Phase 2
Completed N=3
WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome
Chronic myelomonocytic leukemia · Myelodysplastic Syndrome With Isolated Del(5q) · Myelodysplastic/Myeloproliferative Neoplasm · Previously Treated Myelodysplastic Syndrome
Source: ClinicalTrials.gov NCT02666950 ↗
Enrolled (actual)
3
Serious AEs
100.0%
Results posted
Sep 2019
Primary outcomePrimary: Complete Response Rate (CR or CRi) Per the National Comprehensive Cancer Network (NCCN) Guidelines or According to Specific Criteria From Expert Panels — 0 percentage of patients
Summary
This randomized phase II trial studies how well WEE1 inhibitor AZD1775 with or without cytarabine works in treating patients with acute myeloid leukemia or myelodysplastic syndrome that has spread to other places in the body and usually cannot be cured or controlled with treatment. WEE1 inhibitor AZD1775 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving WEE1 inhibitor AZD1775 works better with or without cytarabine in treating patients with advanced acute myeloid leukemia or myelodysplastic syndrome.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Complete Response Rate (CR or CRi) Per the National Comprehensive Cancer Network (NCCN) Guidelines or According to Specific Criteria From Expert Panels |
— | — |
| SECONDARY Clinical Benefit as Measured by the Number of Patients Who Were Not RBC Transfusion-dependent Post-Baseline |
— | — |
| SECONDARY Duration of Response |
— | — |
| SECONDARY Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment |
100 | — |
| SECONDARY Overall Survival |
6 | — |
| SECONDARY Time to Progression, Defined as the Time From Registration to the Earliest Date of Documentation of Disease Progression |
3.9 | — |
| SECONDARY Time to Response, Defined as the Time From Registration to the Earliest Date of Documentation of Response |
— | — |
Eligibility Criteria
Inclusion Criteria
- Patient population (histological or cytologically confirmed diagnosis):
- Untreated elderly (> 60 years) AML if in the intermediate and poor-risk cytogenetic group and not candidates (as judged by treating doctor of medicine [MD]) for or willing to undergo standard induction therapy (i.e. elderly unfavorable cytogenetic AML) or any untreated AML age > 65 years
- Note: previous therapy with a hypomethylating agent (HMA) for a diagnosis of MDS is allowed
- 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 lenalidomide in addition to having failed or been intolerant to HMA treatment
- Note: patients with chronic myelomonocytic leukemia (CMML) and MDS/myeloproliferative neoplasms (MPN) overlap are allowed if meeting other study eligibility criteria
- Note: for all patient groups, therapy as part of a plan as a bridge to transplant is allowed
- Total bilirubin = 30 ml/min
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- 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 = 60 days from stem cell infusion, have graft-versus-host disease (GVHD) = 28 days at time of registration
Exclusion Criteria
- Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, known positive for active infectious hepatitis, type A, B or C (past infection allowed), or psychiatric illness/social situations that would limit compliance with study requirements; Note: ongoing infection controlled on antibiotics/antifungal/antiviral medications are allowed
- Any of the following prior therapies:
- Cytotoxic chemotherapy = 24 hours (hrs) before starting therapy; NOTE: hydroxyurea (HU) is allowed for blast count control throughout study
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm = 470 msec (as calculated per institutional standards) at study entry or congenital long QT syndrome
Data sourced from ClinicalTrials.gov (NCT02666950). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.