against MCLA-117 as measured in serum
- Cytokine levels [ Time Frame: Cycle 1: Day 1, 4, 8 and 28 at predose, 4h and 24h after end of infusion ]Change in profile of cytokine upon administration of MCLA-117 compared to baseline
- Number of myeloblasts [ Time Frame: Day 1 of every cycle and through study completion, an average of 2 months ]number of blasts in peripheral blood and in bone marrow
- Objective response [ Time Frame: Day 1 of every cycle and through study completion, an average of 2 months ]Objective response is assessed by Cheson 2003
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03038230
|Contact: Ernesto Wasserman, MDfirstname.lastname@example.org|
|Contact: Andres Sirulnik, MD, PhDemail@example.com|
|Ziekenhuis Netwerk Antwerpen Campus Stuivenberg||Recruiting|
|Antwerpen, Belgium, 2060|
|Principal Investigator: Dimitri A Breems, MD|
|Institut Gustave Roussy||Recruiting|
|Villejuif Cedex, Ile-de-France, France, 94805|
|Contact: Elodie Zedouard|
|Principal Investigator: Stéphane De Botton, MD|
|Fondazione Policlinico Tor Vergata||Recruiting|
|Rome, Italy, 00133|
|Contact: Silvia Miccichè +390620903213 firstname.lastname@example.org|
|Principal Investigator: Adriano Venditti, MD|
|Vrije Universiteit Medisch Centrum||Recruiting|
|Amsterdam, Noord-Holland, Netherlands, 1081HV|
|Contact: Tanya Roosma +310204442258 email@example.com|
|Principal Investigator: Gert Ossenkoppele, MD|
|Erasmus MC||Not yet recruiting|
|Rotterdam, Zuid-Holland, Netherlands|
|Contact: Mojca Jongen-Lavrencic, M.D. +31107041367 firstname.lastname@example.org|
|Contact: Sarah Lonergan email@example.com|
|Principal Investigator:||Jorge Cortes, MD, PhD||Independent Protocol Advisor|