A Phase 1, Open-Label, Multicentre, Non-Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of AZD4573, a Potent and Selective CDK9 Inhibitor, in Subjects with Relapsed or Refractory Haematological Malignancies
- Conditions
- Relapsed or Refractory Haematological Malignancies - Some sort of blood cancer10025323
- Registration Number
- NL-OMON50684
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 13
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 <=2.
5. Must have received at least 2 prior lines of therapy for the treatment of
current histology and a clinical trial is best option for next treatment based
on prior response and/or tolerability to standard of care. Refer to National
Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology
(ESMO) guidelines of each respective histology for guidance. NOTE: For some
disease indications, for example Richter*s syndrome, failure of one therapy
(e.g., R-CHOP) would be sufficient to consider a patient for enrolment in a
study with an Investigational agent. Disease indications, where there may be no
standard of care or standard of care options have been exhausted after failure
of first line therapy, these patients may be discussed and considered by
Sponsor and Investigator on a case by case basis for enrolment into the study
and decisions to enrol such patients documented in writing.
6. Documented active disease requiring treatment per respective NCCN/ESMO
guideline that is relapsed or refractory defined as:
o Recurrence of disease after response to prior line(s) of therapy
o or progressive disease after completion of the treatment regimen preceding
entry into the study
7. Adequate haematologic function (Note: does not apply to acute leukaemias,
CLL, Richter*s syndrome or high-risk MDS), defined as:
o Absolute neutrophil count (ANC) >=1000 cells/mm3 (1.0 x 109/L)
o Platelet count >=50,000 cells/mm3 (50 x 1
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 <1.5 (DVT/PE prophylaxis dose is allowed)
o
2. Patients with asecetory mylema
3. With the exception of alopecia, any unresolved toxicities from prior therapy
greater than CTCAE Grade 1 at the time of starting study treatment.
4. Presence of, or history of, central nervous system (CNS) lymphoma,
leptomeningeal disease or spinal cord compression.
5. History of prior nonhaematologic malignancy except for the following:
o Malignancy treated with curative intent and with no evidence of active
disease present for more than 2 years before screening and felt to be at low
risk for recurrence by treating physician.
o Adequately treated lentigo maligna melanoma without current evidence of
disease or adequately controlled nonmelanomatous skin cancer.
o Adequately treated carcinoma in situ without current evidence of disease.
6. As judged by the Investigator, any evidence of severe or uncontrolled
systemic disease (e.g., severe hepatic impairment, interstitial lung disease
[bilateral, diffuse, parenchymal lung disease]), or current unstable or
uncompensated respiratory or cardiac conditions, or uncontrolled hypertension,
history of, or active, bleeding diatheses (e.g., hemophilia or von Willebrand
disease) or uncontrolled active systemic fungal, bacterial, viral, or other
infection (defined as exhibiting ongoing signs/symptoms related to the
infection and without improvement, despite appropriate antibiotics or other
treatment), or intravenous anti-infective treatment within 2 weeks before first
dose of study drug.
7. Known history of infection with human immunodeficiency virus (HIV).
8. Serological evidence of active Hepatitis B infection
9. Undergone any of the following procedures or experienced any of the
following conditions currently or in the preceding 6 months:
o coronary artery bypass graft
o angioplasty
o vascular stent - for the purposes of clarification, a patient who has had a
cardiac stent or arterial stent currently or in the preceding 6 months will not
be eligible for the study. However, a patient who has had a venous stent to
prevent life-threatening conditions, currently or in the preceding 6 months,
will be eligible for the study.
o myocardial infarction
o angina pectoris
o congestive heart failure (New York Heart Association Class >=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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method