Relapsed or Refractory Haematological Malignancies - Some sort of blood cancer
Conditions
Interventions
Intravenous injection of AZD4573 with monitoring afterwards, patients divided
in different arms. Dose of IV injection modified in cohort-system as stated in
the protocol.
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling and analyses. 2. Men and women >=18 years of age 3. Patients with histologically confirmed, relapsed or refractory haematological malignancies, with at least one measurable lesion >= 1.5 cm and where in the opinion of the Investigator, a clinical trial is the best option for next treatment based on prior response and/or tolerability to standard of care, e.g., but not limited to: Arm A: o B-cell Non-Hodgkin lymphoma o T-cell Non-Hodgkin lymphoma o Small lymphocytic lymphoma (SLL) o Multiple myeloma (MM) , Arm B: o CLL (chronic lymphocytic leukaemia) o Richter*s syndrome o AML/secondary AML o ALL o High-risk myelodysplastic syndrome (MDS) (according to revised International prognostic scoring system IPSS- R) o CMML (chronic myelomonocytic leukaemia), NOTE: AML/ALL patients must have pathologically confirmed first or second relapsed or primary refractory AML using the World Health Organization (WHO) definition or European LeukemiaNet (ELN) recommendations. A bone marrow blast count of >5% will be sufficient in the appropriate setting of a patient with a prior diagnosis of AML/ALL. NOTE: AML patients with APL (acute promyelocytic leukaemia FAB subtype M3) will be excluded NOTE: Patients >70 years of age with untreated AML who are considered unfit for intensive treatment or who refuse intensive treatment, may be considered eligible for the study, upon consultation and agreement between the Sponsor and the Investigator. NOTE: Patients with DLBCL subtypes such as Richter's syndrome, Transformed Follicular Lymphoma, Primary Mediastinal Lymphoma and High-grade lymphomas [e.g. double-hit]) are also eligible to be included in the Cohort 2A DLBCL expansion. 4. Eastern Cooperative Oncology Group (ECOG) performance status of =1000 cells/mm3 (1.0 x 109/L) o Platelet count >=50,000 cells/mm3 (50 x 1
Exclusion criteria
Exclusion criteria: 1. Treatment with any of the following: o Any other chemotherapy, immunotherapy or anticancer agents, including investigational agents, within 2 weeks of the first dose of study treatment o Any haematopoietic growth factors (e.g., filgrastim [granulocyte colony-stimulating factor; G-CSF], sargramostin [granulocyte-macrophage colony-stimulating factor; GM-CSF]) within 7 days of the first dose of study drug or pegylated G-CSF (pegfilgrastim) or darbepoetin within 14 days of the first dose of study drug o Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment Any full-dose level anti-coagulation treatment sufficiently prior to treatment that INR is =2) o ventricular arrhythmias requiring continuous therapy o atrial fibrillation, which is uncontrolled o haemorrhagic or thrombotic stroke, including transient ischemic attacks or any other central nervous system bleeding 10. Hyperuricaemia >10 mg/dL. NOTE: If hyperuricaemia of any kind is present at screening, standard
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety parameters: Frequency, severity, and relationship to study drug of any treatment-emergent adverse events or abnormalities of laboratory tests; DLTs; vital signs; ECGs; serious adverse events (SAEs); and adverse events leading to discontinuation of study treatment. Pharmacokinetic parameters: The following PK sampling timepoints applies to those patients enrolled into Cohorts 2A/B and 3A/B: schedules can be found in protocol synopsis. The timing of these samples may be adjusted, dependent upon ongoing PK analysis and interpretation. PK parameters to be estimated include maximum concentration (Cmax), area under the curve (AUC), half-life clearance and volume of distribution. Additional parameters may be calculated as appropriate. Surplus plasma samples may be analysed for potential metabolites of AZD4573. The data from this sample analysis may be pooled and these data will be exploratory and the results of any analysis may not be available at the end of the study. The results of this analysis if undertaken may not be reported in the final clinical study report (CSR). For Cohorts 1-3, ECGs will be collected for central analysis according to the schedule below: • Screening (Single ECG only) • Cycles A-D and Cycle 1, Day 1 (triplicate ECGs): * Pre-dose (up to 2 hours prior to infusion) and 1, 2, 4, 7 (7 for Cohort 2 only), 8 (8 for Cohort 3 only), 10, and 24 hours (i.e., Day 2) after starting the infusion (triplicate ECG will only be taken at each dosing day during which a patient is receiving a dose to which the patient was not exposed to previously, otherwise single ECGs apply). • Cycles 2-8: On Day 1 of each cycle, within 30 minutes after the end of infusion (Single ECG only) • Safety-follow up visit (Single ECG only) Pharmacodynamic and Biomarker Parameters: Whole blood samples for immediate on-site peripheral blood mononuclear cell (PBMC) isolation will be collected from all patients at screening and Day 1 of each new dose (i.e | — |
Secondary
| Measure | Time frame |
|---|---|
| n.a. | — |
Countries
Netherlands
Outcome results
None listed