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Myelogenous Leukemia, AcutePhase 1NCT00907517

Study of SCH 900776 (MK-8776) With and Without Cytarabine in Participants With Acute Leukemias (P05247)

A Phase 1 study testing MK-8776 and Cytarabine in people with Myelogenous Leukemia, Acute and Leukemia, Lymphocytic, Acute, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study of SCH 900776 (MK-8776) will evaluate its safety and tolerability when given in combination with cytarabine to participants with acute leukemias. Participants in the Dose-Escalation Part will be enrolled in cohorts that will receive sequentially higher doses of MK-8776 in combination with standard doses of… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MK-8776 and Cytarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
No sites listed yet
Study dates
29 Jul 2009to 13 Jun 2011
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Must have a histologically or cytologically confirmed diagnosis of relapsed and/or refractory acute leukemia, including:
  • acute myelogenous leukemia (AML), including AML arising from myelodysplasia (MDS) or myeloproliferative disorder (MPD);
  • acute lymphocytic leukemia, including Philadelphia chromosome-positive (Ph+) ALL (Dose-Escalation Part only);
  • chronic myelogenous leukemia (CML) in accelerated phase (AP) or blast crisis (BC) of either myeloid or lymphoid origin (Dose-Escalation Part only);
  • treatment-related high-grade MDS (i.e. refractory anemia with excess blasts in transformation [RAEBT]);
  • MPD in transformation [eg, CMMoL-T (5%-19% blasts)].
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  • Must have recurred or progressed following standard therapy or failed standard therapy, or have disease for which no standard therapy currently exists.
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Females of childbearing potential must have a negative pregnancy test within 5 days prior to first dose of cytarabine.
  • Females of childbearing potential and males whose sexual partner is of childbearing potential must agree to abstain from sexual intercourse or to use an acceptable method of contraception during the study and for 90 days following the last dose of study treatment.
  • Must have adequate renal function as evidenced by a serum creatinine level <=1.5 x upper limit of normal (ULN) or a calculated creatinine clearance >=60 mL/min.
  • Participants, except ones with known Gilbert's Syndrome, must have adequate hepatic function as evidenced by a serum bilirubin level <=1.5 mg/dL AND serum levels of aspartate and alanine aminotransferase (AST/ALT) <=5 x the ULN for the reference laboratory.
  • Must have adequate cardiac function with a left ventricular ejection fraction (LVEF) of >=45% (echocardiogram or multiple-gated acquisition [MUGA] scan).
  • Must be recovered from the effects of any prior surgery, radiotherapy, or systemic antineoplastic therapy.
  • Participants who are refractory to or relapsed after prior allogeneic or autologous stem cell transplant are eligible.

Who cannot join

  • Must not have known hypersensitivity to MK-8776 or cytarabine or to any of their excipients or have received therapy with another Checkpoint kinase 1 (CHK1) inhibitor.
  • Must not have persistent, unresolved Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v 3.0) ≥ Grade 2 drug-related toxicity (except alopecia, erectile impotence, hot flashes, decreased libido, hematologic toxicity) associated with previous treatment.
  • Must not have known human immunodeficiency virus (HIV), hepatitis B or hepatitis C, or have a known history of liver cirrhosis or active alcohol abuse.
  • Must not be New York Heart Association (NYHA) Class III (has marked limitation in activity due to symptoms, even during less than ordinary activity [e.g. walking short distances >20-100 m]; is comfortable only at rest) or Class IV (has severe limitations; experiences symptoms even while at rest; mostly bed bound).
  • Must not have undergone major surgery within 3 weeks prior to first study drug administration after enrollment.
  • Must not have known active central nervous system (CNS) or leptomeningeal leukemia.
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  • Must not have received radiation therapy within 2 weeks prior to first study treatment administration after enrollment or radiation therapy to >25% of bone marrow.
  • Must not have received more than 4 prior induction regimens.
  • Must not have a peripheral blast count ≥50,000/mm^3.
  • Must not have active, uncontrolled graft versus host disease (GVHD) post-allogeneic stem cell transplant.
  • Must not have had any of the following within 6 months prior to first study treatment administration after enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or seizure disorder.
  • Must not have a known bleeding diathesis, e.g. hemophilia, or disseminated intravascular coagulation.
  • Must not have an active, uncontrolled infection.
  • Must not have a history of cytarabine-related neurotoxicity.
  • Must not have a baseline corrected QT (QTc) interval >470 msec (i.e. CTCAE v 3.0 Grade ≥2).
  • Must not currently be a smoker and/or must not be likely to smoke during the study.
  • Females must not be breast-feeding, pregnant, or intend to become pregnant.

About this study

Official title: A Phase 1 Dose-Escalation Study of SCH 900776 in Combination With Cytarabine in Subjects With Acute Leukemias (Protocol No. P05247)

This study of SCH 900776 (MK-8776) will evaluate its safety and tolerability when given in combination with cytarabine to participants with acute leukemias. Participants in the Dose-Escalation Part will be enrolled in cohorts that will receive sequentially higher doses of MK-8776 in combination with standard doses of cytarabine. Only one combination treatment cycle of approximately 4 to 6 weeks is anticipated, but participants may receive additional cycles if clinically indicated after discussion between the Investigator and the Sponsor. The recommended combination doses for a Phase 2 trial (RP2D) will be determined based on safety and biological activity. Up to 10 to 15 additional participants will be studied at the combination RP2D.

Being tested
MK-8776, Cytarabine
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Accelerated Phase

What participants receive

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

  • MK-8776Drug

    Also called SCH 900776

    IV infusion

  • CytarabineDrug

    Also called Generic: ara-C and cytosine arabinoside, Cytosar-U®

    IV infusion

Study groups in NCT00907517
Study groupRoleWhat they receive
MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2ExperimentalParticipants received MK-8776 10 mg/m^2 intravenously (IV) on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m^2 IV via 72-hour continuous intravenous infusion (CIV) on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).
Receives: Drug: MK-8776; Drug: Cytarabine
MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2ExperimentalParticipants received MK-8776 20 mg/m^2 IV on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m^2 IV via 72-hour CIV on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).
Receives: Drug: MK-8776; Drug: Cytarabine
MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2ExperimentalParticipants received MK-8776 40 mg/m^2 IV on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m^2 IV via 72-hour CIV on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).
Receives: Drug: MK-8776; Drug: Cytarabine
MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2ExperimentalParticipants received MK-8776 56 mg/m^2 IV on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m^2 IV via 72-hour CIV on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).
Receives: Drug: MK-8776; Drug: Cytarabine
MK-8776 140 mg + Cytarabine 2 g/m^2ExperimentalParticipants received MK-8776 140 mg flat dose IV on Days 2 and 3 and again on Days 11 and 12 PLUS cytarabine 2 g/m^2 IV via 72-hour CIV on Days 1 through 3 and repeated on Days 10 through 12 of a treatment cycle. The duration of one treatment cycle was to be approximately 4 to 6 weeks (until hospital discharge).
Receives: Drug: MK-8776; Drug: Cytarabine

What is being measured

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

  1. Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

    Toxicity was assessed according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v 3.0). DLTs in Cycle 1 consisted of any of the following: 1) Selected Grade 4 drug-related nonhematologic toxicities, 2) Selected Grade 3 drug-related nonhematologic toxicities that do not resolve to ≤ Grade 2 within 48 hours: Neurotoxicity of any duration, Nephrotoxicity of any duration, QT interval corrected by Fridericia (QTcF) prolongation of any duration, 3) Inability to administer Day 10 cytarabine therapy due to ongoing, uncontrolled serious or life-threatening toxicity. The number of participants who experienced a DLT during Cycle 1 is summarized.

    Measured: Throughout Cycle 1 (Up to 6 weeks)

  2. Number of Participants Who Experienced an Adverse Event (AE)

    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to this study treatment. The number of participants who experienced an AE is summarized.

    Measured: Up to 45 days after last dose of study treatment (Up to 180 days)

  3. Number of Participants Who Discontinued Study Treatment Due to an AE

    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to this study treatment. The number of participants who discontinued study treatment due to an AE is summarized.

    Measured: Up to 135 days

Timeline

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

  1. First posted22 May 2009 (estimated)
  2. Study start29 Jul 2009
  3. Primary completion13 Jun 2011
  4. Study completion13 Jun 2011

Resources

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00907517
Sponsor's protocol ID
P05247
Other IDs
MK-8776-001
Status last verified
Jul 2018
First submitted
21 May 2009
Last updated
27 Aug 2018
Data monitoring committee
No
Individual data sharing
Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Karp JE, Thomas BM, Greer JM, Sorge C, Gore SD, Pratz KW, Smith BD, Flatten KS, Peterson K, Schneider P, Mackey K, Freshwater T, Levis MJ, McDevitt MA, Carraway HE, Gladstone DE, Showel MM, Loechner S, Parry DA, Horowitz JA, Isaacs R, Kaufmann SH. Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias. Clin Cancer Res. 2012 Dec 15;18(24):6723-31. doi: 10.1158/1078-0432.CCR-12-2442. Epub 2012 Oct 23.

    PubMed 23092873

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-8776 and Cytarabine in people with Myelogenous Leukemia, Acute and Leukemia, Lymphocytic, Acute, run by Merck Sharp & Dohme LLC.

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 15 inclusion and 17 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: stopped early, as of the sponsor's last update on 27 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

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?

Yes. Results are posted in the registry (first posted 25 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) (time frame: Throughout Cycle 1 (Up to 6 weeks)). The study lists 3 primary outcomes in all. 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 NCT00907517, which also lists 1 linked publication.

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 27 Aug 2018.

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