Treatment of acute lymphoblastic leukemia

Abstract

The present invention relates to a method for the treatment, amelioration or elimination of acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19xCD3 bispecific single chain antibody construct to an adult patient in the need thereof.

1 . A method for the treatment, amelioration or elimination of acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19×CD3 bispecific single chain antibody construct to an adult patient in the need thereof. 
     
     
         2 . The method of  claim 1 , wherein said acute lymphoblastic leukemia (ALL) is B-lineage acute lymphoblastic leukemia. 
     
     
         3 . The method of  claim 1 , wherein said acute lymphoblastic leukemia (ALL) is refractory to chemotherapy in patients non-eligible for allogeneic hematopoietic stem cell transplantation. 
     
     
         4 . The method of  claim 1 , followed by allogeneic hematopoietic stem cell transplantation or wherein said method replaces allogeneic hematopoietic stem cell transplantation in patients eligible for allogeneic hematopoietic stem cell transplantation. 
     
     
         5 . The method of  claim 1 , wherein the method is for the treatment, amelioration or elimination of minimal residual disease (MRD) in a patient with acute lymphoblastic leukemia (ALL). 
     
     
         6 . The method of  claim 5 , wherein said patient is MRD-positive in complete hematological remission. 
     
     
         7 . The method of  claim 5 , wherein the administration of said pharmaceutical composition results in stable disease or converts MRD positive acute lymphoblastic leukemia (ALL) into an MRD negative status. 
     
     
         8 . The method of  claim 5 , wherein MRD is measured with quantitative detection of individual rearrangements of immunoglobulin genes or T-cell receptor (TCR) rearrangements, or by bcr/abl fusion transcripts, or by t(4;11) translocations using PCR or FACS analysis. 
     
     
         9 . The method of  claim 8 , wherein the ALL patient shows a bcr/abl or a t(4;11) translocation signal above detection limit and/or at least one marker by rearrangement with a sensitivity of>10 −4 . 
     
     
         10 . The method of  claim 8 , wherein the time to molecular relapse detectable by the method is more than 4 months. 
     
     
         11 . The method of  claim 1 , wherein the corresponding variable heavy chain regions (V H ) and the corresponding variable light chain regions (V L ) regions in said CD19×CD3 bispecific single chain antibody construct are arranged, from N-terminus to C-terminus, in the order, V L (CD19)-V H (CD19)-V H (CD3)-V L (CD3). 
     
     
         12 . The method of  claim 11 , wherein said CD19×CD3 bispecific single chain antibody construct comprises an amino acid sequence as set forth in SEQ ID NO. 1. 
     
     
         13 . The method of  claim 1 , wherein one treatment cycle is a 4-week continuous infusion. 
     
     
         14 . The method of  claim 13 , wherein the treatment cycle is repeated at least three times, after determination of a MRD negative status (consolidation). 
     
     
         15 . The method of  claim 1 , wherein the CD19×CD3 bispecific single chain antibody construct is to be administered in a daily dose of 5 μg to 100 μg per square meter patient body surface area. 
     
     
         16 . The method of  claim 15 , wherein the CD19×CD3 bispecific single chain antibody construct is to be administered in a daily dose of 15 μg to 30 μg per square meter patient body surface area. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 2 , wherein said B-lineage acute lymphoblastic leukemia is B-precursor acute lymphoblastic leukemia. 
     
     
         19 . The method of  claim 11 , wherein said CD19×CD3 bispecific single chain antibody construct comprises an amino acid sequence at least 90% identical to SEQ ID NO. 1. 
     
     
         20 . The method of  claim 11 , wherein said CD19×CD3 bispecific single chain antibody construct comprises an amino acid sequence at least 95% identical to SEQ ID NO. 1. 
     
     
         21 . The method of  claim 13 , wherein the at least four weeks of continuous infusion is followed by at least a 2-week treatment-free interval. 
     
     
         22 . The method of  claim 14 , wherein each treatment cycle is followed by at least a 2-week treatment-free interval.