The outcome of HMA-refractory patients with MDS or AML is dismal with a median survival of 5 months after failure, representing a significant unmet medical need due to the very limited treatment options. In this context, a specific targeting of the leukemic stem cell (LSC) seems a promising option to selectively combat the leukemic progenitor cells. In fact, CD123 is overexpressed in AML and MDS progenitors making it an attractive target for immunotherapy-based approaches. JNJ-56022473 is a promising compound that has been engineered with regard to this strategy and the current phase II trial has the aim to evaluate the overall hematological response rate at 3 months in HMA refractory/relapsed AML and MDS patients.
Name: JNJ-56022473
Description: JNJ-56022473 will be supplied as a lyophilized product containing 100mg of active pharmaceutical ingredient (50 mg/mL after reconstitution with 2.0 mL sterile water for injection). The JNJ-56022473 dose administered will be dependent upon the subject's weight at baseline. The JNJ-56022473 dose should be adjusted in case the subject's weight changes by > 10%. JNJ- 56022473 will be administered in 250 mL IV infusion over approximately 180 minutes using an infusion pump.Type: DrugTreatment Arm
Name: Bone marrow analyses and CBC with differential
Description: Bone marrow analyses and CBC with differential will be performed by a central laboratory. If the marrow cannot be aspirated, a biopsy should be performed.Type: ProcedureTreatment Arm
Name: Flow cytometry analyses
Description: Characterization of LSCs and blasts (including CD123 and CD38 expression) will be performed as study-related analyses in the context of this protocol by central flow cytometry using bone marrow samples.Type: OtherTreatment Arm
Name: Central biobanking
Description: Central biobanking of study samples (bone marrow, peripheral blood as well as a buccal swab) will be carried out in Dresden.Type: OtherTreatment Arm
Name: Histopathology analysis
Description: A bone marrow biopsy is taken whenever it seems necessary to the investigator.Type: ProcedureTreatment Arm
Name: Cytogenetic analysis
Description: The cytogenetic analysis with banding analysis (optional FISH) have to be performed at local labs. Therefore 2 - 5 ml of bone marrow will be collected and analysed.Type: GeneticTreatment Arm
Name: Serum chemistry
Description: For serum chemistry 15 ml (2 x 7,5 ml) of peripheral blood have to be collected.Type: ProcedureTreatment Arm
Name: Automated CBC
Description: For CBC a minimum of 3 ml of peripheral blood have to be collected.Type: ProcedureTreatment Arm
Name: Pregnancy Test
Description: Serum or urine pregnancy testing β-HCG with a sensitivity of at least 25 mIU/mL is to be done not more than 3 days prior to initiation of JNJ-56022473 in female patients with childbearing potential. Furthermore, serum or urine pregnancy testing has to be done after end of treatment (EoT) visit.Type: ProcedureTreatment Arm
Description: Overall hematological response rate at 3 months (either CR, PR, marrow-CR, HI, SD)
Measure: Overall hematological response rate Time: 3 monthsDescription: Toxicity as measured by NCI CTCAE 4.03
Measure: Toxicity Time: 3 or 12 monthsDescription: measured by EORTC-QLQ30
Measure: Quality of life EORTC-QLQ30 Time: 9 or 15 monthsSingle Group Assignment
There are 2 SNPs
To enhance the cytotoxicity of the first-generation antibody CSL360, the proprietary Xencor (Xmab®) technology was applied and two amino acid mutations (S239D and I332E) were introduced into the Fc region. --- S239D --- --- I332E ---
To enhance the cytotoxicity of the first-generation antibody CSL360, the proprietary Xencor (Xmab®) technology was applied and two amino acid mutations (S239D and I332E) were introduced into the Fc region. --- S239D ---