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

NCT02666950 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC1488NCI-2015-02136P30CA015083
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CR or CRi) Per the National Comprehensive Cancer Network (NCCN) Guidelines or According to Specific Criteria From Expert Panels

  Complete response rate will be evaluated over all courses of study treatment. The proportion of CR/CRi responses will be estimated by the number of CR/CRi responses divided by the total number of evaluable patients.

  Up to 17 months

Secondary Outcomes (6)

• Clinical Benefit as Measured by the Number of Patients Who Were Not RBC Transfusion-dependent Post-Baseline

  Up to 17 months

• Duration of Response

  Up to 17 months

• Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment

  Up to 30 days post-treatment

• Overall Survival

  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

  Up to 17 months

Other Outcomes (8)

• Change in Biomarker Levels

  Baseline to up to 113 days (after course 4)

• Change in Patients' Reported Outcomes as Assessed by the Brief Fatigue Inventory (BFI)

  Baseline to 2 years

• Change in QOL as Assessed by the European Organization for Treatment and Research of Cancer Quality of Life Questionnaire Core Questionnaire 30

  Baseline to 2 years

Study Arms (2)

Arm B (cytarabine and WEE1 inhibitor AZD1775

EXPERIMENTAL

Patients receive cytarabine and WEE1 inhibitor AZD1775 as in Arm A.

Drug: Cytarabine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: WEE1 Inhibitor AZD1775

Arm C (WEE inhibitor AZD1775)

EXPERIMENTAL

Patients receive WEE inhibitor AZD1775 PO daily on days 1-5, 8-12, 15-19, and 22-26.

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: WEE1 Inhibitor AZD1775

Interventions

Cytarabine DRUG

Given SC

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Arm B (cytarabine and WEE1 inhibitor AZD1775

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm B (cytarabine and WEE1 inhibitor AZD1775; Arm C (WEE inhibitor AZD1775)

Pharmacological Study OTHER

Correlative studies

Arm B (cytarabine and WEE1 inhibitor AZD1775; Arm C (WEE inhibitor AZD1775)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm B (cytarabine and WEE1 inhibitor AZD1775; Arm C (WEE inhibitor AZD1775)

Questionnaire Administration OTHER

Ancillary studies

Arm B (cytarabine and WEE1 inhibitor AZD1775; Arm C (WEE inhibitor AZD1775)

WEE1 Inhibitor AZD1775 DRUG

Given PO

Also known as: AZD-1775, AZD1775, MK-1775, MK1775

Arm B (cytarabine and WEE1 inhibitor AZD1775; Arm C (WEE inhibitor AZD1775)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Chromosome 5q Deletion Syndrome; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid, Acute

Interventions

Cytarabine; adavosertib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Lisa Sproat, M.D.
• Organization: Mayo Clinic

Sproat.Lisa@mayo.edu

480/301-8000

Study Officials

• Raoul Tibes

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 28, 2016
• Study Start: May 5, 2017
• Primary Completion: September 25, 2018
• Study Completion: October 17, 2018
• Last Updated: September 6, 2019
• Results First Posted: September 6, 2019

Record last verified: 2018-11

Locations

US (1)