Chronic Myelomonocytic LeukemiaPhase 1NCT02649764

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

A Phase 1 study testing Cytarabine, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Chronic Myelomonocytic Leukemia and Recurrent Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Chronic Myelomonocytic Leukemia, Recurrent Acute Myeloid Leukemia, Recurrent High Risk Myelodysplastic Syndrome
What is being tested?: Cytarabine, Fludarabine Phosphate and Laboratory Biomarker Analysis
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 1 siteUnited States
Study dates: 4 May 2016to 12 Jul 2022
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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%)

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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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

M D Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

Official title: 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)

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.

Read the detailed description

PRIMARY OBJECTIVES:

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:

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.

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.

Conditions: Chronic Myelomonocytic Leukemia, Recurrent Acute Myeloid Leukemia, Recurrent High Risk Myelodysplastic Syndrome, Refractory Acute Myeloid Leukemia, Refractory High Risk Myelodysplastic Syndrome
Being tested: Cytarabine, Fludarabine Phosphate, Laboratory Biomarker Analysis, Prexasertib
Medical subject headings: Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CytarabineDrug
Also called .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
Given IV
Fludarabine PhosphateDrug
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
PrexasertibDrug
Also called LY2606368
Given IV

Study groups in NCT02649764
Study group	Role	What they receive
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. Receives: Drug: Cytarabine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Prexasertib

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of dose-limiting toxicities of prexasertib in combination with cytarabine and fludarabine
Will be determined.
Measured: 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])
Will be determined.
Measured: Up to 2 years
Duration of response
Will be determined.
Measured: Up to 2 years
Disease-free survival
Will be determined.
Measured: Up to 2 years
Overall survival
Will be determined.
Measured: Up to 2 years
Total and phosphorylated biomarker levels in acute myeloid leukemia cells
Measured by flow cytometry and/or Western blot.
Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 May 201612 Jul 2022

First posted7 Jan 2016 (estimated)
Study start4 May 2016
Primary completion12 Jul 2022
Study completion12 Jul 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Chronic Myelomonocytic LeukemiaStudies of the same condition, open and under way.
More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02649764
Sponsor's protocol ID: 2015-0665
Other IDs: NCI-2016-00225, 2015-0665
Status last verified: Oct 2023
First submitted: 5 Jan 2016
Last updated: 4 Oct 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
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Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
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RecruitingPhase 1
Phase 1 Study of 6MW5311 in Adults With Relapsed or Refractory Blood Cancers
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Active, not recruitingPhase 2
Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
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RecruitingPhase 2
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All Chronic Myelomonocytic Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT02649764
Acronym / sponsor ID: 2015-0665
Conditions: Chronic Myelomonocytic Leukemia, Recurrent Acute Myeloid Leukemia, Recurrent High Risk Myelodysplastic Syndrome, Refractory Acute Myeloid Leukemia, Refractory High Risk Myelodysplastic Syndrome
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: M.D. Anderson Cancer CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 4 May 2016 (actual)
Primary completion: 12 Jul 2022 (actual)
Study completion: 12 Jul 2022 (actual)
First posted: 7 Jan 2016 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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:

To determine the complete response (CR), CR with incomplete count recovery (CRi), morphologic leukemia free state (MLFS) and partial response (PR) rates.

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).

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (fludarabine phosphate, cytarabine, prexasertib)	Experimental	Drug: Cytarabine, Drug: Fludarabine Phosphate, Other: Laboratory Biomarker Analysis, Drug: PrexasertibPatients =/< 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CytarabineAlso: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinoneGiven IV	Drug	Treatment (fludarabine phosphate, cytarabine, prexasertib)
Fludarabine PhosphateAlso: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, FludaraGiven IV	Drug	Treatment (fludarabine phosphate, cytarabine, prexasertib)
Laboratory Biomarker AnalysisCorrelative studies	Other	Treatment (fludarabine phosphate, cytarabine, prexasertib)
PrexasertibAlso: LY2606368Given IV	Drug	Treatment (fludarabine phosphate, cytarabine, prexasertib)

Primary outcome

Incidence of dose-limiting toxicities of prexasertib in combination with cytarabine and fludarabine
Time frame: Up to 28 days
Will be determined.

5 secondary outcomes

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
Duration of response
Time frame: Up to 2 years
Disease-free survival
Time frame: Up to 2 years
Overall survival
Time frame: Up to 2 years
Total and phosphorylated biomarker levels in acute myeloid leukemia cells
Time frame: Up to 2 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2023.
University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.

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Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gautam Borthakur principal investigator

M.D. Anderson Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicities of prexasertib in combination with cytarabine and fludarabine (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02649764.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2023.