WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02666950
• Date of registration: 08/01/2016
• Prospective Registration: Yes
• Primary sponsor: Mayo Clinic
• Public title: WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome
• Scientific title: A Phase 2 Study of WEE1 Inhibition With AZD1775 Alone or Combined With Cytarabine in Patients With Advanced Acute Myeloid Leukemia and Myelodysplastic Syndrome
• Date of first enrolment: May 5, 2017
• Target sample size: 3
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02666950
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Raoul Tibes
• Affiliation: Mayo Clinic

Key inclusion & exclusion 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 =< 1.5 mg/dL (except Gilbert's syndrome or known hemolysis or leukemic
infiltration)

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
upper limit normal (ULN) or < 5 x ULN if organ involvement

- Alkaline phosphatase < 5 x ULN

- Serum creatinine =< 2 x ULN or 24 hour creatinine (Cr) clearance > 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 =< 7 days prior to registration, for women of
childbearing potential only

- Men and women must be willing to use appropriate contraception throughout study and
for 6 months after

- Male patients who are sexually active with a female partner of childbearing potential
must be either surgically sterilized or agree to use barrier contraception (ie,
condoms) for the duration of study participation, and for 90 days after the final dose
of study drug; cessation of birth control after this point should be discussed with a
responsible physician

- Patients who have undergone stem cell transplantation (SCT), autologous or allogeneic,
are eligible provided that they are > 60 days from stem cell infusion, have
graft-versus-host disease (GVHD) =< grade 1 and are off immunosuppressive agents for >
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 =<14 days prior to registration

- Immunotherapy =< 14 days prior to registration

- Biologic therapy (i.e. antibody therapies) =< 14 days prior to registration

- Radiation therapy =<14 days prior to registration

- Targeted therapies (i.e. kinase inhibitors, =< 7 days or 5 half-life's whichever
is shorter)

• For steroids or other non-cytotoxics given for blast count control, patient
must be off for > 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 =< 14 days prior to registration

- Active uncontrolled central nervous system (CNS) leukemia; NOTE: positive
(cyto)pathology is allowed and patient can receive intrathecal chemotherapy

- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
positive and currently receiving antiretroviral therapy; NOTE: patients known to be
HIV positive, but without clinical evidence of an immunocompromised state, are
eligible for this trial

- Any previous treatment with AZD1775 or allergic reactions to excipients of AZD1775

- Acute promyelocytic leukemia (APL, M3) unless failed regimens that included tretinoin,
arsenic trioxide, anthracyclines and cytarabine and currently NOT candidates for stem
cell transplantation

- Major surgery =< 28 days prior to registration

- Clinically significant heart disease, including the following:

- Active severe angina pectoris within 3 months prior to registration

- Acute myocardial infarction within 3 months prior to registration

- New York Heart Association classification IV cardiovascular disease or
symptomatic class III disease

- Note: patients with any of the above may be allowed after discussion amongst
the investigators including the principal investigator

- Any of the following:

- 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 cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) substrates or
CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong
inhibitors/inducers of CYP3A4 which cannot be discontinued two weeks prior
(alternatively 5 half lives if T1/2 is known) prior to day 1 of dosing and withheld
throughout the study until 2 weeks after the last dose of study drug

- NOTE: co-administration of aprepitant or fosaprepitant during this


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Myelodysplastic Syndrome With Isolated Del(5q)

Previously Treated Myelodysplastic Syndrome

Myelodysplastic/Myeloproliferative Neoplasm

Untreated Adult Acute Myeloid Leukemia

Chronic Myelomonocytic Leukemia

Recurrent Adult Acute Myeloid Leukemia

Intervention(s)

Other: Pharmacological Study

Other: Laboratory Biomarker Analysis

Drug: Cytarabine

Other: Questionnaire Administration

Other: Quality-of-Life Assessment

Drug: WEE1 Inhibitor AZD1775

Primary Outcome(s)

Complete Response Rate (CR or CRi) Per the National Comprehensive Cancer Network (NCCN) Guidelines or According to Specific Criteria From Expert Panels [Time Frame: Up to 17 months]

Secondary Outcome(s)

Clinical Benefit as Measured by the Number of Patients Who Were Not RBC Transfusion-dependent Post-Baseline [Time Frame: Up to 17 months]

Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment [Time Frame: Up to 30 days post-treatment]

Overall Survival [Time Frame: From registration to death due to any cause, assessed up to 17 months]

Time to Progression, Defined as the Time From Registration to the Earliest Date of Documentation of Disease Progression [Time Frame: Up to 17 months]

Duration of Response [Time Frame: Up to 17 months]

Time to Response, Defined as the Time From Registration to the Earliest Date of Documentation of Response [Time Frame: Up to 17 months]

Secondary ID(s)

P30CA015083

NCI-2015-02136

MC1488

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)

Results

• Results available: Yes
• Date Posted: 06/09/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02666950