Prexasertib (LY2606368), Cytarabine, and Fludarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

NCT02649764 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2015-0665NCI-2016-00225
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and determine the best dose of prexasertib (LY2606368) when given together with cytarabine and fludarabine in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has returned after a period of improvement or no longer responds to treatment. Prexasertib (LY2606368) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and fludarabine, 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. Giving prexasertib (LY2606368) together with cytarabine and fludarabine may work better in treating patients with acute myeloid leukemia or myelodysplastic syndrome.

Conditions

Chronic Myelomonocytic Leukemia; Recurrent Acute Myeloid Leukemia; Recurrent High Risk Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Refractory High Risk Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities of prexasertib in combination with cytarabine and fludarabine

  Will be determined.

  Up to 28 days

Secondary Outcomes (5)

• Response rates (complete response [CR], CR with incomplete count recovery [CRi], morphologic leukemia free state [MLFS], and partial response [PR])

  Up to 2 years

• Duration of response

  Up to 2 years

• Disease-free survival

  Up to 2 years

• Overall survival

  Up to 2 years

• Total and phosphorylated biomarker levels in acute myeloid leukemia cells

  Up to 2 years

Study Arms (1)

Treatment (fludarabine phosphate, cytarabine, prexasertib)

EXPERIMENTAL

Patients =/\< 65 years of age: receive fludarabine IV over approximately 2 hours on days 1-4, cytarabine IV over 4 hours on days 1-4, and prexasertib (LY2606368) IV over approximately 2 hours on days 1, 3, and 4 or on days 1-4. Patients \> 65 years of age: receive fludarabine IV over approximately 2 hours on days 1-3, cytarabine IV over 4 hours on days 1-3, and prexasertib (LY2606368) IV over approximately 2 hours on days 1, 3, and 4 or on days 1-4. Treatment for both age groups repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cytarabine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Prexasertib

Interventions

Cytarabine DRUG

Given IV

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, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (fludarabine phosphate, cytarabine, prexasertib)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (fludarabine phosphate, cytarabine, prexasertib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (fludarabine phosphate, cytarabine, prexasertib)

Prexasertib DRUG

Given IV

Also known as: LY2606368

Treatment (fludarabine phosphate, cytarabine, prexasertib)

Eligibility Criteria

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

You may qualify if:

• All patients with histologically or cytologically confirmed relapsed or refractory acute myeloid leukemia (AML) (except acute promyelocytic leukemia) or relapsed or refractory high-risk myelodysplastic syndrome (HRMDS) (intermediate 2 \[Int-2\] or higher risk by International Prognostic Scoring System \[IPSS\]); patients with chronic myelomonocytic leukemia (CMML) can be enrolled if they can be classified as HRMDS using MDS criteria; patients should not have received more than one salvage therapy; second induction regimen or stem cell transplant in remission will be considered salvage therapy; refractory subjects, up to second consecutive salvage
• Patients must have a performance status of 0-2 (Eastern Cooperative Oncology Group \[ECOG\] scale)
• Serum creatinine less than or equal to 1.3 mg/dL and/or creatinine clearance \> 40 mL/min
• Bilirubin less than or equal to 1.5 mg/dl (unless due to Gilbert's syndrome)
• Serum glutamic-oxaloacetic transaminase (SGOT)/aspartate transaminase (AST) or serum glutamate pyruvate transaminase (SGPT)/alanine transferase (ALT) less than or equal to 2.5 X the upper limit of normal (ULN) for the reference lab
• Patients must have normal cardiac ejection fraction (left ventricular ejection fraction \[LVEF\] \>/= 45%)
• Corrected QT (QTc) interval =/\< 470 msecs, no familial history of QTc prolongation or ventricular arrhythmias
• Female patients must not be pregnant or lactating; female patients of childbearing potential (including those \< 1 year post-menopausal) and male patients must agree to use contraception
• Patients who have received prior stem cell transplantation will be allowed to enroll as long as prior transplantation has been at least 3 months before enrollment in the trial and any transplant related toxicities have subsided to grade 1 or less

You may not qualify if:

• Patients must not have untreated or uncontrolled life-threatening infection
• Patients must not have been treated with CHK1/2 inhibitors
• Patients must not have received chemotherapy and/or radiation therapy within 2 weeks of start of protocol treatment; hydroxyurea is allowed up to 48 hours prior to starting therapy in the setting of rapidly proliferating disease
• Patients must not have received an investigational anti-cancer drug within two weeks of start of protocol treatment
• Patients must not have active central nervous system leukemia; patients with history of central nervous system (CNS) leukemia with no evidence of active CNS disease may be enrolled; maintenance intrathecal chemotherapy for adequately treated CNS involvement with leukemia is allowed with approval from the study supporter
• Patients must not have significant cardiac co-morbidity including: history of acute coronary syndromes (including myocardial infarction and unstable angina) within 12 months; coronary angioplasty or stenting within 6 months; history or evidence of current \>/= class III congestive heart failure as defined by the New York Heart Association (NYHA); patients with intra-cardiac defibrillators or permanent pacemakers

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute

Interventions

Cytarabine; fludarabine phosphate; prexasertib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; 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

Study Officials

• Gautam Borthakur

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2016
• First Posted: January 7, 2016
• Study Start: May 4, 2016
• Primary Completion: July 12, 2022
• Study Completion: July 12, 2022
• Last Updated: October 4, 2023

Record last verified: 2023-10

Locations

US (1)