- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02649764
Prexasertib (LY2606368), Cytarabine, and Fludarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Phase 1 A/B Study of LY2606368 in Combination With Cytarabine and Fludarabine in Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HRMDS)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety and toxicity profile of combination therapy of prexasertib (LY2606368), fludarabine and cytarabine in patients with relapsed or refractory (first or second salvage) acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HRMDS).
SECONDARY OBJECTIVES:
I. To determine the complete response (CR), CR with incomplete count recovery (CRi), morphologic leukemia free state (MLFS) and partial response (PR) rates.
II. To determine the duration of response. III. To determine the disease-free survival. IV. To determine the overall survival with combination therapy of LY2606368, fludarabine and cytarabine in patients with relapsed or refractory AML/HRMDS.
V. To determine the correlative studies including but not limited to total and phosphor histone (H2AX), checkpoint kinase-2 (Chk1), checkpoint kinase-2 (Chk2), ras protein specific guanine nucleotide releasing factor 1 (Cdc25), retinoblastoma-associated protein (Rb), cyclin-dependent kinase (CDK), protein kinase B (AKT) in AML cells by flow cytometry and/or Western blot.
OUTLINE: This is a dose-escalation study of prexasertib (LY2606368).
Patients =/< 65 years of age: receive fludarabine intravenously (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.
After completion of study treatment, patients in remission who do not start new treatment are followed up every 2-3 months for up to 2 years.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
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Houston, Texas, United States, 77030
- M D Anderson Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (fludarabine phosphate, cytarabine, prexasertib)
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.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of dose-limiting toxicities of prexasertib in combination with cytarabine and fludarabine
Time Frame: Up to 28 days
|
Will be determined.
|
Up to 28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rates (complete response [CR], CR with incomplete count recovery [CRi], morphologic leukemia free state [MLFS], and partial response [PR])
Time Frame: Up to 2 years
|
Will be determined.
|
Up to 2 years
|
Duration of response
Time Frame: Up to 2 years
|
Will be determined.
|
Up to 2 years
|
Disease-free survival
Time Frame: Up to 2 years
|
Will be determined.
|
Up to 2 years
|
Overall survival
Time Frame: Up to 2 years
|
Will be determined.
|
Up to 2 years
|
Total and phosphorylated biomarker levels in acute myeloid leukemia cells
Time Frame: Up to 2 years
|
Measured by flow cytometry and/or Western blot.
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Gautam Borthakur, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
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 (Estimated)
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 Attributes
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Myelodysplastic-Myeloproliferative Diseases
- Chronic Disease
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Recurrence
- Preleukemia
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protein Kinase Inhibitors
- Fludarabine
- Fludarabine phosphate
- Cytarabine
- Prexasertib
Other Study ID Numbers
- 2015-0665 (Other Identifier: M D Anderson Cancer Center)
- NCI-2016-00225 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
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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