Last updated on October 2018

Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL


Brief description of study

The purpose of the study is to determine the maximum tolerated dose (MTD) in patients with acute lymphoblastic leukemia (ALL) and to determine the safety and tolerability of increasing doses and different infusion times of AFM11 infusion in patients with adult B-precursor ALL

Detailed Study Description

Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia characterized by an overproduction of lymphoblasts or lymphocytes in the bone marrow and the peripheral blood; it is frequently accompanied by suppression of normal hematopoiesis. It can spread to the lymph nodes, spleen, liver, the central nervous system (CNS), and other organs (sanctuary sites). Without treatment, ALL usually progresses quickly.

B- and T-cell lymphoblastic leukemia cells express surface antigens that parallel their respective developmental lineages. Precursor B-cell ALL cells typically express CD10, CD19, and CD34 on their surface, along with nuclear terminal deoxynucleotide transferase. About 20% of adult ALL patients have a cytogenetic abnormality that is indistinguishable from the Philadelphia chromosome (Ph1, t(9;22)), according to the National Cancer Institute (NCI).

The rationale for the use of AFM11 is based on its ability to bind to both malignant cells via its anti-CD19 domain and to T-cells via its anti-CD3 domains. This results in the formation of the "immunological synapse" and the subsequent T-cell activation on leading to killing of malignant cells. AFM11 has 2 binding sites for CD19 and 2 for CD3, its molecular weight is ~ 105kDa compared to diabodies like blinatumomab with one binding site for each target and a much lower molecular weight ~ 55kDa. In addition, preclinical experiments have shown that AFM11 has about a 100 fold higher affinity to CD3 compared to diabodies and is inducing higher cytotoxicity in vitro in the presence of low effector:target cell ratios. These differences might allow for a shortening of the infusion times and potentially higher clinical efficacy compared to blinatumomab.

Clinical Study Identifier: NCT02848911

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Sandra Schmich

LKH-Universit tsklinikum Graz
Graz, Austria

Sandra Schmich

Kepler Universit tsklinikum Linz
Linz, Austria

Sandra Schmich

Uniklinikum Salzburg
Salzburg, Austria

Sandra Schmich

University Hospital
Brno, Czechia

Sandra Schmich

Rambam Medical Center
Haifa, Israel

Sandra Schmich

Hadassah Medical Center
Jerusalem, Israel

Sandra Schmich

Rabin Medical Center
Petah-Tikva, Israel

Sandra Schmich

Independent Public Healthcare Municipal Hospital
Chorzow, Poland

Sandra Schmich

University Hospital
Krakow, Poland

Sandra Schmich

Baranov Republican Hospital
Petrozavodsk, Russian Federation

Sandra Schmich

First Pavlov State Medical University
St. Petersburg, Russian Federation

Sandra Schmich

Almazov NW Federal Medical Research Center
St. Petersburg, Russian Federation