- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03718143
AZD1775 in Advanced Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myelofibrosis
A Phase 2 Study of WEE1 Inhibition and AZD1775 Alone or Combined With Cytarabine in Patients With Advanced Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myelofibrosis
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10016
- NYU Langone Health
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion:
Inclusion Criteria
- Dose escalation part of trial for combined AraC + AZD1775 (Arm A)
- untreated elderly (>60 years) AML if in the poor-risk cytogenetic group (please reference Appendix V).
- untreated elderly (>60 years) AML if in the intermediate and poor-risk cytogenetic group (please reference Appendix V)
- relapsed or refractory AML (≥ 18 years)
- any MDS (≥ 18 years) having failed or been intolerant to prior hypomethylating agent (HMA) treatment.
- Failure is defined as any disease progression while on HMA, relapse after HMA treatment or no response after 4 cycles of 5-Azacitidine or decitabine
- Patients with isolated 5q-/5q- syndrome must have failed, not tolerated, or progressed on lenalidomide in addition to having failed or been intolerant to HMA treatment.
- advanced progressive MF, defined as intermediate and high risk primary and secondary MF, or any other MF failed or intolerant to JAK2 inhibitor therapy requiring medical therapy
- If appropriate, patients can have failed other prior therapies for their disease (i.e. JAK2 inhibitor, interferon, hydroxyurea or IMIDs). Patients may have failed more than one JAK2 inhibitor and JAK2 inhibitor must not have been the most recent treatment (e.g. other therapies as last therapy prior to study given after failure of previous JAK2 inhibitor).
- Failure/ intolerance of Ruxolitinib
- The following laboratory values obtained 7 days prior to registration.
- Total bilirubin ≤ 1.5 mg/dL (except Gilbert's syndrome or known hemolysis or leukemic infiltration)
- AST (SGOT) and ALT (SGPT) ≤ 2.5 x Upper Limit normal (ULN) or < 5 x ULN if organ involvement
- Alkaline Phosphatase < 5 x ULN - Serum creatinine ≤1.5 x ULN, or measured creatinine clearance (CrCl) ≥45 mL/min as calculated by the Cockcroft-Gault method (confirmation of creatinine clearance is only required when creatinine is >1.5 x institutional ULN) CrCl (glomerular filtration rate [GFR]) = (140-age) x (weight/kg) x Fa (72 x serum creatinine mg/dL) a where F= 0.85 for females and F=1 for males
- ECOG Performance Status (PS) 0, 1 (Appendix I).
- Ability to provide informed written consent and be able to adhere to the study visit schedule and other protocol requirements.
- Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
- Willing to provide blood and bone marrow aspirate samples for correlative research purposes
- Negative serum pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
- Female patients who are not of child-bearing potential and fertile females of childbearing potential
- Male patients should be willing to abstain or use barrier contraception (i.e., condoms) for the duration of the study drug exposure and for 3 months after study treatment discontinuation.
- Patients who have undergone stem cell transplantation (SCT), autologous or allogeneic, are eligible provided that they are > 60 days from stem cell infusion, have GVHD < grade 1 and are off immunosuppressive agents for > 28 days at time of registration.
Exclusion:
- AML patients who are suitable for and willing to receive intensive chemotherapy
Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Subject has had prescription or non-prescription drugs or other products known to be sensitive CYP3A4 substrates or CYP3A4 substrates
- The preferred azole anti-fungal medication is Fluconazole (alternatively Posaconazole) which can be given during treatment with AZD1775 (section 9.5).
- Pateints may not be on an inhibitor of BCRP as outlined in Appendix VI.
- Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study medication
- Mean resting corrected QTc interval using the Fridericia formula (QTcF) >450 msec/male and >470 msec/female (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome
- Herbal preparations/medications
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A: Elderly Newly diagnosed AML
Combination AZD1775 with AraC Elderly, newly diagnosed AML |
AZD1775 days 1-5 & 8-12 AraC days 1-5 & 8-12
|
Experimental: Arm B:Relapsed AML and MDS
Combination AZD1775 with AraC Relapsed/Refractory AML & HMA failure AML/ MDS |
AZD1775 days 1-5 & 8-12 AraC days 1-5 & 8-12
|
Active Comparator: Arm C: Relapsed AML, MDS and MF
AZD1775 only Relapsed/Refractory AML & HMA failure AML/ MDS and Relapsed/Refractory Primary & Secondary MF |
AZD1775 days 1-5 & 8-12
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete Remission (CR) Rate
Time Frame: 4 months
|
Less than 5% blasts in a non-hypocellular marrow with a granulocyte count ≥ 1.0, and a platelets count of ≥ 100 with complete resolution of extramedullary disease and absence of peripheral blood blasts.
|
4 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incomplete Measure of Complete Remission (CRi)
Time Frame: 4 months
|
is called if patient meets all CR criteria except for residual neutropenia (ANC<1 x109/L) or thrombocytopenia (platelets<100 x109/L)
|
4 months
|
Complete Cytogenetic Remission (CCyR)
Time Frame: 4 Months
|
The absence of chromosome abnormalities (if present at diagnosis) on conventional cytogenetic study using G-banding (at least 10 metaphases present).
|
4 Months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Precancerous Conditions
- Syndrome
- Myelodysplastic Syndromes
- Primary Myelofibrosis
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Preleukemia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Adavosertib
Other Study ID Numbers
- 17-01816
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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