A phase I, dose escalation study of S80880, a CD123 x CD3 *Dual Affinity Re-Targeting (DART)* bi-specific antibody-based molecule given as monotherapy in patients with acute leukaemias and other haematological malignancies expressing CD123
- Conditions
- haematological maligancyacute leukemias and myelodysplastic syndrome10024324
- Registration Number
- NL-OMON42264
- Lead Sponsor
- Institut de Recherches Internationales Servier I.R.I.S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 8
- male or female > or <= 18 years
- Patients with cytologically confirmed and documented primary or secondary acute myeloid leukaemia (AML) without established therapeutic alternatives or when established therapeutic alternatives are ineffective, poorly tolerated or unacceptable for the patient:
- In newly diagnosed patients * 70 years not eligible for cytotoxic chemotherapy or
- in patients with relapsed or refractory disease who have failed conventional therapy after at
least 1 line of treatment and who are not eligible for salvage therapy;
In following patients, in case established therapeutic alternatives are not available or when established therapeutic alternatives are ineffective, poorly tolerated or unacceptable for the patient:
- cytologically confirmed and documented relapsed/refractory B-cell acute lymphoid leukaemia (B-ALL),
- cytologically confirmed and documented relapsed/refractory Acute Leukaemia of Ambiguous Lineage (ALAL)
- patients with intermediate -2 of high risk myelodysplastic syndrome (MDS)
- cytologically and histologically confirmed relapsed/refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN);- Circulating white blood cells * 20 000/mm3,
- Adequate hepatic and renal function
- life expectancy > or <= 4 weeks
- ECOG (Eastern Cooperative Oncology Group) performance status < or <= 2
Diagnosis of myeloid sarcoma,
History of other malignancy within 3 years prior to start of protocol-specified therapy (exceptions: see protocol)
Patients who have not recovered from toxicity of previous antileukaemic therapy, including grade * 2 non-haematologic toxicity, prior to starting the test drug,
Patients previously treated by anti-CD123 therapy,
Any previous anticancer treatment for leukaemic disease within at least 2 weeks,
Previous radiotherapy or immunotherapy in the 4 weeks prior to first IMP intake,
Patients with previous history of allogeneic stem cell transplantation;
Any prior history of or suspected current autoimmune disorders (exceptions: see protocol),
Severe uncontrolled fungal, bacterial or viral infection,
Leukaemic central nervous system involvement,
Pregnant or breastfeeding women,
known hypersensitivity to murine or recombinant proteins, polysorbate 80, recombinant human serum albumin, benzyl alcohol or any excipient contained in the S80880 drug formulation, history of Quincke oedema,
Known infection with human immunodeficiency virus (HIV), infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive),
Any other diseases (e.g. adrenal insufficiency, malabsorption syndromes, metabolic dysfunction, physical examination finding), or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk for test drug complications.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The Primary endpoint is occurance of DLT (dose limiting toxicity) during cycle<br /><br>1.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary end points:<br /><br>Safety profile of S80880 assessed by:<br /><br>* All adverse events<br /><br>* All serious adverse events<br /><br>* Laboratory tests (haematology, blood biochemistry, coagulation, urinary<br /><br>analysis, pregnancy test)<br /><br>* Vital signs and performance status<br /><br>* Clinical examination<br /><br>* ECG parameters, cardiac function assessment<br /><br>PK profile parameters of S80880 in serum<br /><br>Response rate (any CR, PR or HI) as determined by investigator, using the<br /><br>response criteria proposed by the International working Group for MDS, using<br /><br>adapted criteria proposed by the International working Group for AML, B-ALL,<br /><br>ALAL and BPDCN,<br /><br>- Response duration,<br /><br>- Event-free survival,<br /><br>- Overall survival.</p><br>