Tafasitamab (MOR00208) in Pediatric Patients With Relapsed or Refractory Acute B Lineage Leukemia

Acute Lymphocytic Leukemia Refractory, Acute Lymphoid Leukemia Relapse, ALL, Childhood B-Cell

CD19 positive, refractory to standard treatment, relapse

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

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.

Germany