TerminatedNCT00907517Updated Aug 27, 2018Results posted

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

A Phase 1 interventional study of MK-8776 and Cytarabine in Myelogenous Leukemia, Acute, Leukemia, Lymphocytic, Acute and Leukemia, Lymphoblastic, Acute, Philadelphia-Positive, sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-08-27.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 24
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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 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.

Conditions studied

Myelogenous Leukemia, Acute
Leukemia, Lymphocytic, Acute
Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
Myelogenous Leukemia, Chronic, Aggressive Phase

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In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 24 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.

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Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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)].
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.

Exclusion criteria

Exclusion Criteria:

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.
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.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 24 participants (actual)

Study arms

Experimental
MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2
Participants 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).
Drug: MK-8776 · Drug: Cytarabine
Experimental
MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2
Participants 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).
Drug: MK-8776 · Drug: Cytarabine
Experimental
MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2
Participants 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).
Drug: MK-8776 · Drug: Cytarabine
Experimental
MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2
Participants 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).
Drug: MK-8776 · Drug: Cytarabine
Experimental
MK-8776 140 mg + Cytarabine 2 g/m^2
Participants 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).
Drug: MK-8776 · Drug: Cytarabine

Interventions

DrugMK-8776
IV infusion
Also known as: SCH 900776
DrugCytarabine
IV infusion
Also known as: Generic: ara-C and cytosine arabinoside, Cytosar-U®

What researchers measure

Primary outcomes

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.
Time frame: Throughout Cycle 1 (Up to 6 weeks)
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.
Time frame: Up to 45 days after last dose of study treatment (Up to 180 days)
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.
Time frame: Up to 135 days

Results

Posted Jan 25, 2017

Participant flow

Participant flow — Overall Study
Milestone	MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 140 mg + Cytarabine 2 g/m^2
Started	3	3	6	6	6
Completed	0	0	2	2	1
Not completed	3	3	4	4	5
Withdrew: Progressive disease	3	3	4	4	4
Withdrew: Symptomatic deterioration	0	0	0	0	1

Outcome measures

PrimaryNumber 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.

Time frame:: Throughout Cycle 1 (Up to 6 weeks)
Reported as:: Number · Participants

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Participants	MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 140 mg + Cytarabine 2 g/m^2
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)	0	0	0	0	3

PrimaryNumber 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.

Time frame:: Up to 45 days after last dose of study treatment (Up to 180 days)
Reported as:: Number · Participants

Number of Participants Who Experienced an Adverse Event (AE)
Participants	MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 140 mg + Cytarabine 2 g/m^2
Number of Participants Who Experienced an Adverse Event (AE)	3	3	6	6	6

PrimaryNumber of Participants Who Discontinued Study Treatment Due to an AE

Time frame:: Up to 135 days
Reported as:: Number · Participants

Number of Participants Who Discontinued Study Treatment Due to an AE
Participants	MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 140 mg + Cytarabine 2 g/m^2
Number of Participants Who Discontinued Study Treatment Due to an AE	0	0	0	0	0

Adverse events

Collected over Up to 45 days after last dose of study treatment (Up to 180 days). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2	—	0/3 (0%)	3/3 (100%)
MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2	—	0/3 (0%)	3/3 (100%)
MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2	—	1/6 (16.7%)	6/6 (100%)
MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2	—	2/6 (33.3%)	6/6 (100%)
MK-8776 140 mg + Cytarabine 2 g/m^2	—	1/6 (16.7%)	6/6 (100%)

Most frequent serious events

Showing 10 of 12

Most frequent serious events
Event	MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 140 mg + Cytarabine 2 g/m^2
FEBRILE NEUTROPENIABlood and lymphatic system disorders	0/3	0/3	0/6	0/6	1/6
GASTRITISGastrointestinal disorders	0/3	0/3	0/6	0/6	1/6
NAUSEAGastrointestinal disorders	0/3	0/3	0/6	1/6	0/6
VOMITINGGastrointestinal disorders	0/3	0/3	0/6	1/6	0/6
FUNGAL INFECTIONInfections and infestations	0/3	0/3	1/6	0/6	0/6
PNEUMONIAInfections and infestations	0/3	0/3	0/6	1/6	0/6
PNEUMONIA FUNGALInfections and infestations	0/3	0/3	1/6	0/6	0/6
SUBDURAL HAEMATOMAInjury, poisoning and procedural complications	0/3	0/3	0/6	1/6	0/6
HEADACHENervous system disorders	0/3	0/3	0/6	1/6	0/6
RENAL FAILURE ACUTERenal and urinary disorders	0/3	0/3	0/6	1/6	0/6

Most frequent other events

Showing 10 of 164

Most frequent other events
Event	MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 140 mg + Cytarabine 2 g/m^2
FEBRILE NEUTROPENIABlood and lymphatic system disorders	1/3	2/3	5/6	3/6	5/6
NAUSEAGastrointestinal disorders	1/3	1/3	4/6	5/6	5/6
HYPERTENSIONVascular disorders	0/3	0/3	0/6	5/6	0/6
PERICARDIAL EFFUSIONCardiac disorders	0/3	2/3	0/6	0/6	0/6
DIARRHOEAGastrointestinal disorders	1/3	1/3	4/6	4/6	2/6
VOMITINGGastrointestinal disorders	1/3	1/3	3/6	4/6	1/6
MUCOSAL INFLAMMATIONGeneral disorders	2/3	1/3	2/6	4/6	0/6
OEDEMA PERIPHERALGeneral disorders	0/3	2/3	1/6	2/6	1/6
HYPERBILIRUBINAEMIAHepatobiliary disorders	2/3	1/3	2/6	1/6	2/6
CANDIDIASISInfections and infestations	2/3	0/3	1/6	2/6	0/6

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 140 mg + Cytarabine 2 g/m^2	Total
Mean	59.3 ± 9.1	55.7 ± 1.5	44.2 ± 14.2	57.5 ± 18.3	56.3 ± 13.5	53.9 ± 14.0

Sex: Female, Male
Sex: Female, Male(Participants)	MK-8776 10 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 20 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 40 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 56 mg/m^2 + Cytarabine 2 g/m^2	MK-8776 140 mg + Cytarabine 2 g/m^2	Total
Female	1	3	2	4	3	13
Male	2	0	4	2	3	11

Study locations

No study locations are listed for this record.

References and documents

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 ↗

Individual participant data

Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 27, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00907517
Lead sponsor: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: May 22, 2009
Start date: Jul 29, 2009
Primary completion: Jun 13, 2011
Completion: Jun 13, 2011
Results posted: Jan 25, 2017
Last update: Aug 27, 2018

Study contacts

Medical Director

study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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