Tafasitamab (MOR00208) in Pediatric Patients With Relapsed or Refractory Acute B Lineage Leukemia (Anti-CD19-ALL)
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|ClinicalTrials.gov Identifier: NCT05366218|
Recruitment Status : Recruiting
First Posted : May 9, 2022
Last Update Posted : July 27, 2023
The objective of the trial is to evaluate the safety, clinical toxicity and in vivo immunological effects of MOR00208 in pediatric patients with acute lymphoblastic leukemia who showed newly emerging or persistent MRD after a first stem cell transplantation, received stem cell transplantation without having reached a sufficient molecular remission prior to transplant (defined as MRD ≥10E-4) irrespective of MRD after SCT or underwent a second or subsequent stem cell transplantation irrespective of MRD after SCT.
Part I: to determine the recommended dose of MOR00208 in pediatric patients Part II: to evaluate the time until hematological relapse or increase of MRD
|Condition or disease||Intervention/treatment||Phase|
|ALL, Childhood B-Cell Acute Lymphoid Leukemia Relapse Acute Lymphocytic Leukemia Refractory||Biological: Tafasitamab||Phase 1 Phase 2|
Acute lymphoblastic leukemia is the most common malignancy in children. In patients with > 2nd relapse or in patients who relapse after previous stem cell transplantation (SCT), conventional chemotherapy or even subsequent SCT results only in low probabilities for event free survival (1-year EFS ~30%) with a generally poor prognosis. Major cause of death is a subsequent relapse. To date there is no standard therapy available. The aim of this study is to establish an antibody approach as an additional therapy. Therefore, the safety and efficacy of the anti-CD19-antibody tafasitamab in such pediatric very high-risk patients will be evaluated. Patients will be included in the following stages of disease: newly emerging or persistent minimal residual disease (MRD) after a first SCT; SCT without having reached a sufficient molecular remission prior to transplant (defined as MRD ≥10E-4) irrespective of MRD after SCT; underwent a second or subsequent SCT irrespective of MRD after SCT. Tafasitamab will be used as a relapse prophylaxis as well as a treatment for patients with low detectable low MRD. The treatment is intended to reduce the likelihood of overt relapse after SCT in a collective of patients at highest risk of relapse, thereby improving the long-term survival of these patients. The bi-weekly application of anti-CD19-antibody has already shown promising results in compassionate use settings in pediatric patients. Furthermore, the safety of tafasitamab has already been analyzed in multiple studies in adults and has proven to be well tolerable. As a control group published data for these patient groups will be used with a combined 1-year EFS of 30% in which patients have been treated at the current standard of care.
The study consists of 2 parts:
The first part will evaluate safety along with the maximum tolerated dose of tafasitamab in pediatric patients. This will involve intra- and inter-individual dose escalation using pre-determined dose levels before the dose-finding phase is completed. If dose-limiting drug side effects occur during this dose-finding phase, additional patients will be included in the interindividual dose escalation until the maximum tolerated dose of tafasitamab is defined for the remainder of the study. For this dose-finding phase, a minimum of six and a maximum of 25 patients will be included.
Immediately thereafter, the second study phase begins, in which all patients from the dose-finding phase who have not experienced a dose-limiting toxicity, as well as additional enrolled patients, receive the defined maximum tolerated dose of tafasitamab. In this phase of the study, in addition to the continued recording of drug side effects, the efficacy of tafasitamab will be assessed using defined endpoints. A minimum evaluable number of 18 patients is planned for the assessment of these endpoints; to compensate for possible patient dropout during the study, recruitment of a minimum of 20 patients and a maximum of 39 patients, depending on the course of the dose-finding phase, is planned.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||A Prospective Phase I/II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy|
|Masking:||None (Open Label)|
|Official Title:||A Prospective Phase I/II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Tafasitamab (MOR00208) in Pediatric Patients With Relapsed or Refractory Acute B Lineage Leukemia|
|Actual Study Start Date :||March 8, 2023|
|Estimated Primary Completion Date :||March 2027|
|Estimated Study Completion Date :||March 2027|
All patients will receive MOR00208 over 2-3 hours i.v. MOR00208 will be administered on a bi-weekly (every fourteen days) basis with infusions on Days 1 and 15 of each 28-day cycle. Additional doses will be administered on Day 4, Day 8 and Day 22 of Cycle 1 as well as Day 8 and Day 22 of Cycle 2 and Cycle 3.
Other Name: MOR00208
- Primary endpoint Part I [ Time Frame: 49 days ]Determination of maximum tolerated dose of MOR00208 in pediatric patients
- Primary endpoint Part II [ Time Frame: 545 days ]Time until hematological relapse (> 5% leukemic blasts) or increase of MRD ≥ 2 log in bone marrow during an observation time of 545 days accounting for competing risks
- Pharmakokinetic of MOR00208 [ Time Frame: 8 days ]Mean plasma concentrations of MOR00208 will be calculated and displayed graphically
- Safety and toxicity of MOR00208 - Part I [ Time Frame: 49 days ]Adverse events will be presented in line listings and also in cumulative tabulations
- Treatment success [ Time Frame: 365 days ]Rate of patients with treatment success defined as survival without newly emerging MRD or increasing MRD ≥ 2 log in bone marrow or peripheral blood or unacceptable toxicity
- Overall survival [ Time Frame: 545 days ]OS from date of first dose until end of follow up at 545 days will be analyzed using Kaplan-Meier-Methods, presenting corresponding statistical parameters and 95% confidence limits and Kaplan-Meier survival curves. Patients alive at 545 days and patients that could not be followed up until 545 days but were seen alive at the last visit will be censored.
- MRD reduction [ Time Frame: 545 days ]The amount of patients with reduction of at least 1 log at any time point compared to baseline MRD measurement between SCT and start of study treatment will be calculated and displayed graphically. Rates and 95%-confidence limits are also provided.
- B cell numbers [ Time Frame: 545 days ]Mean B cell numbers will be calculated and displayed graphically with 95%-confidence limits.
- Cytotoxic lysis [ Time Frame: 545 days ]Cytotoxic lysis will be calculated and displayed graphically.
- Safety and toxicity of MOR00208 - Part II [ Time Frame: 545 days ]Adverse events will be presented in line listings and also in cumulative tabulations
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): NCT05366218
|Contact: Peter Lang, Prof.||0049 7071 firstname.lastname@example.org|
|Contact: Michael Abele, Dr.||0049 7071 email@example.com|
|Freiburg, Baden-Württemberg, Germany, 79106|
|Contact: Brigitte Strahm, Dr.|
|Contact: Carsten Speckmann, Dr.|
|University childrens Hospital||Recruiting|
|Tübingen, Baden-Württemberg, Germany, 72076|
|Contact: Peter Lang, Prof. Dr. 004970712984744 firstname.lastname@example.org|
|Contact: Michael Abele, Dr. 0049707184744 email@example.com|
|Klinik für Kinder- und Jugendmedizin||Recruiting|
|Ulm, Baden-Württemberg, Germany, 89070|
|Contact: Ansgar Schulz, Prof. Dr.|
|Contact: Manfred Hönig, Prof. Dr.|
|Klinikum Dr. von Haunersches Kinderspital||Not yet recruiting|
|München, Bayern, Germany, 80337|
|Contact: Tobias Feuchtinger, Prof. Dr.|
|Contact: Semjon Willer, Dr.|
|Düsseldorf, Nordrhein-Westfalen, Germany, 40225|
|Contact: Roland Meisel, Prof. Dr.|
|Contact: Sujal Ghosh, Dr.|
|Universitätsmedizin Berlin, Campus Virchow Klinikum||Recruiting|
|Berlin, Germany, 13353|
|Contact: Sandra Cyrull, Dr.|
|Contact: Arend von Stackelberg, Dr.|
|Universitätsklinikum||Not yet recruiting|
|Essen, Germany, 45147|
|Contact: Stefan Schönberger, Dr.|
|Contact: Michaela Höfs, Dr.|
|Universitätsklinikum, Klinik für Kinder- und Jugendmedizin||Not yet recruiting|
|Frankfurt, Germany, 60590|
|Contact: Peter Bader, Prof.|
|Contact: Andrea Jarisch, Dr.|
|Zentrum für Geburtshilfe, Kinder- und Jugendmedizin||Recruiting|
|Hamburg, Germany, 20246|
|Contact: Ingo Müller, Prof. Dr.|
|Contact: Manon Quedeville, Dr.|
|Universitätsklinikum Schleswig-Holstein, Campus Kiel||Recruiting|
|Kiel, Germany, 24105|
|Contact: Gunnar Cario, Prof.|
|Contact: Vieth Simon, Prof.|
|Würzburg, Germany, 97080|
|Contact: Matthias Eyrich, Prof.|
|Contact: Paul-Gerhardt Schlegel, Prof.|
|Principal Investigator:||Peter Lang, Prof.||University Childrens Hospital Tübingen|